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Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001.

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Immunobiology: The Immune System in Health and Disease. 5th edition.

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In the context of immunoglobulins, α is the type of heavy chain in IgA.

α:β T cell

see T cell.

α:β T-cell receptor

see T-cell receptor.

ABO blood group system

The ABO blood group system antigens are expressed on red blood cells. They are used for typing human blood for transfusion. Individuals who do not express A or B antigens on their red blood cells naturally form antibodies that interact with them.


The removal of antibodies specific for one antigen from an antiserum to render it specific for another antigen or antigens is called absorption.

Accessory effector cells

Accessory effector cells in adaptive immunity are cells that aid in the response but do not directly mediate specific antigen recognition. They include phagocytes, mast cells, and NK cells.

acquired immune deficiency syndrome

The acquired immune deficiency syndrome AIDS is a disease caused by infection with the human immunodeficiency virus (HIV-1). AIDS occurs when an infected patient has lost most of his or her CD4 T cells, so that infections with opportunistic pathogens occur.

Acquired immune response

see adaptive immune response.

active immunization

Immunization with antigen is called active immunization to distinguish it from the transfer of antibody to an unimmunized individual, which is called passive immunization.

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia is a highly aggressive, undifferentiated form of lymphoid malignancy derived from a progenitor cell that is thought to be able to give rise to both T and B lineages of lymphoid cells. Most of these leukemias show partial differentiation toward the B-cell lineage (so called B-ALL) whereas a minority show features of T cells (T-ALL).

Acute-phase proteins

Acute-phase proteins are found in the blood shortly after the onset of an infection. These proteins participate in early phases of host defense against infection. An example is the mannan-binding lectin.

acute-phase response

The acute-phase response is a change in the blood that occurs during early phases of an infection. It includes the production of acute-phase proteins and also of cellular elements.

adaptive immune response

The adaptive immune response or adaptive immunity is the response of antigen-specific lymphocytes to antigen, including the development of immunological memory. Adaptive immune responses are generated by clonal selection of lymphocytes. Adaptive immune responses are distinct from innate and nonadaptive phases of immunity, which are not mediated by clonal selection of antigen-specific lymphocytes. Adaptive immune responses are also known as acquired immune responses.

adaptor proteins

The adaptor proteins are key linkers between receptors and downstream members of signaling pathways. These proteins are functionally heterogeneous, but all use a similar domain, known as an SH2 domain, as the means of interacting with the phoshotyrosine residues generated by the receptor-associated tyrosine kinases. The protein known as Vav is an adaptor protein of this type.


The adenoids are mucosal-associated lymphoid tissues located in the nasal cavity.

adenosine deaminase deficiency

The enzyme defect adenosine deaminase deficiency leads to the accumulation of toxic purine nucleosides and nucleotides, resulting in the death of most developing lymphocytes within the thymus. It is a cause of severe combined immunodeficiency.

Adhesion molecules

Adhesion molecules mediate the binding of one cell to other cells or to extracellular matrix proteins. Integrins, selectins, members of the immunoglobulin gene superfamily, and CD44 and related proteins are all adhesion molecules important in the operation of the immune system.


An adjuvant is any substance that enhances the immune response to an antigen with which it is mixed.

Adoptive immunity

Adoptive immunity is immunity conferred on a naive or irradiated recipient by transfer of lymphoid cells from an actively immunized donor. This is called adoptive transfer or adoptive immunization.

Afferent lymphatic vessels

Afferent lymphatic vessels drain fluid from the tissues and carry macrophages and dendritic cells from sites of infection in most parts of the body to the lymph nodes.


Affinity is the strength of binding of one molecule to another at a single site, such as the binding of a monovalent Fab fragment of antibody to a monovalent antigen. See also avidity.

Affinity chromatography

Affinity chromatography is the purification of a substance by means of its affinity for another substance immobilized on a solid support. For example, an antigen can be purified by affinity chromatography on a column of beads to which specific antibody molecules are covalently linked.

Affinity maturation

Affinity maturation refers to the increase in the affinity for the specific antigen of the antibodies produced during the course of a humoral immune response. It is particularly prominent in secondary and subsequent immunizations.


see X-linked agammaglobulinemia (XLA).


Agglutination is the clumping together of particles, usually by antibody molecules binding to antigens on the surfaces of adjacent particles. Such particles are said to agglutinate. When the particles are red blood cells, the phenomenon is called hemagglutination.

Agonist peptides

Agonist peptides are peptide antigens that activate their specific T cells, inducing them to make cytokines and to proliferate. They are thought to differ from antagonist peptides by their ability to induce T-cell receptor dimerization.


see acquired immune deficiency syndrome.


Alleles are variants of a single genetic locus.

Allelic exclusion

Allelic exclusion refers to the fact that in a heterozygous individual, only one of the alternative C-region alleles of the heavy or light chain is expressed in a single B cell and in an immunoglobulin molecule. The term has come to be used more generally to describe the expression of a single receptor specificity in cells with the potential to express two or more receptors.


Allergens are antigens that elicit hypersensitivity or allergic reactions.

Allergic asthma

Allergic asthma is constriction of the bronchial tree due to an allergic reaction to inhaled antigen.

allergic conjunctivitis

The lining of the eye, called the conjunctiva, manifests allergic conjunctivitis in sensitized individuals exposed to allergens.

allergic reaction

An allergic reaction is a response to innocuous environmental antigens, or allergens, due to preexisting antibody or primed T cells. There are various immune mechanisms of allergic reactions, but the most common is the binding of allergen to IgE antibody on mast cells, which causes asthma, hay fever, and other common allergic reactions.

Allergic rhinitis

Allergic rhinitis is an allergic reaction in the nasal mucosa, also known as hay fever, that causes runny nose, sneezing, and tears.


Allergy is a symptomatic reaction to a normally innocuous environmental antigen. It results from the interaction between the antigen and antibody or primed T cells produced by earlier exposure to the same antigen.


Alloantigens are classically defined as polymorphisms at the MHC locus; they stimulate intense reactions to allografted tissues, hence their naming.


Two individuals or two mouse strains that differ at the MHC are said to be allogeneic. The term can also be used for allelic differences at other loci. Rejection of grafted tissues from unrelated donors usually results from T-cell responses to allogeneic MHC molecules expressed by the grafted tissues. See also syngeneic; xenogeneic.


An allograft is a graft of tissue from an allogeneic or nonself donor of the same species; such grafts are invariably rejected unless the recipient is immunosuppressed.


Alloreactivity describes the stimulation of T cells by MHC molecules other than self; it marks the recognition of allogeneic MHC molecules. Such responses are also called alloreactions.


Allotypes are allelic polymorphisms that can be detected by antibodies specific for the polymorphic gene products; in immunology, allotypic differences in immunoglobulin molecules were important in deciphering the genetics of antibodies.

altered peptide ligand

An altered peptide ligand, or partial agonist, is a peptide, usually closely related to an agonist peptide in amino acid sequence, that induces only a partial response from T cells specific for the agonist peptide.

alternative pathway

The alternative pathway of complement activation is not triggered by antibody, as is the classical pathway of complement activation, but by the binding of complement protein C3b to the surface of a pathogen; it is therefore a feature of innate immunity. The alternative pathway also amplifies the classical pathway of complement activation.

Anaphylactic shock

Anaphylactic shock or systemic anaphylaxis is an allergic reaction to systemically administered antigen that causes circulatory collapse and suffocation due to tracheal swelling. It results from binding of antigen to IgE antibody on connective tissue mast cells throughout the body, leading to the disseminated release of inflammatory mediators.


Anaphylatoxins are small fragments of complement proteins, released by cleavage during complement activation. These small fragments are recognized by specific receptors, and they recruit fluid and inflammatory cells to sites of their release. The fragments C5a, C3a, and C4a are all anaphylatoxins, listed in order of decreasing potency in vivo.

anchor residues

Peptide fragments of antigens are bound to specific MHC class I molecules by anchor residues. These are residues of the peptide that have amino acid side chains that bind into pockets lining the peptide-binding groove of the MHC class I molecule. Each MHC class I molecule binds different patterns of anchor residues, called anchor motifs, giving some specificity to peptide binding. Anchor residues exist but are less obvious for peptides that bind to MHC class II molecules.


Anergy is a state of nonresponsiveness to antigen. People are said to be anergic when they cannot mount delayed-type hypersensitivity reactions to challenge antigens, whereas T cells and B cells are said to be anergic when they cannot respond to their specific antigen under optimal conditions of stimulation.

Antagonist peptides

Antagonist peptides are peptides, usually closely related in sequence to an agonist peptide, that inhibit the response of a cloned T-cell line specific for the agonist peptide.


An antibody is a protein that binds specifically to a particular substance—its antigen. Each antibody molecule has a unique structure that enables it to bind specifically to its corresponding antigen, but all antibodies have the same overall structure and are known collectively as immunoglobulins or Igs. Antibodies are produced by plasma cells in response to infection or immunization, and bind to and neutralize pathogens or prepare them for uptake and destruction by phagocytes.

Antibody combining site

see antigen-binding site.

antibody repertoire

The antibody repertoire or immunoglobulin repertoire describes the total variety of antibodies in the body of an individual.

Antibody-dependent cell-mediated cytotoxicity

Antibody-dependent cell-mediated cytotoxicity (ADCC) is the killing of antibody-coated target cells by cells with Fc receptors that recognize the constant region of the bound antibody. Most ADCC is mediated by NK cells that have the Fc receptor FcγRIII or CD16 on their surface.


An antigen is any molecule that can bind specifically to an antibody. Their name arises from their ability to generate antibodies. However, some antigens do not, by themselves, elicit antibody production; those antigens that can induce antibody production are called immunogens.

antigen display libraries

Both libraries of cDNA clones in expression vectors and bacteriophage libaries encoding random peptide sequences have been used to identify the targets of specific antibodies and, in some cases, of T cells. Such libraries are termed antigen display libraries.

Antigen:antibody complexes

Antigen:antibody complexes are noncovalently associated groups of antigen and antibody molecules that can vary in size from small soluble complexes to large insoluble complexes that precipitate out of solution; they are also known as immune complexes.

antigen-binding site

The antigen-binding site of an antibody, or antibody combining site, is found at the surface of the antibody molecule that makes physical contact with the antigen. Antigen-binding sites are made up of six hypervariable loops, three from the light-chain V region and three from the heavy-chain V region.

antigen-capture assay

In an antigen-capture assay, the antigen binds to a specific antibody, and its presence is detected by a second antibody that must be labeled and directed at a different epitope.

antigenic determinant

An antigenic determinant is the portion of an antigenic molecule that is bound by a given antibody or antigen receptor; it is also known as an epitope.

antigenic drift

Influenza virus varies from year to year by a process of antigenic drift in which point mutations of viral genes cause small differences in the structure of viral surface antigens. Periodically, influenza viruses undergo an antigenic shift through reassortment of their segmented genome with another influenza virus, changing their surface antigens radically. Such antigenic shift variants are not recognized by individuals immune to influenza, so when antigenic shift variants arise, there is widespread and serious disease.

antigenic variation

Many pathogens evade the adaptive immune response by antigenic variation in which new antigens are displayed that are not recognized by antibodies or T cells elicited in earlier infections.

Antigen presentation

Antigen presentation describes the display of antigen as peptide fragments bound to MHC molecules on the surface of a cell; T cells recognize antigen when it is presented in this way.

Antigen-presenting cells

Antigen-presenting cells (APCs) are highly specialized cells that can process antigens and display their peptide fragments on the cell surface together with molecules required for T-cell activation. The main antigen-presenting cells for T cells are dendritic cells, macrophages, and B cells.

Antigen processing

Antigen processing is the degradation of proteins into peptides that can bind to MHC molecules for presentation to T cells. All antigens except peptides must be processed into peptides before they can be presented by MHC molecules.

antigen receptors

T and B lymphocytes collectively bear on their surface highly diverse antigen receptors capable of recognizing a wide diversity of antigens. Each individual lymphocyte bears receptors of a single antigen specificity.

Antigen spreading

see epitope spreading.

Anti-immunoglobulin antibodies

Anti-immunoglobulin antibodies are antibodies against immunoglobulin constant domains, useful for detecting bound antibody molecules in immunoassays and other applications. These can be divided into anti-isotype antibodies made in a different species, anti-allotype antibodies made in the same species against allotypic variants, and anti-idiotype antibodies, made against unique determinants to a single antibody.

Anti-lymphocyte globulin

Anti-lymphocyte globulin is antibody raised in another species against human T cells.


An antiserum: antisera is the fluid component of clotted blood from an immune individual that contains antibodies against the molecule used for immunization. Antisera contain heterogeneous collections of antibodies, which bind the antigen used for immunization, but each has its own structure, its own epitope on the antigen, and its own set of cross-reactions. This heterogeneity makes each antiserum unique.


Bites by poisonous snakes can be treated by identification of the snake and injection of an antivenin specific for that snake’s venom.

Aplastic anemia

Aplastic anemia is a failure of bone marrow stem cells so that formation of all cellular elements of the blood ceases; it can be treated by bone marrow transplantation.


Apoptosis, or programmed cell death, is a form of cell death in which the cell activates an internal death program. It is characterized by nuclear DNA degradation, nuclear degeneration and condensation, and the phagocytosis of cell residua. Proliferating cells frequently undergo apoptosis, which is a natural process in development, and proliferating lymphocytes undergo high rates of apoptosis in development and during immune responses. Apoptosis contrasts with necrosis, death from without, which occurs in situations such as poisoning and anoxia.


The appendix is a gut-associated lymphoid tissue located at the beginning of the colon.

armed effector T cells

In this book, we have termed primed effector T cells armed effector T cells, because these cells can be triggered to perform their effector functions immediately on contact with cells bearing the peptide:MHC complex for which they are specific. They contrast with memory T cells, which need to be activated by antigen-presenting cells to differentiate into effector T cells before they can mediate effector responses.

Arthus reaction

The Arthus reaction is a skin reaction in which antigen is injected into the dermis and reacts with IgG antibodies in the extracellular spaces, activating complement and phagocytic cells to produce a local inflammatory response.

Ascertainment artifact

Ascertainment artifact refers to data that seem to demonstrate some finding, but fail to do so because they are collected from a population that is selected in a biased fashion.

Ataxia telangiectasia

Ataxia telangiectasia is a disease characterized by staggering, multiple disorganized blood vessels, and an immunodeficiency in a protein called ATM, which contains a kinase thought to be important in signaling of double-stranded DNA breaks.

Atopic allergy

Atopic allergy, or atopy, is the increased tendency seen in some people to produce immediate hypersensitivity reactions (usually mediated by IgE antibodies) against innocuous substances.


Pathogens are said to be attenuated when they can grow in their host and induce immunity without producing serious clinical disease.


Antibodies specific for self antigens are called autoantibodies.


A graft of tissue from one site to another on the same individual is called an autograft.

autoimmune diseases

Diseases in which the pathology is caused by adaptive immune responses to self antigens are called autoimmune diseases.

Autoimmune hemolytic anemia

Autoimmune hemolytic anemia is a pathological condition with low levels of red blood cells (anemia), which is caused by autoantibodies that bind red blood cell surface antigens and target the red blood cell for destruction.

autoimmune response

An adaptive immune response directed at self antigens is called an autoimmune response; likewise, adaptive immunity specific for self antigens is called autoimmunity.

autoimmune thrombocytopenic purpura

In the disease autoimmune thrombocytopenic purpura, antibodies against a patient’s platelets are made. Antibody binding to platelets causes them to be taken up by cells with Fc receptors and complement receptors, causing a fall in platelet counts that leads to purpura (bleeding).


Autoreactivity describes immune responses directed at self antigens.


Avidity is the sum total of the strength of binding of two molecules or cells to one another at multiple sites. It is distinct from affinity, which is the strength of binding of one site on a molecule to its ligand.

avidity hypothesis

The avidity hypothesis of T-cell selection in the thymus states that T cells must have a measurable affinity for self MHC molecules in order to mature, but not so great an affinity as to cause activation of the cell when it matures, as this would require that the cell be deleted to maintain self tolerance.


Azathioprine is a potent immunosuppressive drug that is converted to its active form in vivo and then kills rapidly proliferating cells, including lymphocytes responding to grafted tissues.



4-1BB is a member of the TNF receptor family that specifically binds to 4-1BB ligand.

4-1BB ligand

4-1BB ligand (4-1BBL) is a member of the TNF family that binds to 4-1BB.

β barrel

see β sheet.

B cell

A B cell, or B lymphocyte, is one of the two major types of lymphocyte. The antigen receptor on B lymphocytes, usually called the B-cell receptor, is a cell-surface immunoglobulin. On activation by antigen, B cells differentiate into cells producing antibody molecules of the same antigen specificity as this receptor. B cells are divided into two classes. B-1 cells, also known as CD5 B cells, are a class of atypical, self-renewing B cells found mainly in the peritoneal and pleural cavities in adults. They have a far less diverse repertoire of receptors than do B-2 cells, also known as conventional B cells, which are generated in the bone marrow throughout life, emerging to populate the blood and lymphoid tissues.

β sheet

A β sheet is one of the fundamental structural building blocks of proteins, consisting of adjacent, extended strands of amino acids (β strands) that are bonded together by interactions between backbone amide and carbonyl groups. β Sheets can be parallel, in which case the adjacent strands run in the same direction, or antiparallel, where adjacent strands run in opposite directions. All immunoglobulin domains are made up of antiparallel β-sheet structures. A β barrel or a β sandwich is another way of describing the structure of the immunoglobulin domain.


The light chain of the MHC class I proteins is called β2-microglobulin. It binds noncovalently to the heavy or α chain.

B7 molecules

The major T-cell co-stimulatory molecules are the B7 molecules , B7.1 (CD80) and B7.2 (CD86). They are closely related members of the immunoglobulin gene superfamily and both bind to the CD28 molecule on T cells. They are expressed differentially on various antigen-presenting cell types. We use the term B7 molecules to refer to both B7.1 and B7.2.


Many infectious diseases are caused by bacteria, which are prokaryotic microorganisms that exist as many different species and strains. Bacteria can live on body surfaces, in extracellular spaces, in cellular vesicles, or in the cytosol, and different bacterial species cause distinctive infectious diseases.


see bronchial-associated lymphoid tissue.

Bare lymphocyte syndrome

Bare lymphocyte syndrome is an immunodeficiency disease in which MHC class II molecules are not expressed on cells as a result of one of several different regulatory gene defects. Patients with bare lymphocyte syndrome are severely immunodeficient and have few CD4 T cells. In MHC class I deficiency, or bare lymphocyte syndrome (MHC class I), the most common defect is mutation in either TAP1 or TAP2.


Basophils are white blood cells containing granules that stain with basic dyes, and which are thought to have a function similar to mast cells.


Bb is the large active fragment of complement component factor B. It is produced when factor B is captured by bound C3b and cleaved by factor D. Bb remains associated with C3b and is the serine protease component of the alternative pathway C3 convertase.

B-cell antigen receptor

The B-cell antigen receptor, or B-cell receptor (BCR), is the cell-surface receptor of B cells for specific antigen. It is composed of a transmembrane immunoglobulin molecule associated with the invariant Igα and Igβ chains in a noncovalent complex.

B-cell co-receptor

A complex of CD19, TAPA-1, and CR2 makes up the B-cell co-receptor; co-ligation of this complex with the B-cell antigen receptor increases responsiveness to antigen by about 100-fold.

B-cell corona

The B-cell corona in the spleen is the zone of the white pulp primarily made up of B cells.

B-cell mitogens

B-cell mitogens are substances that cause B cells to proliferate.


The protein known as Bcl-2 protects cells from apoptosis by binding to the mitochondrial membrane. It is encoded by the bcl-2 gene, which was discovered at the breakpoint of an oncogenic chromosomal translocation in B-cell leukemia.


see tyrosine kinase.


The adaptor protein BLNK operates in B cells in the same way as LAT does in T cells; it has multiple tyrosine residues that are targets for phosphorylation, and recruits signaling molecules to membrane lipid rafts.

Blood group antigens

Blood group antigens are surface molecules on red blood cells that are detectable with antibodies from other individuals. The major blood group antigens are called ABO and Rh (Rhesus), and are used in routine blood banking to type blood. There are many other blood group antigens that can be detected in cross-matching.

blood typing

In transfusion medicine, blood typing is used to determine whether donor and recipient have the same ABO and Rh blood group antigens. A cross-match, in which serum from the donor is tested on the cells of the recipient, and vice versa, is used to rule out other incompatibilities. Transfusion of incompatible blood causes a transfusion reaction, in which red blood cells are destroyed and the released hemoglobin causes toxicity.

Bloom’s syndrome

Bloom’s syndrome is a disease characterized by low T-cell numbers, reduced antibody levels, and an increased susceptibility to respiratory infections, cancer, and radiation damage. It is caused by mutations in a DNA helicase.

B lymphocyte

see B cell.

B-lymphocyte chemokine

B-lymphocyte chemokine (BLC) is a CXC chemokine that attracts B cells and activated T cells into the follicles of peripheral lymphoid tissues by binding to the CXCR5 receptor.


BLyS is a secreted member of the TNF family of cytokines. It is secreted by T cells and plays critical roles in germinal center and plasma-cell formation, and possibly dendritic-cell maturation.

bone marrow

The bone marrow is the site of hematopoiesis, the generation of the cellular elements of blood, including red blood cells, monocytes, polymorphonuclear leukocytes, and platelets. The bone marrow is also the site of B-cell development in mammals and the source of stem cells that give rise to T cells upon migration to the thymus. Thus, bone marrow transplantation can restore all the cellular elements of the blood, including the cells required for adaptive immunity.

bone marrow chimera

A bone marrow chimera is formed by transferring bone marrow from one mouse to an irradiated recipient mouse, so that all of the lymphocytes and blood cells are of donor genetic origin. Bone marrow chimeras have been crucial in elucidating the development of lymphocytes and other blood cells.

booster immunization

A booster immunization is commonly given after a primary immunization, to increase the titer of antibodies.


Bradykinin is a vasoactive peptide that is produced as a result of tissue damage and acts as an inflammatory mediator.

bronchial-associated lymphoid tissues

The lymphoid cells and organized lymphoid tissues in the respiratory tract have been termed the bronchial-associated lymphoid tissues (BALT). These tissues are very important in the induction of immune responses to inhaled antigens and to respiratory infection.

Bruton’s X-linked agammaglobulinemia

see X-linked agammaglobulinemia.

Burkitt’s lymphoma

Burkitt’s lymphoma is caused by Epstein–Barr virus (EBV) and occurs mainly in sub-Saharan Africa.

bursa of Fabricius

The bursa of Fabricius is an outpouching of the cloaca found in birds. It is an aggregate of epithelial tissue and lymphoid cells and is the site of intense early B-cell proliferation. The bursa of Fabricius is required for B-cell development in birds, as its removal or bursectomy early in life causes an absence of B cells in adult birds. An equivalent structure has not been detected in mammals, where B-cell development follows a different pathway.


C domains

The constant regions of the polypeptide chains of immunoglobulin molecules are made up of one or more constant domains or C domains of similar structure; each immunoglobulin chain also has a single variable or V domain.

C region

see constant region.

C1 complex

The C1 complex of complement components comprises one molecule of C1q bound to two molecules each of the zymogens C1r and C1s. C1q initiates the classical pathway of complement activation by binding to a pathogen surface or to bound antibody. This binding activates the associated C1r, which in turn cleaves and activates C1s. The active form of C1s then cleaves the next two components in the pathway, C4 and C2.

C1 inhibitor

C1 inhibitor (C1INH) is a protein that inhibits the activity of activated complement component C1 by binding to and inactivating its C1r:C1s enzymatic activity. It also inhibits other serine proteases including kallikrein. Deficiency in C1INH is the cause of the disease hereditary angioneurotic edema, in which the production of vasoactive peptides, kinins, leads to subcutaneous and laryngeal swelling.


The complement fragment C3b is the major product of the C3 convertase, and the principal effector molecule of the complement system. It has a highly reactive thioester bond which allows it to bind covalently to the surface on which it is generated. Once bound, it acts as an opsonin to promote the destruction of pathogens by phagocytes and removal of immune complexes; C3b is bound by the complement receptor CR1, while its proteolytic derivative, iC3b, is bound by the complement receptors CR1, CR2, and CR3.

C3 convertase

The generation of the enzyme C3 convertase on the surface of a pathogen or cell is a crucial step in complement activation. The classical pathway C3 convertase is formed from membrane-bound C4b complexed with the protease C2b. The alternative pathway of complement activation uses a different but homologous C3 convertase, formed from membrane-bound C3b complexed with the protease Bb. These C3 convertases have the same activity, catalyzing the deposition of large numbers of C3b molecules that bind covalently to the pathogen surface, leading to opsonization and the activation of the effector cascade that causes membrane lesions.


C3dg is a breakdown product of C3b that remains attached to the microbial surface, where it can bind to CD21, the complement receptor CR2.

C4b-binding protein

C4b-binding protein can inactivate the classical pathway C3 convertase if it forms on host cells, by displacing C2b from the C4b:C2b complex. It binds to C4b attached to host cells, but cannot bind C4b attached to pathogens. This is because it has a second binding site specific for sialic acid, a terminal sugar on vertebrate cell surfaces, but not on pathogens.


C5 is an inactive complement component that is cleaved by the C5 convertase to release the potent inflammatory peptide C5a and a larger fragment, C5b, that initiates the formation of a membraneattack complex from the terminal components of complement.

C5a receptor

The receptor for the C5a fragment of complement, the C5a receptor, is a seven-transmembrane spanning receptor that couples to a heterotrimeric G protein. Similar receptors bind to C3a and C4a.

C6, C7

The complement components C6, C7, and C8 form a complex with the active complement fragment C5b in the late events of complement activation. This complex inserts into the membrane and induces polymerization of C9 to form a pore known as the membrane-attack complex.


The cytosolic serine/threonine phosphatase calcineurin has a crucial role in signaling via the T-cell receptor. The immunosuppressive drugs cyclosporin A and tacrolimus (also known as FK506) form complexes with cellular proteins called immunophilins that bind and inactivate calcineurin, suppressing T-cell responses.


The protein calnexin is an 88 kDa protein found in the endoplasmic reticulum. It binds to partly folded members of the immunoglobulin superfamily of proteins and retains them in the endoplasmic reticulum until folding is completed.


Calreticulin is the molecular chaperone that binds initially to MHC class I, MHC class II, and other proteins that contain immunoglobulin-like domains, such as the T-cell and B-cell antigen receptors.


Antibodies or antigens can be measured in various capture assays. In these assays, antigens are captured by antibodies bound to plastic (or vice versa). Antibody binding to a plate-bound antigen can be measured using labeled antigen or anti-immunoglobulin. Antigen binding to plate-bound antibody can be measured by using an antibody that binds to a different epitope on the antigen.


Carriers are foreign proteins to which small nonimmunogenic antigens, or haptens, can be coupled to render the hapten immunogenic. In vivo, self proteins can also serve as carriers if they are correctly modified by the hapten; this is important in allergy to drugs.

Caseation necrosis

Caseation necrosis is a form of necrosis seen in the center of large granulomas, such as the granulomas in tuberculosis. The term comes from the white cheesy appearance of the central necrotic area.


Caspases are a family of closely related cysteine proteases that cleave proteins at aspartic acid residues. They have important roles in apoptosis.


see clusters of differentiation and Appendix II.

CD3 complex

The CD3 complex is the complex of α:β or γ:δ T-cell receptor chains with the invariant subunits CD3γ, δ, and ε, and the dimeric ζ chains.


The cell-surface protein CD4 is important for recognition by the T-cell receptor of antigenic peptides bound to MHC class II molecules. It acts as a co-receptor by binding to the lateral face of the MHC class II molecules.

CD4 T cells

CD4 T cells are T cells that carry the co-receptor protein CD4. They recognize peptides derived from intravesicular sources, which are bound to MHC class II molecules, and differentiate into CD4 TH1 and CD4 TH2 effector cells that activate macrophages and B-cell responses to antigen.

CD5 B cells

CD5 B cells are a class of atypical, self-renewing B cells found mainly in the peritoneal and pleural cavities in adults. They have a far less diverse receptor repertoire than conventional B cells, and since they are the first B cells to be produced they are also known as B-1 cells.


The cell-surface protein CD8 is important for recognition by the T-cell receptor of antigenic peptides bound to MHC class I molecules. It acts as a co-receptor by binding to the lateral face of MHC class I molecules.

CD8 T cells

CD8 T cells are T cells that carry the co-receptor CD8. They recognize antigens, for example viral antigens, that are synthesized in the cytoplasm of a cell. Peptides derived from these antigens are transported by TAP, assembled with MHC class I molecules in the endoplasmic reticulum, and displayed as peptide:MHC class I complexes on the cell surface. CD8 T cells differentiate into cytotoxic CD8 T cells.

CD19:CR2:TAPA-1 complex

see B-cell co-receptor.


see Appendix II.


see Appendix II.

CD30 and CD30L

see Appendix II.


see Appendix II.

CD40 ligand

B-cell growth is triggered in part by the binding of CD40 ligand, also known as CD154, expressed on activated helper T cells, to CD40 on the B-cell surface.


CD45, or the leukocyte common antigen, is a transmembrane tyrosine phosphatase found on all leukocytes. It is expressed in different isoforms on different cell types, including the different subtypes of T cells. These isoforms are commonly denoted by the designation of CD45R followed by the exon whose presence gives rise to distinctive antibody-binding patterns.


see protectin.


see complementarity determining region.

Cell-adhesion molecules

Cell-adhesion molecules (CAMs) are cell-surface proteins that are involved in binding cells together in tissues and also in less permanent cell–cell interactions.

Cell-mediated immunity

Cell-mediated immunity, or a cell-mediated immune response, describes any adaptive immune response in which antigen-specific T cells have the main role. It is defined operationally as all adaptive immunity that cannot be transferred to a naive recipient with serum antibody. Cf. humoral immunity.

Cell-surface immunoglobulin

Cell-surface immunoglobulin is the B-cell receptor for antigen. See also B-cell antigen receptor.

Cellular immunology

Cellular immunology is the study of the cellular basis of immunity.

Central lymphoid organs

Central lymphoid organs are sites of lymphocyte development. In humans, B lymphocytes develop in bone marrow, whereas T lymphocytes develop within the thymus from bone marrow-derived progenitors. They are also sometimes known as the primary lymphoid organs.

Central tolerance

Central tolerance is tolerance that is established in lymphocytes developing in central lymphoid organs. Cf. peripheral tolerance.


Centroblasts are large, rapidly dividing cells found in germinal centers, and are the cells in which somatic hypermutation is believed to occur. Antibody-secreting and memory B cells derive from these cells.


Centrocytes are the small B cells in germinal centers that derive from centroblasts. They may mature into antibody-secreting plasma cells or memory B cells, or may undergo apoptosis, depending on their receptor’s interaction with antigen.


Chediak–Higashi syndrome is caused by a defect in a protein involved in intracellular vesicle fusion. Phagocytic cell function is affected as lysosomes fail to fuse properly with phagosomes and there is impaired killing of ingested bacteria.


Chemokines are small chemoattractant proteins that stimulate the migration and activation of cells, especially phagocytic cells and lymphocytes. They have a central role in inflammatory responses. Chemokines and their receptors are listed in Appendix IV.

chromosomal translocations

Most lymphoid tumors, and many other tumors, bear chromosomal translocations that mark points of breakage and rejoining of different chromosomes. These chromosomal breaks are particularly frequent in lymphomas and leukemias.

Chronic granulomatous disease

Chronic granulomatous disease is an immunodeficiency disease in which multiple granulomas form as a result of defective elimination of bacteria by phagocytic cells. It is caused by defects in the NADPH oxidase system of enzymes that generate the superoxide radical involved in bacterial killing.

Chronic lymphocytic leukemias

Chronic lymphocytic leukemias (CLLs) are B-cell tumors that are found in the blood. The great majority express CD5 and unmutated V genes and are therefore thought to arise from B-1 cells.


The cell-surface receptor called c-Kit is found on many immature hematopoietic cells. It is a receptor for CSF.

class II-associated invariant chain peptide

The class II-associated invariant chain peptide (CLIP) is a peptide of variable length cleaved from the class II invariant chain by proteases. It remains associated with the MHC class II molecule in an unstable form until it is removed by the HLA-DM protein.

Class II transactivator

Class II transactivator (CIITA): see MHC class II transactivator.

Class switching

see isotype switching.


see isotypes.

classical pathway

The classical pathway of complement activation is the pathway activated by C1 binding either directly to bacterial surfaces or to antibody, that serves as a means of flagging the bacteria as foreign. See also alternative pathway; mannan-binding lectin.

Clonal deletion

Clonal deletion is the elimination of immature lymphocytes on binding to self antigens to produce tolerance to self, as required by the clonal selection theory. Clonal deletion is the main mechanism of central tolerance and can also occur in peripheral tolerance.

Clonal expansion

Clonal expansion is the proliferation of antigen-specific lymphocytes in response to antigenic stimulation and precedes their differentiation into effector cells. It is an essential step in adaptive immunity, allowing rare antigen-specific cells to increase in number so that they can effectively combat the pathogen that elicited the response.

clonal selection theory

The clonal selection theory is a central paradigm of adaptive immunity. It states that adaptive immune responses derive from individual antigen-specific lymphocytes that are self-tolerant. These specific lymphocytes proliferate in response to antigen and differentiate into antigen-specific effector cells that eliminate the eliciting pathogen, and memory cells to sustain immunity. The theory was formulated by Sir Macfarlane Burnet and in earlier forms by Niels Jerne and David Talmage.


A clone is a population of cells all derived from a single progenitor cell.

cloned T-cell line

A cloned T-cell line is a continuously growing line of T cells derived from a single progenitor cell. Cloned T-cell lines must be stimulated with antigen periodically to maintain growth. They are useful for studying T-cell specificity, growth, and effector functions.


A feature unique to individual cells or members of a clone is said to be clonotypic. Thus, a monoclonal antibody that reacts with the receptor on a cloned T-cell line is said to be a clonotypic antibody and to recognize its clonotype or the clonotypic receptor of that cell. See also idiotype; idiotypic.

Clusters of differentiation

Clusters of differentiation (CD) are groups of monoclonal antibodies that identify the same cell-surface molecule. The cell-surface molecule is designated CD followed by a number (e.g. CD1, CD2, etc.). For a current listing of CDs see Appendix II.

coagulation system

The coagulation system is a proteolytic cascade of plasma enzymes that triggers blood clotting when blood vessels are damaged.


The expression of a gene is said to be codominant when both alleles at one locus are expressed in roughly equal amounts in heterozygotes. Most genes show this property, including the highly polymorphic MHC genes.

coding joint

A coding joint is formed by the imprecise joining of a V gene segment to a (D)J gene segment in immunoglobulin or T-cell receptor genes.


see immunoprecipitation analysis.


see congenic.


Collectins are a structurally related family of calcium-dependent sugar-binding proteins or lectins containing collagen-like sequences. An example is mannan-binding lectin.

combinatorial diversity

Antigen receptors manifest two distinct types of combinatorial diversity generated by the combination of separate units of genetic information. Receptor gene segments are joined in many different combinations to generate diverse receptor chains, and then two different receptor chains (heavy and light in immunoglobulins; α and β or γ and δ in T-cell receptors) are combined to make the antigen-recognition site.

common γ chain

The common γ chain (γc) is a transmembrane polypeptide chain (CD132) that is common to a subgroup of class I cytokine receptors. It plays a key role in the intracellular signaling mediated by these receptors as shown by gene knockout.

Common lymphoid progenitors

Common lymphoid progenitors are stem cells that give rise to all lymphocytes. They are derived from pluripotent hematopoietic stem cells.

Common variable immunodeficiency

Common variable immunodeficiency is a relatively common deficiency in antibody production whose pathogenesis is not yet understood. There is a strong association with genes mapping within the MHC.

Competitive binding assays

Competitive binding assays are serological assays in which unknowns are detected and quantitated by their ability to inhibit the binding of a labeled known ligand to its specific antibody. This is also referred to as a competitive inhibition assay.

competitive inhibition assay

When known sources of antibody or antigen are used as competitive inhibitors of antigen–antibody interactions, this assay is referred to as a competitive inhibition assay.


The complement system is a set of plasma proteins that act together to attack extracellular forms of pathogens. Complement activation can occur spontaneously on certain pathogens or by antibody binding to the pathogen. The pathogen becomes coated with complement proteins that facilitate pathogen removal by phagocytes and can also kill certain pathogens directly.

Complement receptors

Complement receptors (CRs) are cell-surface proteins on various cells that recognize and bind complement proteins that have bound an antigen such as a pathogen. Complement receptors on phagocytes allow them to identify pathogens coated with complement proteins for uptake and destruction. Complement receptors include CR1, CR2, CR3, CR4, and the receptor for C1q.

complementarity determining regions

The complementarity determining regions (CDRs) of immuno-globulins and T-cell receptors are the parts of these molecules that determine their specificity and make contact with specific ligand. The CDRs are the most variable part of the molecule, and contribute to the diversity of these molecules. There are three such regions (CDR1, CDR2, and CDR3) in each V domain.

confocal fluorescent microscopy

In confocal fluorescent microscopy, it is possible to use optics to produce images at very high resolution by having two origins of fluorescent light that come together only at one plane of a thicker section.

Conformational epitopes

Conformational epitopes, or discontinuous epitopes, on a protein antigen are formed from several separate regions in the primary sequence of a protein brought together by protein folding. Antibodies that bind conformational epitopes bind only native folded proteins.


Congenic strains of mice are genetically identical at all loci except one. Each strain is generated by the repetitive back-crossing of mice carrying the desired trait onto a strain that provides the genetic background for the set of congenic strains. The most important congenic strains in immunology are the congenic strains, developed by George Snell, that differ from each other at the MHC.

Conjugate vaccines

Conjugate vaccines are vaccines made from capsular polysaccharides bound to proteins of known immunogenicity, such as tetanus toxoid.

constant region

The constant region (C region) of an immunoglobulin or T-cell receptor is that part of the molecule that is relatively constant in amino acid sequence between different molecules. In an antibody molecule the constant regions of each chain are composed of one or more C domains. The constant region of an antibody determines its particular effector function. Cf. variable region.

contact hypersensitivity reaction

A contact hypersensitivity reaction is a form of delayed-type hypersensitivity in which T cells respond to antigens that are introduced by contact with the skin. Poison ivy hypersensitivity is a contact hypersensitivity reaction due to T-cell responses to the chemical antigen pentadecacatechol in poison ivy leaves.

Continuous epitopes

Continuous epitopes, or linear epitopes, are antigenic determinants on proteins that are contiguous in the amino acid sequence and therefore do not require the protein to be folded into its native conformation for antibody to bind. The epitopes detected by T cells are continuous.


A convertase is an enzymatic activity that converts a complement protein into its reactive form by cleaving it. Generation of the C3 convertase is the pivotal event in complement activation.

Coombs test

The Coombs test is a test for antibody binding to red blood cells. Red blood cells that are coated with antibody are agglutinated if they are exposed to an anti-immunoglobulin antibody. The Coombs test is important in detecting the nonagglutinating antibodies against red blood cells produced by Rh incompatibility in pregnancy.


Two binding sites are said to demonstrate cooperativity in binding to their ligand when the binding of ligand to one site enhances the binding of ligand to the second site.


A co-receptor is a cell-surface protein that increases the sensitivity of the antigen receptor to antigen by binding to associated ligands and participating in signaling for activation. CD4 and CD8 are MHC-binding co-receptors on T cells, whereas CD19 is part of a complex that makes up a co-receptor on B cells.


see B-cell corona.


Corticosteroids are a family of drugs related to steroids that are naturally produced in the adrenal cortex, such as cortisone. Corticosteroids can kill lymphocytes, especially developing thymocytes, inducing apoptotic cell death. They are useful anti-inflammatory, anti-lymphoid tumor, and immunosuppressive agents.

co-stimulatory signal

The proliferation of lymphocytes requires both antigen binding and the receipt of a co-stimulatory signal. Co-stimulatory signals are delivered to T cells by the co-stimulatory molecules, B7.1 and B7.2, related molecules that are expressed on the surface of the cell presenting antigen, and which bind the T-cell surface molecule CD28. B cells may receive co-stimulatory signals from common pathogen components such as LPS, from complement fragments, or from CD40 ligand expressed on the surface of an activated antigenspecific helper T cell.


Cowpox is the common name of the disease produced by vaccinia virus, used by Edward Jenner in the successful vaccination against smallpox, which is caused by the related variola virus.


see complement receptors.


CR1 (CD35) is one of several receptors on cells for various components of complement. It is used to remove immune complexes from the plasma.


CR2 (CD21) is part of the B-cell co-receptor complex along with CD19 and CD81. It binds to antigens that have various breakdown products of C3, especially C3d, bound to them and, by cross-linking to the B-cell receptor, enhances sensitivity to antigen by at least a hundredfold. It is also used by the Epstein–Barr virus to invade B cells and produce the symptoms of infectious mononucleosis.


CR3 (CD11b:CD18) is a β2 integrin that functions both as an adhesion molecule and as a complement receptor. It binds iC3b, and stimulates phagocytosis.


CR4 (CD11c:CD18) is a β2 integrin that binds iC3b and stimulates phagocytosis.

C-reactive protein

C-reactive protein is an acute-phase protein that binds to phosphorylcholine, which is a constituent of the C-polysaccharide of the bacterium Streptococcus pneumoniae, hence its name. Many other bacteria also have surface phosphorylcholine that is accessible to C-reactive protein, so the protein can bind many different bacteria and opsonize them for uptake by phagocytes. C-reactive protein does not bind to mammalian tissues.


Cross-matching is used in blood typing and histocompatibility testing to determine whether donor and recipient have antibodies against each other’s cells that might interfere with successful transfusion or grafting.


A cross-reaction is the binding of antibody to an antigen not used to elicit that antibody. Thus, if antibody raised against antigen A also binds antigen B, it is said to cross-react with antigen B. The term is used generically to describe the reactivity of antibodies or T cells with antigens other than the eliciting antigen.


The protein known as Csk or C-terminal Src kinase is constitutively active in lymphocytes and has the function of phosphorylating the C-terminal tyrosine of Src-family tyrosine kinases, thus inactivating them.


CTLA-4 is the high-affinity receptor for B7 molecules on T cells.

Cutaneous lymphocyte antigen

Cutaneous lymphocyte antigen (CLA) is a cell-surface molecule that is involved in lymphocyte homing to the skin in humans.

Cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma is a malignant growth of T cells that home to the skin.


Cyclophosphamide is a DNA alkylating agent that is used as an immunosuppressive drug. It acts by killing rapidly dividing cells, including lymphocytes proliferating in response to antigen.

Cyclosporin A

Cyclosporin A is a powerful immunosuppressive drug that inhibits signaling from the T-cell receptor, preventing T-cell activation and effector function. It binds to cyclophilin, and this complex binds to and inactivates the serine/threonine phosphatase calcineurin.

Cytokine capture

see antigen capture.

Cytokine receptors

Cytokine receptors are cellular receptors for cytokines. Binding of the cytokine to the cytokine receptor induces new activities in the cell, such as growth, differentiation, or death. Cytokine receptors are listed in Appendix III.


Cytokines are proteins made by cells that affect the behavior of other cells. Cytokines made by lymphocytes are often called lymphokines or interleukins (abbreviated IL), but the generic term cytokine is used in this book and most of the literature. Cytokines act on specific cytokine receptors on the cells that they affect. Cytokines and their receptors are listed in Appendix III. See also chemokines.

cytotoxic T cells

T cells that can kill other cells are called cytotoxic T cells. Most cytotoxic T cells are MHC class I-restricted CD8 T cells, but CD4 T cells can also kill in some cases. Cytotoxic T cells are important in host defense against cytosolic pathogens.


Cytotoxins are proteins made by cytotoxic T cells that participate in the destruction of target cells. Perforins and granzymes are the major defined cytotoxins.


In the context of immunoglobulins, δ is the type of heavy chain in IgD.

D gene segments

D gene segments, or diversity gene segments, are short DNA sequences that join the V and J gene segments in rearranged immunoglobulin heavy-chain genes and in T-cell receptor β and δ chain genes. See gene segments.

Dark zone

see germinal centers.

Death domains

Death domains were originally defined in proteins encoded by genes involved in programmed cell death or apoptosis, and are now known to be involved in protein–protein interactions.

decay-accelerating factor

The decay-accelerating factor (DAF or CD55) is a cell-surface molecule that protects cells from lysis by complement. Its absence causes the disease paroxysmal nocturnal hemoglobinuria.

Defective endogenous retroviruses

Defective endogenous retroviruses are partial retroviral genomes integrated into host cell DNA and carried as host genes. There are a great many defective endogenous retroviruses in the mouse genome.

Delayed-type hypersensitivity

Delayed-type hypersensitivity, or type IV hypersensitivity, is a form of cell-mediated immunity elicited by antigen in the skin and is mediated by CD4 TH1 cells. It is called delayed-type hypersensitivity because the reaction appears hours to days after antigen is injected. Cf. immediate hypersensitivity.

Dendritic cells

Dendritic cells, also known as interdigitating reticular cells, are found in T-cell areas of lymphoid tissues. They have a branched or dendritic morphology and are the most potent stimulators of T-cell responses. Nonlymphoid tissues also contain dendritic cells, but these are not able to stimulate T-cell responses until they are activated and migrate to lymphoid tissues. The dendritic cell derives from bone marrow precursors. It is distinct from the follicular dendritic cell that presents antigen to B cells.

Dendritic epidermal T cells

Dendritic epidermal T cells (dETCs), are a specialized class of γ:δ T cells found in the skin of mice and some other species, but not humans. All dETCs have the same γ:δ T-cell receptor; their function is unknown.


Desensitization is a procedure in which an allergic individual is exposed to increasing doses of allergen in hopes of inhibiting their allergic reactions. It probably involves shifting the balance between CD4 TH1 and TH2 cells and thus changing the antibody produced from IgE to IgG.

Determinant spreading

see epitope spreading.


Diacylglycerol (DAG) is most commonly released from inositol phospholipids by the action of phospholipase C-γ. Diacylglycerol production is stimulated by the ligation of many receptors and it acts as an intracellular signaling molecule, activating cytosolic protein kinase C, which further propagates the signal.


Diapedesis is the movement of blood cells, particularly leukocytes, from the blood across blood vessel walls into tissues.

differential signaling hypothesis

The differential signaling hypothesis proposes that qualitatively different antigens might mediate the positive and negative selection of T cells in the thymus. Cf. avidity hypothesis.

Differentiation antigens

Differentiation antigens are proteins detected on some cells by means of specific antibodies. Many differentiation antigens have important functional roles characteristic of the differentiated phenotypes of the cell on which they are expressed, such as cell-surface immunoglobulin on B cells.

DiGeorge’s syndrome

DiGeorge’s syndrome is a recessive genetic immunodeficiency disease in which there is a failure to develop thymic epithelium, and is associated with absent parathyroid glands and large vessel anomalies. It seems to be due to a developmental defect in neural crest cells.

direct Coombs test

The direct Coombs test uses anti-immunoglobulin to agglutinate red blood cells as a way of detecting whether they are coated with antibody in vivo due to autoimmunity or maternal anti-fetal immune responses (see Coombs test; indirect Coombs test).

Discontinuous epitopes

see conformational epitopes.

DNA microarrays

DNA microarrays are created by placing a different DNA on a small part of a microchip, and using them to assess RNA expression in normal or malignant cells.

DNA vaccination

When vaccinating with plasmid DNA, it was seen that an adaptive immune response to the encoded protein occurred, leading to the term DNA vaccination. This lead to the realization that bacterial DNA, which is loaded with unmethylated CpG dinucleotides, was adjuvant for this type of vaccination.

DNA-dependent kinase

The genetic defect in scid mice, which cannot rearrange their T- or B-cell receptor genes and have a severe combined immunodeficiency phenotype, is in the enzyme DNA-dependent kinase. This enzyme is part of a complex of proteins that bind to the hairpin ends of double-stranded breaks in DNA, and its catalytic subunit is critical for VDJ recombination.


In tissue grafting experiments, the grafted tissues come from a donor and are placed in a recipient or host.

Double-negative thymocytes

Double-negative thymocytes are immature T cells within the thymus that lack expression of the two co-receptors, CD4 and CD8. In a normal thymus, these represent about 5% of thymocytes.

Double-positive thymocytes

Double-positive thymocytes are an intermediate stage in T-cell development in the thymus and are characterized by expression of both the CD4 and the CD8 co-receptor proteins. They represent the majority (~80%) of thymocytes.

draining lymph node

The term draining lymph node is used for any lymph node that is downstream of a site of infection and thus receives antigens and microbes from the site via the lymphatic system. Draining lymph nodes often enlarge enormously during an immune response and can be palpated; they were originally called swollen glands.


In the context of immunoglobulins, ε (epsilon) is the heavy chain of IgE.

early induced responses

The early induced responses or early nonadaptive responses are a series of host defense responses that are triggered by infectious agents early in infection. They are distinct from innate immunity because there is an inductive phase, and from adaptive immunity in that they do not operate by clonal selection of rare antigen-specific lymphocytes.

Early pro-B cell

see pro-B cell.


The common skin disease eczema is seen mainly in children; its etiology is poorly understood.


In immunology, edema is the swelling caused by the entry of fluid and cells from the blood into the tissues, which is one of the cardinal features of the process of inflammation.

Effector lymphocytes

Effector lymphocytes can mediate the removal of pathogens from the body without the need for further differentiation, as distinct from naive lymphocytes, which must proliferate and differentiate before they can mediate effector functions, and memory cells, which must differentiate and often proliferate before they become effector cells. They are also called armed effector cells in this book, to indicate that they can be triggered to effector function by antigen binding alone.

Effector mechanisms

Effector mechanisms are those processes by which pathogens are destroyed and cleared from the body. Innate and adaptive immune responses use most of the same effector mechanisms to eliminate pathogens.

efferent lymphatic vessel

Lymphocytes leave a lymph node through the efferent lymphatic vessel.


Electrophoresis is the movement of molecules in a charged field. In immunology, many forms of electrophoresis are used to separate molecules, especially protein molecules, to determine their charge, size, and subunit composition.


see enzyme-linked immunosorbent assay.


ELISPOT assay is an adaptation of ELISA in which cells are placed over antibodies or antigens attached to a plastic surface. The antigen or antibody traps the cells’ secreted products, which can then be detected using an enzyme-coupled antibody that cleaves a colorless substrate to make a localized colored spot.

Embryonic stem

Embryonic stem (ES) cells are mouse embryonic cells that will grow continuously in culture and that retain the ability to contribute to all cell lineages. ES cells can be genetically manipulated in tissue culture and then inserted into mouse blastocysts to generate mutant lines of mice; most often, genes are deleted in ES cells by homologous recombination and the mutant ES cells are then used to generate gene knockout mice. They have also been used to clone sheep, and could soon be used to replace body parts in humans.

Encapsulated bacteria

Encapsulated bacteria have thick carbohydrate coats that protect them from phagocytosis. Encapsulated bacteria can cause extracellular infections and are effectively engulfed and destroyed by phagocytes only if they are first coated with antibody and complement produced in an adaptive immune response.

endogenous pyrogens

Cytokines that can induce a rise in body temperature are called endogenous pyrogens, as distinct from exogenous substances such as endotoxin from gram-negative bacteria that induce fever by triggering endogenous pyrogen synthesis and release.


Antigen taken up by phagocytosis generally enters the endosomes, the acidified vesicles present in cells. Protein antigens entering by this route are presented by MHC class II molecules.


Endotoxins are bacterial toxins that are released only when the bacterial cell is damaged, as opposed to exotoxins, which are secreted bacterial toxins. The most important endotoxin is the lipopolysaccharide of gram-negative bacteria, which is a potent inducer of cytokine synthesis and the proximal cause of endotoxic shock.


Within genomic DNA, there are specific sequences that act as cell-specific enhancers of RNA transcription.

enzyme-linked immunosorbent assay

The enzyme-linked immunosorbent assay (ELISA) is a serological assay in which bound antigen or antibody is detected by a linked enzyme that converts a colorless substrate into a colored product. The ELISA assay is widely used in biology and medicine as well as in immunology.


Eosinophils are white blood cells thought to be important chiefly in defense against parasitic infections; they are activated by the lymphocytes of the adaptive immune response. The level of eosinophils in the blood is normally quite low. It can increase markedly in several situations, such as atopy, resulting in eosinophilia, an abnormally large number of eosinophils in the blood.


Eotaxin-1 and eotaxin-2 are CC chemokines that act specifically on eosinophils.


An epitope is a site on an antigen recognized by an antibody or an antigen receptor; epitopes are also called antigenic determinants. A T-cell epitope is a short peptide derived from a protein antigen. It binds to an MHC molecule and is recognized by a particular T cell. B-cell epitopes are antigenic determinants recognized by B cells and are typically discontinuous in the primary structure.

Epitope spreading

Epitope spreading describes the fact that responses to autoantigens tend to become more diverse as the response persists. This is also called determinant spreading or antigen spreading.

Epstein–Barr virus

The Epstein–Barr virus (EBV) is a herpesvirus that selectively infects human B cells by binding to complement receptor 2 (CR2, also known as CD21). It causes infectious mononucleosis and establishes a lifelong latent infection in B cells that is controlled by T cells. Some B cells latently infected with EBV will proliferate in vitro to form lymphoblastoid cell lines.

equilibrium dialysis

The affinity of an antibody for its antigen can be determined by equilibrium dialysis, a technique in which antibody in a dialysis bag is exposed to varying amounts of a small antigen able to diffuse across the dialysis membrane. The amount of antigen inside and outside the bag at the equilibrium diffusion state is determined by the amount and affinity of the antibody in the bag.


E-rosettes are human T cells that will bind to treated red blood cells from sheep; the many red blood cells bound to each T cell give it the appearance of a rosette and increase its buoyant density so that the T cells can be isolated by gradient centrifugation. E-rosetting is often used for isolating human T cells.


Erp57 is a chaperone molecule involved in loading peptide onto MHC class I molecules in the endoplasmic reticulum.

Erythroblastosis fetalis

Erythroblastosis fetalis is a severe form of Rh hemolytic disease in which maternal anti-Rh antibody enters the fetus and produces a hemolytic anemia so severe that the fetus has mainly immature erythroblasts in the peripheral blood.


see selectins.

Experimental allergic encephalomyelitis

Experimental allergic encephalomyelitis (EAE) is an inflammatory disease of the central nervous system that develops after mice are immunized with neural antigens in a strong adjuvant.


The movement of cells or fluid from within blood vessels to the surrounding tissues is called extravasation.


Fab fragments

IgG antibody molecules can be cleaved into three fragments by the enzyme papain. Two of these are identical Fab fragments, so called because they are the Fragment with specific antigen binding. The Fab fragment consists of the light chain and the N-terminal half of the heavy chain held together by an interchain disulfide bond. Another protease, pepsin, cuts in the same general region of the antibody molecule as papain but on the carboxy-terminal side of the disulfide bonds. This produces the F(ab′)2 fragment, in which the two arms of the antibody molecule remain linked. See also Fc fragment.


see fluorescence-activated cell sorter.

Factor B, factor D, factor H, factor I,

Factor B, factor D, factor H, factor I, and factor P are all components of the alternative pathway of complement activation. Factor B plays a role very similar to that of C2b in the classical pathway. Factor D is a serine protease that cleaves factor B. Factor H is an inhibitory protein with a role similar to decay-accelerating factor. Factor I is a protease that breaks down various components of the alternative pathway. Factor P, or properdin, is a positive regulatory component of the alternative pathway. It stabilizes the C3 convertase of the alternative pathway on the surface of bacterial cells.

Farmer’s lung

Farmer’s lung is a hypersensitivity disease caused by the interaction of IgG antibodies with large amounts of an inhaled allergen in the alveolar wall of the lung, causing alveolar wall inflammation and compromising gas exchange.


Fas is a member of the TNF receptor family; it is expressed on certain cells and makes them susceptible to killing by cells expressing Fas ligand, a cell-surface member of the TNF family of proteins. Binding of Fas ligand to Fas triggers apoptosis in the Fas-bearing cell.

Fc fragment

IgG antibody molecules can be cleaved into three fragments by the enzyme papain. One of these is the Fc fragment, so-called for Fragment crystallizable. The Fc fragment consists of the C-terminal halves of the two heavy chains disulfide-bonded to each other by the residual hinge region. See also Fab fragments.

Fc receptors

Fc receptors are receptors for the Fc portion of immunoglobulin isotypes. They include the Fcγ and Fcε receptors.

Fcε receptor

The high-affinity Fcε receptor (FcεRI) on the surface of mast cells and basophils binds free IgE. When antigen binds this IgE and cross-links FcεRI, it causes mast-cell activation.

Fcγ receptors

Fcγ receptors, including FcγRI, RII, and RIII, are cell-surface receptors that bind the Fc portion of IgG molecules. Most Fcγ receptors bind only aggregated IgG, allowing them to discriminate bound antibody from free IgG. They are expressed on phagocytes, B lymphocytes, NK cells, and follicular dendritic cells. They have a key role in humoral immunity, linking antibody binding to effector cell functions.

first set rejection

When tissue or organ grafts are placed in an unmatched recipient, they are rejected by a first set rejection, which is an immune response by the host against foreign antigens in the graft. Cf. second set rejection.


see tacrolimus.

fluorescence-activated cell sorter

Individual cells can be characterized and separated in a machine called a fluorescence-activated cell sorterFACS® that measures cell size, granularity, and fluorescence due to bound fluorescent antibodies as single cells pass in a stream past photodetectors. The analysis of single cells in this way is called flow cytometry and the instruments that carry out the measurements and/or sort cells are called flow cytometers or cell sorters.


Peripheral lymphoid tissues, such as lymph nodes and Peyer’s patches, contain large areas of B cells called follicles, which are organized around follicular dendritic cells.

follicular center cell lymphoma

A follicular center cell lymphoma is a type of B-cell lymphoma that tends to grow in the follicles of lymphoid tissues.

follicular dendritic cells

The follicular dendritic cells of lymphoid follicles are cells of uncertain origin. They are characterized by long branching processes that make intimate contact with many different B cells. They have Fc receptors that are not internalized by receptor-mediated endocytosis and thus hold antigen:antibody complexes on the surface for long periods. These cells are crucial in selecting antigen-binding B cells during antibody responses.

framework regions

The V domains of immunoglobulins and T-cell receptors contain relatively invariant framework regions that provide a protein scaffold for the hypervariable regions that make contact with antigen.


Fungi are single-celled and multicellular eukaryotic organisms, including the yeasts and molds, that can cause a variety of diseases. Immunity to fungi is complex and involves both humoral and cellmediated responses.


see single-chain Fv.


see tyrosine kinase.


In the context of immunoglobulins, γ is the heavy chain of IgG.

G proteins

G proteins are intracellular proteins that bind GTP and convert it to GDP in the process of cell signal transduction. There are two kinds of G protein, the heterotrimeric (α, β, γ) receptor-associated G proteins, and the small G proteins, such as Ras and Raf, that act downstream of many transmembrane signaling events.


see gut-associated lymphoid tissues.

γ:δ T-cell receptor

Most T lymphocytes have α:β heterodimeric T-cell receptors, but some bear a distinct γ:δ T-cell receptor composed of different antigen-recognition chains, γ and δ, assembled in a γ:δ heterodimer. Cells bearing these receptors are called γ:δ T cells and their specificity and function are not yet clear.

γ globulins

Plasma proteins can be separated on the basis of electrophoretic mobility into albumin and the α, β, and γ globulins. Most antibodies migrate in electrophoresis as γ globulins (or gamma globulins), and patients who lack antibodies are said to have agammaglobulinemia.


see guanine-nucleotide exchange factor.

gene conversion

In birds and rabbits, immunoglobulin receptor diversity is generated mainly by gene conversion, in which homologous inactive V gene segments exchange short sequences with an active, rearranged V-region gene.

Gene knockout

Gene knockout is jargon for gene disruption by homologous recombination.

gene segments

The V domains of the polypeptide chains of antigen receptors are encoded in sets of gene segments that must first undergo somatic recombination to form a complete V-domain exon. There are three types of gene segment: V gene segments that encode the first 95 amino acids, D gene segments that encode about 5 amino acids, and J gene segments that form the last 10–15 amino acids of the V region. There are multiple copies of each type of gene segment in the germline DNA, but only one is expressed for each type of receptor chain in a receptor-bearing lymphocyte.

gene targeting

A gene can be specifically disrupted by a technique known as gene targeting or gene knockout. Usually this involves homologous recombination in embryonic stem cells followed by the preparation of chimeric mice by injection of these cells into the blastocyst.

Gene therapy

Gene therapy is the correction of a genetic defect by the introduction of a normal gene into bone marrow or other cell types. It is also known as somatic gene therapy because it does not affect the germline genes of the individual.

Genetic immunization

Genetic immunization is a novel technique for inducing adaptive immune responses. Plasmid DNA encoding a protein of interest is injected into muscle; for unknown reasons, it is expressed and elicits antibody and T-cell responses to the protein encoded by the DNA.


Mice that are raised in the complete absence of intestinal and other flora are called germ-free or gnotobiotic mice. Such mice have very depleted immune systems, but they can respond virtually normally to any specific antigen, provided it is mixed with a strong adjuvant.

Germinal centers

Germinal centers in secondary lymphoid tissues are sites of intense B-cell proliferation, selection, maturation, and death during antibody responses. Germinal centers form around follicular dendritic cell networks when activated B cells migrate into lymphoid follicles. They can be divided by morphology into the dark zone, which is rich in proliferating B lymphocytes, and a light zone, which contains FDCs and centrocytes.

germline configuration

Immunoglobulin and T-cell receptor genes are said to be in the germline configuration in the DNA of germ cells and in all somatic cells in which somatic recombination has not occurred.

germline diversity

The germline diversity of antigen receptors is due to the inheritance of multiple gene segments that encode V domains; such diversity is distinguished from the diversity that is generated during gene rearrangement or after receptor gene expression, which is somatically generated.

germline theory

One theory of antibody diversity, the germline theory, proposed that each antibody was encoded in a separate germline gene. This is now known not to happen in people, mice, and most other organisms, but appears to happen in Elasmobranchs, which have rearranged genes in the germline.


GlyCAM-1 is a mucinlike molecule found on the high endothelial venules of lymphoid tissues. It is an important ligand for the L-selectin molecule expressed on naive lymphocytes, directing these cells to leave the blood and enter the lymphoid tissues.


see germ-free.

Goodpasture’s syndrome

Goodpasture’s syndrome is an autoimmune disease in which autoantibodies against basement membrane or type IV collagen are produced and cause extensive vasculitis. It is rapidly fatal.

graft rejection

Tissue and organ grafts between genetically distinct individuals almost always elicit an adaptive immune response that causes graft rejection, the destruction of the grafted tissue by attacking lymphocytes.


When mature T lymphocytes are injected into a nonidentical immunoincompetent recipient, they can attack the recipient, causing a graft-versus-host (GVH) reaction; in human patients, mature T cells in allogeneic bone marrow grafts can cause graft-versus-host disease (GVHD).


see polymorphonuclear leukocyte.

Granulocyte-macrophage colony-stimulating factor

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine involved in the growth and differentiation of myeloid and monocytic lineage cells, including dendritic cells, monocytes and tissue macrophages, and cells of the granulocyte lineage.


A granuloma is a site of chronic inflammation usually triggered by persistent infectious agents such as mycobacteria or by a nondegradable foreign body. Granulomas have a central area of macrophages, often fused into multinucleate giant cells, surrounded by T lymphocytes.


Granzymes are serine proteases produced by cytotoxic T cells and are involved in inducing apoptosis in the target cell.

Graves’ disease

Graves’ disease is an autoimmune disease in which antibodies against the thyroid-stimulating hormone receptor cause overproduction of thyroid hormone and thus hyperthyroidism.

guanine-nucleotide exchange factors

The guanine-nucleotide exchange factors (GEFs) are proteins that can remove the bound GDP from small G proteins; this allows GTP to bind and activate the G protein.

gut-associated lymphoid tissues

The gut-associated lymphoid tissues (GALT) are lymphoid tissues closely associated with the gastrointestinal tract, including the palatine tonsils, Peyer’s patches, and intraepithelial lymphocytes. The GALT has a distinctive biology related to its exposure to antigens from food and normal intestinal microbial flora.


H antigens

H antigens or histocompatibility antigens, are known as major histocompatibility antigens when they encode molecules that present foreign peptides to T cells and as minor H antigens when they present polymorphic self peptides to T cells. See also histocompatibility.


The major histocompatibility complex of the mouse is called H-2 (for histocompatibility-2). Haplotypes are designated by a lower-case superscript, as in H-2b.


A haplotype is a linked set of genes associated with one haploid genome. The term is used mainly in connection with the linked genes of the major histocompatibility complex, which are usually inherited as one haplotype from each parent. Some MHC haplotypes are overrepresented in the population, a phenomenon known as linkage disequilibrium.


Haptens are molecules that can bind antibody but cannot by themselves elicit an adaptive immune response. Haptens must be chemically linked to protein carriers to elicit antibody and T-cell responses.

Hashimoto’s thyroiditis

Hashimoto’s thyroiditis is an autoimmune disease characterized by persistent high levels of antibody against thyroid-specific antigens. These antibodies recruit NK cells to the tissue, leading to damage and inflammation.

heavy chain

All immunoglobulin molecules have two types of chain, a heavy chain (H chain) of 50–70 kDa and a light chain of 25 kDa. The basic immunoglobulin unit consists of two identical heavy chains and two identical light chains. Heavy chains come in a variety of heavy-chain classes or isotypes, each of which confers a distinctive functional activity on the antibody molecule.

Helper CD4 T cells

Helper CD4 T cells are CD4 T cells that can help B cells make antibody in response to antigenic challenge. The most efficient helper T cells are also known as TH2 cells, which make the cytokines IL-4 and IL-5. Some experts refer to all CD4 T cells, regardless of function, as helper T cells; we do not accept this usage because function can be determined only in cellular assays, and some CD4 T cells kill the cells they interact with.


A hemagglutinin is any substance that causes red blood cells to agglutinate, a process known as hemagglutination. The hemagglutinins in human blood are antibodies that recognize the ABO blood group antigens. Influenza and some other viruses have hemagglutinin molecules that bind to glycoproteins on host cells to initiate the infectious process.


Hematopoiesis is the generation of the cellular elements of blood, including the red blood cells, leukocytes, and platelets. These cells all originate from pluripotent hematopoietic stem cells whose differentiated progeny divide under the influence of hematopoietic growth factors.

hematopoietic lineage

A hematopoietic lineage is any developmental series of cells that derives from hematopoietic stem cells and results in the production of mature blood cells.

Hemolytic disease of the newborn

see erythroblastosis fetalis.

Recombination signal sequences

Recombination signal sequences (RSS) flanking gene segments consist of a seven-nucleotide heptamer and a nine-nucleotide nonamer of conserved sequence, separated by 12 or 23 nucleotides. RSSs form the target for the site-specific RAG-1:RAG-2 recombinase that joins the gene segments.

Hereditary angioneurotic edema

Hereditary angioneurotic edema is the clinical name for a genetic deficiency of the C1 inhibitor of the complement system. In the absence of C1 inhibitor, spontaneous activation of the complement system can cause diffuse fluid leakage from blood vessels, the most serious consequence of which is epiglottal swelling leading to suffocation.


Individuals heterozygous for a particular gene have two different alleles of that gene.

Heymann’s nephritis

An excellent model for membranous glomerulonephritis is Heymann’s nephritis, a disease induced by injecting animals with tubular epithelial tissue.

High endothelial venules

High endothelial venules (HEVs) are specialized venules found in lymphoid tissues. Lymphocytes migrate from blood into lymphoid tissues by attaching to and migrating across the high endothelial cells of these vessels.

high-zone tolerance

Tolerance to injected protein antigens occurs at low or high doses of antigen. Tolerance induced by the injection of high doses of antigen is called high-zone tolerance, whereas tolerance produced with low doses of antigen is called low-zone tolerance.

hinge region

The hinge region of antibody molecules is a flexible domain that joins the Fab arms to the Fc piece. The flexibility of the hinge region in IgG and IgA molecules allows the Fab arms to adopt a wide range of angles, permitting binding to epitopes spaced variable distances apart.


Histamine is a vasoactive amine stored in mast cell granules. Histamine released by antigen binding to IgE molecules on mast cells causes dilation of local blood vessels and smooth muscle contraction, producing some of the symptoms of immediate hypersensitivity reactions. Antihistamines are drugs that counter histamine action.


Histocompatibility is literally the ability of tissues (Greek: histos) to get along with each other. It is used in immunology to describe the genetic systems that determine the rejection of tissue and organ grafts resulting from immunological recognition of histocompatibility (H) antigens.


see H-2.


see human immunodeficiency virus.


HLA, the acronym for Human Leukocyte Antigen, is the genetic designation for the human MHC. Individual loci are designated by upper-case letters, as in HLA-A, and alleles are designated by numbers, as in HLA-A*0201.


The invariant HLA-DM molecule in humans is involved in loading peptides onto MHC class II molecules. It is encoded in the MHC within a set of genes resembling MHC class II genes. A homologous protein in mice is called H-2M.

Hodgkin’s disease

Hodgkin’s disease is an immune system tumor characterized by large cells called Reed-Sternberg cells, which derive from mutated B-lineage cells. It exists in at least two polar forms, Hodgkin’s lymphoma and nodular sclerosis.


Homeostasis is a generic term describing the status of physiological normality. In the case of lymphocytes, homeostasis refers to an uninfected individual who has normal numbers of lymphocytes.

homologous recombination

Cellular genes can be disrupted by homologous recombination with copies of the gene into which erroneous sequences have been inserted. When these exogenous DNA fragments are introduced into cells, they recombine selectively with the cellular gene through remaining regions of sequence homology, replacing the functional gene with a nonfunctional copy.

Host-versus-graft disease

Host-versus-graft disease (HVGD) is another name for the allograft rejection reaction. The term is used mainly in relation to bone marrow transplantation.

human immunodeficiency virus

The human immunodeficiency virus (HIV) is the causative agent of the acquired immune deficiency syndrome (AIDS). HIV is a retrovirus of the lentivirus family that selectively infects macrophages and CD4 T cells, leading to their slow depletion, which eventually results in immunodeficiency.

Human leukocyte antigen

see HLA


Humanization is a term used to describe the genetic engineering of mouse hypervariable loops of a desired specificity into otherwise human antibodies. The DNA encoding hypervariable loops of mouse monoclonal antibodies or V regions selected in phage display libraries is inserted into the framework regions of human immunoglobulin genes. This allows the production of antibodies of a desired specificity that do not cause an immune response in humans treated with them.

Humoral immunity

Humoral immunity is the antibody-mediated specific immunity made in a humoral immune response. Humoral immunity can be transferred to unimmunized recipients by using immune serum containing specific antibody.


Monoclonal antibodies are most commonly produced from hybridomas. These are hybrid cell lines formed by fusing a specific antibody-producing B lymphocyte with a myeloma cell that is selected for its ability to grow in tissue culture and for an absence of immunoglobulin chain synthesis.

Hyperacute graft rejection

Hyperacute graft rejection of an allogenic tissue graft is an immediate reaction caused by natural preformed antibodies that react against antigens on the graft. The antibodies bind to endothelium and trigger the blood clotting cascade, leading to an engorged, ischemic graft and rapid loss of the organ.


Hypereosinophilia is an abnormal state in which there are extremely large numbers of eosinophils in the blood.


Repetitive immunization to achieve a heightened state of immunity is called hyperimmunization.

hypersensitivity reactions

Immune responses to innocuous antigens that lead to symptomatic reactions upon reexposure are called hypersensitivity reactions. These can cause hypersensitivity diseases if they occur repetitively. This state of heightened reactivity to antigen is called hypersensitivity. Hypersensitivity reactions are classified by mechanism: type I hypersensitivity reactions involve IgE antibody triggering of mast cells; type II hypersensitivity reactions involve IgG antibodies against cellsurface or matrix antigens; type III hypersensitivity reactions involve antigen:antibody complexes; and type IV hypersensitivity reactions are T cell-mediated.


The hypervariable (HV) regions of immunoglobulin and T-cell receptor V domains are small regions that make contact with the antigen and differ extensively from one receptor to the next. Cf. framework regions.



The inactive complement fragment iC3b is produced by cleavage of C3b and is the first step in C3b inactivation.


The ICAMs (intercellular adhesion molecules) are cell-surface ligands for the leukocyte integrins and are crucial in the binding of lymphocytes and other leukocytes to certain cells, including antigen-presenting cells and endothelial cells. They are members of the immunoglobulin superfamily. ICAM-1 is the most prominent ligand for the integrin CD11a:CD18 or LFA-1. It is rapidly inducible on endothelial cells by infection, and plays a major role in local inflammatory responses. ICAM-2 is constitutively expressed at relatively low levels by endothelium. ICAM-3 is expressed only on leukocytes and is thought to play an important part in adhesion between T cells and antigen-presenting cells, particularly dendritic cells.


All antibody molecules belong to a family of plasma proteins called immunoglobulins (Ig). Membrane-bound immunoglobulin serves as the specific antigen receptor on B lymphocytes.


Iccosomes are small fragments of membrane coated with immune complexes that fragment off the processes of follicular dendritic cells in lymphoid follicles early in a secondary or subsequent antibody response.


ICOS is a CD28-related protein that is induced on activated T cells and can enhance T-cell responses. It binds a ligand known as LICOS, which is distinct from the B7 molecules.


Each immunoglobulin molecule has the potential of binding a variety of antibodies directed at its unique features or idiotype. An idiotype is made up of a series of idiotopes from idiotype epitopes.

idiotypic network

Lymphocyte antigen receptors can recognize one another through idiotope–anti-idiotope interactions, forming an idiotypic network of receptors that may be important for the generation and maintenance of the receptor repertoire. The proposed components of idiotype networks exist, but their functional significance is uncertain.


see interferons.


Ig: standard abbreviation for immunoglobulin. Different immuno-globulin isotypes are called IgM, IgD, IgG, IgA, and IgE.

Igα, Igβ

B-cell antigen receptor.


IgA is the class of immunoglobulin characterized by α heavy chains. IgA antibodies are secreted mainly by mucosal lymphoid tissues.


IgD is the class of immunoglobulin characterized by δ heavy chains. It appears as surface immunoglobulin on mature naive B cells but its function is unknown.


IgE is the class of immunoglobulin characterized by ε heavy chains. It is involved in allergic reactions.


IgG is the class of immunoglobulin characterized by γ heavy chains. It is the most abundant class of immunoglobulin found in the plasma.


IgM is the class of immunoglobulin characterized by μ heavy chains. It is the first immunoglobulin to appear on the surface of B cells and the first to be secreted.


IL: see interleukins.

Immature B cells

Immature B cells are B cells that have rearranged a heavy- and a light-chain V-region gene and express surface IgM, but have not yet matured sufficiently to express surface IgD as well.

immature dendritic cells

Tissues throughout the body contain immature dendritic cells, which only leave the tissues in response to an inflammatory mediator or an infection. See also dendritic cells.

immediate reaction

During allergic reactions, there are normally two phases: the first happens almost immediately and is called the immediate reaction. Hypersensitivity reactions that occur within minutes of exposure to antigen are called immediate hypersensitivity reactions; such reactions are antibody mediated. Cf. delayed-type hypersensitivity.

immune clearance

When large amounts of antigen are injected into the blood, they are initially removed slowly by normal catabolic processes that also degrade plasma proteins. However, if the antigen elicits an antibody response, then antigen is removed at an accelerated rate as antigen:antibody complexes, a process known as immune clearance.

immune complex

The binding of antibody to a soluble antigen forms an immune complex. Large immune complexes form when sufficient antibody is available to cross-link the antigen; these are readily cleared by the reticuloendothelial system of cells bearing Fc and complement receptors. Small, soluble immune complexes that form when antigen is in excess can be deposited in and damage small blood vessels.

Immune deviation

Immune deviation is a term used to describe the polarization of an immune response to one dominated by TH1 or TH2 by the injection of antigen.

Immune modulation

Immune modulation is a general term encompassing various alterations in an immune response.

immune response

The immune response is the response made by the host to defend itself against a pathogen.

Immune response

Immune response (Ir) genes are genetic polymorphisms that control the intensity of the immune response to a particular antigen. Virtually all Ir phenotypes are due to the differential binding of peptide fragments of antigen to MHC molecules, especially MHC class II molecules. The term is little used now. An immune response (Ir) gene defect is usually, but not always, due to failure to bind an immunogenic peptide, so that no T-cell response is observed.

immune surveillance

It has been proposed that most tumors that arise are detected and eliminated by immune surveillance mediated by lymphocytes specific for tumor antigens. There is little evidence for the efficacy of this proposed process, but it remains an important concept in tumor immunology.

immune system

The immune system is the name used to describe the tissues, cells, and molecules involved in adaptive immunity, or sometimes the totality of host defense mechanisms.


Immunity is the ability to resist infection.


Immunization is the deliberate provocation of an adaptive immune response by introducing antigen into the body. See also active immunization; passive immunization.


Immunobiology is the study of the biological basis for host defense against infection.


Immunoblotting is a common technique in which proteins separated by gel electrophoresis are blotted onto a nitrocellulose membrane and revealed by the binding of specific labeled antibodies.

Immunodeficiency diseases

Immunodeficiency diseases are a group of inherited or acquired disorders in which some aspect or aspects of host defense are absent or functionally defective.


Immunodiffusion is the detection of antigen or antibody by the formation of an antigen:antibody precipitate in a clear agar gel.


Immunoelectrophoresis is a technique in which antigens are first separated by their electrophoretic mobility and are then detected and identified by immunodiffusion.


Immunofluorescence is a technique for detecting molecule using antibodies labeled with fluorescent dyes. The bound fluorescent antibody can be detected by microscopy, or by flow cytometry depending on the application being used. Indirect immunofluorescence uses anti-immunoglobulin antibodies labeled with fluorescent dyes to detect the binding of a specific unlabeled antibody.

immunofluorescent microscopy

There are three ways of detecting molecules in tissues: immunofluorescent microscopy that reveals the presence of any molecule against which you have a specific antibody; immunohistochemistry, in which one links an enzyme that produces a change in a molecule that is visible under the microscope; and immunoelectronmicroscopy, in which different sized gold particles are linked to antibodies and detected as bound gold particles.


Any molecule that can elicit an adaptive immune response on injection into a person or animal is called an immunogen. In practice, only proteins are fully immunogenic because only proteins can be recognized by T lymphocytes.


Immunogenetics was originally the analysis of genetic traits by means of antibodies against genetically polymorphic molecules such as blood group antigens or MHC proteins. Immunogenetics now refers to the genetic analysis, by any technique, of molecules important in immunology.

Immunoglobulin A

see IgA.

Immunoglobulin D

see IgD.

immunoglobulin domains

Many proteins are partly or entirely composed of protein domains known as immunoglobulin domains or Ig domains because they were first described in antibody molecules. Immunoglobulin domains are characteristic of proteins of the immunoglobulin superfamily, which includes antibodies, T-cell receptors, MHC molecules, and many other proteins described in this book. The immunoglobulin domain consists of a sandwich of two β sheets held together by a disulfide bond and called the immunoglobulin fold. There are two main types of immunoglobulin domain: C domains and V domains. Domains less closely related to the canonical Ig domains are sometimes also called immunoglobulin-like domains.

Immunoglobulin G

see IgG.

Immunoglobulin E

see IgE.

Immunoglobulin M

see IgM.

immunoglobulin repertoire

The immunoglobulin repertoire, also known as the antibody repertoire, is the total variety of immunoglobulin molecules in the body of an individual.

immunoglobulin superfamily

Many proteins involved in antigen recognition and cell–cell interaction in the immune system and other biological systems are members of a protein family called the immunoglobulin superfamily, or Ig superfamily, because their shared structural features were first defined in immunoglobulin molecules. All members of the immunoglobulin superfamily have at least one immunoglobulin or immunoglobulin-like domain.


The detection of antigens in tissues by means of visible products produced by the degradation of a colorless substrate by antibody-linked enzymes is called immunohistochemistry. This technique has the advantage that it can be combined with other stains to be viewed in the light microscope, whereas immunofluorescence microscopy requires a special dark-field or UV microscope.

Immunological ignorance

Immunological ignorance describes a form of self tolerance in which reactive lymphocytes and their target antigen are both detectable within an individual, yet no autoimmune attack occurs. Most autoimmune diseases probably reflect the loss of other lymphocytes known as regulatory or suppressor T cells.

immunological memory

When an antigen is encountered more than once, the adaptive immune response to each subsequent encounter is speedier and more effective, a crucial feature of protective immunity known as immunological memory. Immunological memory is specific for a particular antigen and is long-lived.

immunologically privileged sites

Allogeneic tissue placed in certain sites in the body, such as the brain, does not elicit graft rejection. Such sites are called immunologically privileged sites. Immunological privilege results from the effects of both physical barriers to cell and antigen migration, and soluble immunosuppressive mediators such as certain cytokines.


Immunology is the study of all aspects of host defense against infection and of adverse consequences of immune responses.


Immunophilins are proteins with peptidyl-prolyl cis–trans isomerase activity that bind the immunosuppressive drugs cyclosporin A, tacrolimus, and rapamycin.

immunoprecipitation analysis

Soluble proteins, or membrane proteins solubilized in detergents, can be labeled and then detected by immunoprecipitation analysis using specific antibodies. The immunoprecipitated labeled protein is usually detected by SDS-PAGE followed by autoradiography. When proteins that do not react directly with the antibody used are nevertheless precipitated, they are said to co-immunoprecipitate.

immunoreceptor tyrosine-based activation motifs

The T and B cell antigen receptors are associated with transmembrane molecules with immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domains. These tyrosine-containing motifs are sites of tyrosine phosphorylation and of association with tyrosine kinases and other phosphotyrosine-binding moieties involved in receptor signaling. Related motifs with opposing effects are immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which recruit phosphatases to the receptor site that remove the phosphate groups added by tyrosine kinases.


The ability of the immune system to sense and regulate its own responses is called immunoregulation.

immunosuppressive drugs

Compounds that inhibit adaptive immune responses are called immunosuppressive drugs. They are used mainly in the treatment of graft rejection and severe autoimmune disease.


Immunotoxins are antibodies that are chemically coupled to toxic proteins usually derived from plants or microbes. The antibody targets the toxin moiety to the required cells. Immunotoxins are being tested as anticancer agents and as immunosuppressive drugs.

indirect Coombs test

The indirect Coombs test is a variation of the direct Coombs test in which an unknown serum is tested for antibodies against normal red blood cells by first mixing the two and then washing out the serum from the red blood cells and reacting them with anti-immunoglobulin antibody. If antibody in the unknown serum binds to the red blood cells, agglutination by anti-immunoglobulin occurs.

Indirect immunofluorescence

see immunofluorescence.

inducible NO synthase

Macrophages and many other cells have an inducible NO synthase, or iNOS, that is induced by many different stimuli to activate NO synthesis. This is a major mechanism of host resistance to intracellular infection in mice, and probably in humans as well.

Infectious mononucleosis

Infectious mononucleosis, or glandular fever, is the common form of infection with the Epstein–Barr virus. It consists of fever, malaise, and swollen lymph nodes.


Inflammation is a general term for the local accumulation of fluid, plasma proteins, and white blood cells that is initiated by physical injury, infection, or a local immune response. This is also known as an inflammatory response. Acute inflammation is the term used to describe early and often transient episodes, whereas chronic inflammation occurs when the infection persists or during autoimmune diseases. Many different forms of inflammation are seen in different diseases. The cells that invade tissues undergoing inflammatory responses are often called inflammatory cells or an inflammatory infiltrate.

Influenza hemagglutinin

see hemagglutinin.

innate immunity

The early phases of the host response to infection depend on innate immunity in which a variety of innate resistance mechanisms recognize and respond to the presence of a pathogen. Innate immunity is present in all individuals at all times, does not increase with repeated exposure to a given pathogen, and discriminates between a group of related pathogens.

inositol trisphosphate

When inositol phospholipid is cleaved by phospholipase C-γ, it yields inositol trisphosphateIP3 and diacylglycerol. Inositol trisphosphate releases calcium ions from intracellular stores in the endoplasmic reticulum.

insulin-dependent diabetes mellitus

In insulin-dependent diabetes mellitus (IDDM), the β cells of the pancreatic islets of Langerhans are destroyed so that no insulin is produced. The disease is believed to result from an autoimmune attack on the β cells.


Integrins are heterodimeric cell-surface proteins involved in cell–cell and cell–matrix interactions. They are important in adhesive interactions between lymphocytes and antigen-presenting cells and in lymphocyte and leukocyte migration into tissues. The β1-integrins, or very late antigens (VLA), are a family of integrins with shared β1 chains and different α chains that mediate adhesion to other cells and to extracellular matrix proteins.

Intercellular adhesion molecules

see ICAMs.

Interdigitating reticular cells

see dendritic cells.


Interferons are cytokines that can induce cells to resist viral replication. Interferon-α (IFN) and interferon-β (IFN-β) are produced by leukocytes and fibroblasts, respectively, as well as by other cells, whereas interferon-γ (IFN-γ) is a product of CD4 TH1 cells, CD8 T cells, and NK cells. IFN-γ has as its primary action the activation of macrophages.


Interleukin, abbreviated IL, is a generic term for cytokines produced by leukocytes. We use the more general term cytokine in this book, but the term interleukin is used in the naming of specific cytokines such as IL-2. The interleukins are listed in Appendix III.


Interleukin-2 (IL-2) is the cytokine that is most central to the development of an adaptive immune response.

intracellular cytokine staining

Staining for cytokines in cells that produce them can be achieved by permiablizing the cell and reacting it with a labelled fluorescent anti-cytokine antibody. This procedure is called intracellular cytokine staining.


Injections can be administered by a number of routes: intracutaneous (intradermal)—entering the skin or dermis; subcutaneous—entering below the skin or dermis; intramuscular—entering the muscle; intranasal—by way of the nose; and intravenous—entering a vein.

Intrathymic dendritic cells

see dendritic cells.

The major histocompatibility complex

The major histocompatibility complex (MHC) class II proteins are assembled in the endoplasmic reticulum with the invariant chain (Ii), which is involved in shielding the MHC class II molecules from binding peptides and in delivering them to cellular vesicles. There Ii is degraded, leaving the MHC class II molecules able to bind peptide fragments of antigen.


ISCOMs are immune stimulatory complexes of antigen held within a lipid matrix that acts as an adjuvant and enables the antigen to be taken up into the cytoplasm after fusion of the lipid with the plasma membrane.

Isoelectric focusing

Isoelectric focusing is an electrophoretic technique in which proteins migrate in a pH gradient until they reach the place in the gradient at which their net charge is neutral—their isoelectric point. Uncharged proteins no longer migrate; thus each protein is focused at its isoelectric point.

isotype switching

The first antibodies produced in a humoral immune response are IgM, but activated B cells subsequently undergo isotype switching or class switching to secrete antibodies of different isotypes: IgG, IgA, and IgE. Isotype switching does not affect antibody specificity significantly, but alters the effector functions that an antibody can engage. Isotype switching occurs by recombination involving the deletion of DNA between the rearranged V region and the selected C-region exon at so-called S regions.


Immunoglobulins are made in several distinct isotypes or classes—IgM, IgG, IgD, IgA, and IgE—each of which has a distinct heavy-chain C region encoded by a distinct C-region gene. The isotype of an antibody determines the effector mechanisms that it can engage on binding antigen. The different heavy-chain C regions are encoded in exons 3′ to the V(D)J rearrangement site. This allows the same antibody heavy-chain V region to link up with different heavy-chain C-region isotypes as a result of somatic recombination.

Isotypic exclusion

Isotypic exclusion describes the use of one or other of the light-chain isotypes, κ or λ, by a given B cell or antibody.


J gene segments

The J gene segments, or joining gene segments, are found some distance 5′ to the C genes in immunoglobulin and T-cell receptor loci. A V and in the case of IgH chains, TCRβ chains and TCRδ chains, a D gene segment must also rearrange to a J gene segment to form a complete V-region exon.

Janus kinases

Cytokine receptors signal via Janus kinases (JAKs)—tyrosine kinases that are activated by the aggregation of cytokine receptors. These kinases phosphorylate proteins known as STATs, for Signal Transducers and Activators of Transcription. STATs are normally found in the cytosol, but move to the nucleus on phosphorylation and activate a variety of genes.

Junctional diversity

Junctional diversity is the diversity present in antigen-specific receptors that is created during the process of joining V, D, and J gene segments.


In the context of immunoglobulins, κ is one of the two classes of light-chain.

Killer activatory receptors

Killer activatory receptors (KARs) are cell-surface receptors on NK cells or cytotoxic T cells; they are receptors that can activate killing by these cells.

Killer T cell

Killer T cell is a commonly used term for cytotoxic T cell.

kinin system

The kinin system is an enzymatic cascade of plasma proteins that is triggered by tissue damage to produce several inflammatory mediators, including the vasoactive peptide bradykinin.


The cell-surface receptor c-Kit, present on developing B cells and other developing white blood cells, binds to the stem cell factor on bone marrow stromal cells. Kit has protein tyrosine kinase activity.

Kupffer cells

Kupffer cells are phagocytes lining the hepatic sinusoids; they remove debris and dying cells from the blood, but are not known to elicit immune responses.


In the context of immunoglobulins, λ is one of the two is one of the two classes of light-chain.


pre-B-cell receptor.

L chain

L chain: see light chain.

Langerhans’ cells

Langerhans’ cells are phagocytic dendritic cells found in the epidermis. They can migrate from the epidermis to regional lymph nodes via the afferent lymphatics. In the lymph node they differentiate into dendritic cells.

large pre-B cells

The large pre-B cells have a cell-surface pre-B-cell receptor, which is lost on the transition to small pre-B cells, in which light-chain gene rearrangement occurs.


see linker of activation in T cells.

late pro-B cell

The late pro-B cell is the stage in B-cell development in which VH to DJH joining occurs.


Some viruses can enter a cell but not replicate, a state known as latency. Latency can be established in various ways; when the virus is reactivated and replicates, it can produce disease.

late-phase reaction

In type I immediate hypersensitivity reactions, the late-phase reaction persists and is resistant to treatment with antihistamine.


The tyrosine kinase Lck associates most strongly with the cytoplasmic tails of CD4 and CD8. It plays a central role in signal transduction and activation of the T-cell receptor.


see lymphocytic choriomeningitis virus.


Lentiviruses are a group of retroviruses that include the human immunodeficiency virus, HIV-1. They cause disease after a long incubation period and can take years to become apparent.


Leprosy is caused by Mycobacterium leprae and occurs in a variety of forms. There are two polar forms: lepromatous leprosy, which is characterized by abundant replication of leprosy bacilli and abundant antibody production without cell-mediated immunity; and tuberculoid leprosy, in which few organisms are seen in the tissues, there is little or no antibody, but cell-mediated immunity is very active. The other forms of leprosy are intermediate between the polar forms.


Leukemia is the unrestrained proliferation of a malignant white blood cell characterized by very high numbers of the malignant cells in the blood. Leukemias can be lymphocytic, myelocytic, or monocytic.


Leukocyte is a general term for a white blood cell. Leukocytes include lymphocytes, polymorphonuclear leukocytes, and monocytes.

Leukocyte adhesion deficiency

Leukocyte adhesion deficiency is an immunodeficiency disease in which the common β chain of the leukocyte integrins is not produced. This mainly affects the ability of leukocytes to enter sites of infection with extracellular pathogens, so that infections cannot be effectively eradicated.

Leukocyte common antigen

see CD45.

leukocyte functional antigens

The leukocyte functional antigens or LFAs, are cell adhesion molecules initially defined with monoclonal antibodies: LFA-1 is a β2 integrin; LFA-2 is a member of the immunoglobulin superfamily, as is LFA-3, now called CD58. LFA-1 is particularly important in T-cell adhesion to endothelial cells and antigen-presenting cells.

Leukocyte integrins

see leukocyte functional antigens.


Leukocytosis is the presence of increased numbers of leukocytes in the blood. It is commonly seen in acute infection.


Leukotrienes are lipid mediators of inflammation that are derived from arachidonic acid. They are produced by macrophages and other cells.

LFA-1, LFA-2, LFA-3

see leukocyte functional antigens.


LICOS is the ligand for ICOS, a CD28-related protein that is induced on activated T cells and can enhance T-cell responses. LICOS is produced on activated dendritic cells, monocytes, and B cells.

light chain

The immunoglobulin light chain (L chain) is the smaller of the two types of polypeptide chain that make up all immunoglobulins. It consists of one V and one C domain, and is disulfide-bonded to the heavy chain. There are two classes of light chain, known as κ and λ.

Light zone

see germinal centers.

Linear epitope

see continuous epitopes.

linkage disequilibrium

Alleles at linked loci within the major histocompatibility complex are said to be in linkage disequilibrium if they are inherited together more frequently than predicted from their individual frequencies.

linked recognition

Epitopes recognized by B cells and helper T cells must be physically linked for the helper T cell to activate the B cell. This is called linked recognition.

linker of activation in T cells

The adaptor protein known as linker of activation in T cells (LAT) is a cytoplasmic protein with several tyrosines that become phosphorylated by the tyrosine kinase ZAP-70. It becomes associated with membrane lipid rafts and coordinates downstream signaling events in T-cell activation.

Low-zone tolerance

see high-zone tolerance.

molecule of bacterial lipopolysaccharide

A molecule of bacterial lipopolysaccharide (LPS) has first to be bound by the LPS-binding protein (LBP)) before it can interact with CD14, an LPS:LBP-binding protein on cells such as macrophages.


L-selectin is an adhesion molecule of the selectin family found on lymphocytes. L-selectin binds to CD34 and GlyCAM-1 on high endothelial venules to initiate the migration of naive lymphocytes into lymphoid tissue. Also called CD62L.

Lyme disease

Lyme disease is a chronic infection with Borrelia burgdorferi, a spirochete that can evade the immune response.


Lymph is the extracellular fluid that accumulates in tissues and is carried by lymphatic vessels back through the lymphatic system to the thoracic duct and into the blood.

Lymph nodes

Lymph nodes are a type of peripheral or secondary lymphoid organ. They are found in many locations thoughout the body where lymphatic vessels converge, and are sites where adaptive immune responses are initiated. Antigen-presenting cells and antigen delivered by the lymphatic vessels from a site of infection are displayed to the many recirculating lymphocytes that migrate through the lymph nodes. Some of these lymphocytes will recognize the antigen and respond to it, triggering an adaptive immune response.

lymphatic system

The lymphatic system is the system of lymphoid channels and tissues that drains extracellular fluid from the periphery via the thoracic duct to the blood. It includes the lymph nodes, Peyer’s patches, and other organized lymphoid elements apart from the spleen, which communicates directly with the blood.

Lymphatic vessels

Lymphatic vessels, or lymphatics, are thin-walled vessels that carry lymph through the lymphatic system.


A lymphoblast is a lymphocyte that has enlarged and increased its rate of RNA and protein synthesis.


All adaptive immune responses are mediated by lymphocytes. Lymphocytes are a class of white blood cells that bear variable cell-surface receptors for antigen. These receptors are encoded in rearranging gene segments. There are two main classes of lymphocyte—B lymphocytes (B cells) and T lymphocytes (T cells)—which mediate humoral and cell-mediated immunity, respectively. Small lymphocytes have little cytoplasm and condensed nuclear chromatin; on antigen recognition, the cell enlarges to form a lymphoblast and then proliferates and differentiates into an antigen-specific effector cell.

Lymphocyte function-associated antigens

see leukocyte functional antigens.

lymphocyte receptor repertoire

The lymphocyte receptor repertoire is the totality of the highly variable antigen receptors carried by B and T lymphocytes.

Lymphocytic choriomeningitis virus

Lymphocytic choriomeningitis virus (LCMV) is a virus that causes a nonbacterial meningitis in mice and occasionally in humans. It is used extensively in experimental studies.

lymphoid dendritic cells

Dendritic cells can arise from myeloid cells, in which case they are called myeloid dendritic cells, or from lymphoid tissues, in which case they are called lymphoid dendritic cells. Functional differences exist between these two lineages.

Lymphoid organs

Lymphoid organs are organized tissues characterized by very large numbers of lymphocytes interacting with a nonlymphoid stroma. The central or primary lymphoid organs, where lymphocytes are generated, are the thymus and bone marrow. The main peripheral or secondary lymphoid organs, in which adaptive immune responses are initiated, are the lymph nodes, spleen, and mucosal-associated lymphoid tissues such as tonsils and Peyer’s patches.


Lymphokines are cytokines produced by lymphocytes.


Lymphomas are tumors of lymphocytes that grow in lymphoid and other tissues but do not enter the blood in large numbers. There are many types of lymphoma, which represent the transformation of various developmental stages of B or T lymphocytes.


Lymphopoiesis is the differentiation of lymphoid cells from a common lymphoid progenitor.


Lymphotoxin (LT) is also known as tumor necrosis factor-β (TNF-β), a cytokine secreted by inflammatory CD4T cells that is directly cytotoxic for some cells.


see tyrosine kinase.


Lysosomes are acidified organelles that contain many degradative hydrolytic enzymes. Material taken up into endosomes is eventually delivered to lysosomes.

Lytic granules

Lytic granules containing perforin and granzymes are a defining characteristic of armed effector cytotoxic cells.


In the context of immunoglobulins, μ is the heavy chain of IgM.

M cells

Antigens and pathogens enter the body from the intestines through cells called microfold or M cells, which are specialized for this function. They are found over the gut-associated lymphoid tissue, or GALT. They may provide a route of infection for HIV.


Mac-1 is another name for the leukocyte integrin CD11b:CD18 (or complement receptor 2 (CR2)).


Macroglobulin describes plasma proteins that are globulins of high molecular weight, including immunoglobulin M (IgM) and α2-macroglobulin.

Macrophage activation

Resting macrophages will not destroy certain intracellular bacteria unless the macrophage is activated by a T cell. Macrophage activation is important in controlling infection and also causes damage to neighboring tissues.

macrophage mannose receptor

The macrophage mannose receptor is highly specific for certain carbohydrates that occur on the surface of some pathogens but not on host cells.


Macrophages are large mononuclear phagocytic cells important in innate immunity, in early non-adaptive phases of host defense, as antigen-presenting cells, and as effector cells in humoral and cell-mediated immunity. They are migratory cells deriving from bone marrow precursors and are found in most tissues of the body. They have a crucial role in host defense.


Dendritic cells are unique in being able to carry out macropinocytosis, a process in which large amounts of extracellular fluid are taken up in single vesicles. This is one means of antigen uptake.


MadCAM-1 is the mucosal cell adhesion molecule-1 or mucosal addressin that is recognized by the lymphocyte surface proteins L-selectin and VLA-4, allowing specific homing of lymphocytes to mucosal tissues.

major basic protein,

Eosinophils can be triggered to release their major basic protein, which can then act on mast cells to cause their degranulation.

major histocompatibility complex

The major histocompatibility complex (MHC) is a cluster of genes on human chromosome 6 or mouse chromosome 17. It encodes a set of membrane glycoproteins called the MHC molecules. The MHC class I molecules present peptides generated in the cytosol to CD8 T cells, and the MHC class II molecules present peptides degraded in intracellular vesicles to CD4 T cells. The MHC also encodes proteins involved in antigen processing and other aspects of host defense. The MHC is the most polymorphic gene cluster in the human genome, having large numbers of alleles at several different loci. Because this polymorphism is usually detected by using antibodies or specific T cells, the MHC molecules are often called major histocompatibility antigens.


see mucosal-associated lymphoid tissue.

mannan-binding lectin

The mannan-binding lectin (MBL), also called mannose-binding protein, is an acute-phase protein that binds to mannose residues. It can opsonize pathogens bearing mannose on their surfaces and can activate the complement system via the mannan-binding lectin pathway (MB-lectin pathway) an important part of innate immunity.

mantle zone

The follicular mantle zone is a rim of B lymphocytes that surrounds lymphoid follicles. The precise nature and role of mantle zone lymphocytes have not yet been determined.

MAP kinases

see mitogen-activated protein kinases.

marginal zone

The marginal zone of the lymphoid tissue of the spleen lies at the border of the white pulp. It contains a unique population of B cells, the marginal zone B cells, which do not circulate and are distinguished by a distinct set of surface proteins.


The components of the MB-lectin pathway of complement activation include two serine proteases, MASP-1 and MASP-2, that bind to mannan-binding lectin and play the same role in cleaving C4 as do C1r and C1s in the classical pathway.

Mast cells

Mast cells are large cells found in connective tissues throughout the body, most abundantly in the submucosal tissues and the dermis. They contain large granules that store a variety of mediator molecules including the vasoactive amine histamine. Mast cells have high-affinity Fcε receptors (FcεRI) that allow them to bind IgE monomers. Antigen-binding to this IgE triggers mast-cell degranulation and mast-cell activation, producing a local or systemic immediate hypersensitivity reaction. Mast cells have a crucial role in allergic reactions. Mastocytosis indicates an overproduction of mast cells.

Mature B cells

Mature B cells are B cells that have acquired surface IgM and IgD and have become able to respond to antigen.

MBL; MB-lectin pathway

see mannan-binding lectin.


The medulla is generally the central or collecting point of an organ. The thymic medulla is the central area of each thymic lobe, rich in bone marrow-derived antigen-presenting cells and the cells of a distinctive medullary epithelium. The medulla of the lymph node is a site of macrophage and plasma cell concentration through which the lymph flows on its way to the efferent lymphatics.

Membrane cofactor of proteolysis

Membrane cofactor of proteolysis (MCP or CD46) is a host-cell membrane protein that acts in conjunction with factor I to cleave C3b to its inactive derivative iC3b and thus prevent convertase formation.

membrane immunoglobulin

B cells carry on their surfaces many molecules of membrane immunoglobulin (mIg) of a single specificity, which acts as the receptor for antigen.

membrane-attack complex

The membrane-attack complex is made up of the terminal complement components, which assemble to generate a membrane-spanning hydrophilic pore, damaging the membrane.

Membranous glomerulonephritis

Membranous glomerulonephritis is a disease of the kidneys characterized by proteinuria and heavy deposits of antibody and complement.

Memory cells

Memory cells are the lymphocytes that mediate immunological memory. They are more sensitive to antigen than are naive lymphocytes and respond rapidly on reexposure to the antigen that originally induced them. Both memory B cells and memory T cells have been defined.

MHC; MHC class I; MHC class II

see major histocompatibility complex.

MHC class IB

The MHC class IB molecules encoded within the MHC are not highly polymorphic like the MHC class I and MHC class II molecules, and present a restricted set of antigens.

MHC class II compartment

The MHC class II compartment (MIIC) is a site in the cell where MHC class II molecules accumulate, encounter HLA-DM, and bind antigenic peptides, before migrating to the surface of the cell.

MHC class II transactivator

The protein that activates the transcription of MHC class II genes, the MHC class II transactivator (CIITA), is one of several defective genes in the disease bare lymphocyte syndrome, in which MHC class II molecules are lacking on all cells.

MHC congenic

Various specialized strains of mice are used to explore the role of MHC polymorphism in vivo. These are called MHC congenic, meaning that the mice differ only at the MHC complex, MHC recombinant, meaning that the mice have a crossover within the MHC, or MHC mutant, meaning that they are mutant at one or more loci.

MHC haplotype

MHC genes are inherited in most cases as an MHC haplotype, the set of genes in a haploid genome inherited from one parent. Thus, if the parents are designated as ab and cd, then the offspring are most likely to be ac, ad, bc, or bd.

MHC molecules

MHC molecules is the general name given to the highly polymorphic glycoproteins encoded by MHC class I and MHC class II genes, which are involved in the presentation of peptide antigens to T cells. They are also known as histocompatibility antigens.

MHC:peptide tetramers

The development of MHC:peptide tetramers held together by fluorescent streptavidin, which has four binding sites for the biotin attached to the tail of the MHC molecule, has made it possible to stain specific T cells in any species.

MHC-restricted antigen recognition

MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a given T cell will recognize a peptide antigen only when it is bound to a particular MHC molecule. Normally, as T cells are stimulated only in the presence of self MHC molecules, antigen is recognized only as peptides bound to self MHC molecules.

MIC molecules

MIC molecules are MHC class I-like molecules that are expressed in the gut under conditions of stress and are encoded within the class I region of the human MHC. They are not found in mice.

Microfold cells

M cells.


Microorganisms are microscopic organisms, unicellular except for some fungi, that include bacteria, yeasts and other fungi, and protozoa, all of which can cause human disease.


mIg: see membrane immunoglobulin.


Anti-carbohydrate antibodies can bind either the ends or the middles of polysaccharide chains; the latter antibodies are called middle-binders.


see MHC class II compartment.

Minor histocompatibility antigens

Minor histocompatibility antigens (minor H antigens) are peptides of polymorphic cellular proteins bound to MHC molecules that can lead to graft rejection when they are recognized by T cells.

Minor lymphocyte stimulatory

Minor lymphocyte stimulatory (Mls) loci: see Mls antigens.

Mitogen-activated protein kinases

Mitogen-activated protein kinases (MAP kinases) are kinases that become phosphorylated and activated on cellular stimulation by a variety of ligands, and lead to new gene expression by phosphorylating key transcription factors.

mixed lymphocyte reaction

When lymphocytes from two unrelated individuals are cultured together, the T cells proliferate in response to the allogeneic MHC molecules on the cells of the other donor. This mixed lymphocyte reaction is used in testing for histocompatibility.

Mls antigens

Mls antigens are non-MHC antigens that provoke strong primary mixed lymphocyte responses. They are encoded by minor lymphocyte stimulatory (Mls) loci, which are endogenous mammary tumor viruses integrated in the mouse genome. Mls antigens are encoded in the 3′ long terminal repeat of the integrated virus and act as superantigens. They stimulate a large number of T lymphocytes by binding to the Vb domain of all T-cell receptors bearing the Vb for which the superantigen is specific.


see mouse mammary tumor virus.

molecular mimicry

It has been proposed that infectious agents could provoke autoimmunity by molecular mimicry, the induction of antibodies and T cells that react against the pathogen but also cross-react with self antigens.

Monoclonal antibodies

Monoclonal antibodies are produced by a single clone of B lymphocytes. Monoclonal antibodies are usually produced by making hybrid antibody-forming cells from a fusion of nonsecreting myeloma cells with immune spleen cells.


Monocytes are white blood cells with a bean-shaped nucleus; they are precursors of macrophages.


Some antibodies recognize all allelic forms of a polymorphic molecule such as an MHC class I protein; these antibodies are thus said to recognize a monomorphic epitope.


An individual lymphocyte carries antigen receptors of a single antigen specificity and thus has the property of monospecificity in response to antigen.

Mouse mammary tumor virus

Mouse mammary tumor virus (MMTV) is a retrovirus that encodes a viral superantigen; integrated copies of related viruses encode the endogenous superantigens known as Mls antigens.


Mucins are highly glycosylated cell-surface proteins. Mucinlike molecules are bound by L-selectin in lymphocyte homing.

mucosal epithelia

All of the body’s internal epithelial organs are lined with epithelium that is coated with mucus, and are therefore called mucosal epithelia. This system is the site of entry for virtually all antigens, and is protected by a unique set of lymphoid organs.

mucosal-associated lymphoid tissue

The mucosal-associated lymphoid tissue (MALT) comprises all lymphoid cells in epithelia and in the lamina propria lying below the body’s mucosal surfaces. The main sites of mucosal-associated lymphoid tissues are the gut-associated lymphoid tissues (GALT), and the bronchial-associated lymphoid tissues (BALT).

Multiple myeloma

Multiple myeloma is a tumor of plasma cells, almost always first detected as multiple foci in bone marrow. Myeloma cells produce a monoclonal immunoglobulin, called a myeloma protein, that is detectable in the patient’s plasma.

Multiple sclerosis

Multiple sclerosis is a neurological disease characterized by focal demyelination in the central nervous system, lymphocytic infiltration in the brain, and a chronic progressive course. It is caused by an autoimmune response to various antigens found in the myelin sheath.

Myasthenia gravis

Myasthenia gravis is an autoimmune disease in which autoantibodies against the acetylcholine receptor on skeletal muscle cells cause a block in neuromuscular junctions, leading to progressive weakness and eventually death.

myeloid dendritic cells

Dendritic cells can arise from myeloid cells, in which case they are called myeloid dendritic cells, or from lymphoid tissues, in which case they are called lymphoid dendritic cells. Functional differences exist between these two lineages.

Myeloid progenitors

Myeloid progenitors are cells in bone marrow that give rise to the granulocytes and macrophages of the immune system.

Myeloma proteins

Myeloma proteins are immunoglobulins secreted by myeloma tumors and are found in the patient’s plasma.


Myelopoiesis is the production of monocytes and polymorphonuclear leukocytes in bone marrow.


Naive lymphocytes

Naive lymphocytes are lymphocytes that have never encountered their specific antigen and thus have never responded to it, as distinct from memory or effector lymphocytes. All lymphocytes leaving the central lymphoid organs are naive lymphocytes, those from the thymus being naive T cells and those from bone marrow being naive B cells.

Natural killer cells

Natural killer cells (NK cells) are large granular, non-T, non-B lymphocytes, which kill certain tumor cells. NK cells are important in innate immunity to viruses and other intracellular pathogens, as well as in antibody-dependent cell-mediated cytotoxicity (ADCC).


Necrosis is the death of cells or tissues due to chemical or physical injury, as opposed to apoptosis, which is a biologically programmed form of cell death. Necrosis leaves extensive cellular debris that needs to be removed by phagocytes, whereas apoptosis does not.

negative selection

During intrathymic development, thymocytes that recognize self are deleted from the repertoire, a process known as negative selection. Autoreactive B cells undergo a similar process in bone marrow.


Antibodies that can inhibit the infectivity of a virus or the toxicity of a toxin molecule are said to neutralize them. Such antibodies are known as neutralizing antibodies and the process of inactivation as neutralization.


Neutropenia describes the situation in which there are fewer neutrophils in the blood than normal.


Neutrophils, also known as neutrophilic polymorphonuclear leukocytes, are the major class of white blood cell in human peripheral blood. They have a multilobed nucleus and neutrophilic granules. Neutrophils are phagocytes and have an important role in engulfing and killing extracellular pathogens.


see nuclear factor of activated T cells.


The transcription factor called NFκB is made up of two chains of 50 kDa and 65 kDa. It is found under normal circumstances in the cytosol, where it is bound to a third chain called IκB, which is an inhibitor of NFκB transcription.

NK1.1 CD4 T cells

NK1.1 CD4 T cells are a small subset of T cells that express the NK1.1 marker, a molecule normally found on NK cells. NK1.1 T cells also express α:β T-cell receptors of limited diversity and either the co-receptor molecule CD4 or no co-receptor. They are enriched in the liver, and produce cytokines shortly after stimulation.

NK cells

natural killer cells.

Nodular sclerosis

see Hodgkin’s disease.


N-nucleotides are inserted into the junctions between gene segments of T-cell receptor and immunoglobulin heavy-chain V-region genes during gene segment joining. These N-regions are not encoded in either gene segment, but are inserted by the enzyme terminal deoxynucleotidyl transferase (TdT). They markedly increase the diversity of these receptors.

Recombination signal sequences

Recombination signal sequences (RSS) flanking gene segments consist of a seven-nucleotide heptamer and a nine-nucleotide nonamer of conserved sequence, separated by 12 or 23 nucleotides. RSSs form the target for the site-specific recombinase that joins the gene segments in antigen receptor gene rearrangement.

nonproductive rearrangements

When T- and B-cell receptor gene segments rearrange, they often form nonproductive rearrangements that cannot encode a protein because the coding sequences are in the wrong translational reading frame.


see N-nucleotides.

nuclear factor of activated T cells

The transcription factor called nuclear factor of activated T cells (NFAT) is a complex of a protein called NFATc, as it is held in the cytosol by serine/threonine phosphorylation, and the Fos/Jun dimer known as AP-1. It moves from the cytosol to the nucleus on cleavage of the phosphate residues by calcineurin, a serine/threonine protein phosphatase.


The nude mutation of mice produces hairlessness and defective formation of the thymic stroma, so that nude mice, which are homozygous for this mutation, have no mature T cells.


occupational allergy

When a person’s work induces allergy, this is called occupational allergy.


Oncogenes are genes involved in regulating cell growth. When these genes are defective in structure or expression, they can cause cells to grow continuously to form a tumor.

opportunistic pathogen

An opportunistic pathogen is a microorganism that causes disease only in individuals with compromised host defense mechanisms, as occurs in AIDS.


Opsonization is the alteration of the surface of a pathogen or other particle so that it can be ingested by phagocytes. Antibody and complement opsonize extracellular bacteria for destruction by neutrophils and macrophages.

oral tolerance

The feeding of foreign antigens leads typically to a state of specific and active unresponsiveness, a phenomenon known as oral tolerance.


An autoimmune disease that targets a specific organ is said to be organ-specific.

Original antigenic sin

Original antigenic sin describes the tendency of humans to make antibody responses to those epitopes shared between the original strain of a virus and subsequent related viruses, while ignoring other highly immunogenic epitopes on the second and subsequent viruses.



Lymphocyte subpopulations can be isolated by panning on petri dishes coated with monoclonal antibodies against cell-surface markers, to which the lymphocytes bind.

paracortical area

The paracortical area, or paracortex, is the T-cell area of lymph nodes, lying just below the follicular cortex, which is primarily composed of B cells.


Parasites are organisms that obtain sustenance from a live host. In medical practice, the term is restricted to worms and protozoa, the subject matter of parasitology.

Paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a disease in which complement regulatory proteins are defective, so that complement activation leads to episodes of spontaneous hemolysis.

Partial agonist peptides

see altered peptide ligands.

Passive hemagglutination

Passive hemagglutination is a technique for detecting antibody in which red blood cells are coated with antigen and the antibody is detected by agglutination of the coated red blood cells.

passive immunization

The injection of antibody or immune serum into a naive recipient is called passive immunization. Cf. active immunization.

Pathogenic microorganisms

Pathogenic microorganisms, or pathogens, are microorganisms that can cause disease when they infect a host.


Pathology is the scientific study of disease. The term pathology is also used to describe detectable damage to tissues.

pattern recognition receptors

The term pattern recognition receptors (PRRs) is used to define receptors that bind to pathogen-associated molecular patterns (PAMPs).

Pattern-recognition molecules

Pattern-recognition molecules are receptors of the innate immune system that recognize common molecular patterns on pathogen surfaces.


The cell-adhesion molecule PECAM (CD31) is found both on lymphocytes and at endothelial cell junctions. It is believed that CD31–CD31 interactions enable leukocytes to leave blood vessels and enter tissues.


Pentadecacatechol is the chemical substance in the leaves of the poison ivy plant that causes the cell-mediated immunity associated with hypersensitivity to poison ivy.


Pentraxins are a family of acute-phase proteins formed of five identical subunits, to which C-reactive protein and serum amyloid protein belong.


Perforin is a protein that can polymerize to form the membrane pores that are an important part of the killing mechanism in cell-mediated cytotoxicity. Perforin is produced by cytotoxic T cells and NK cells and is stored in granules that are released by the cell when it contacts a specific target cell.

periarteriolar lymphoid sheath

The periarteriolar lymphoid sheath (PALS) is part of the inner region of the white pulp of the spleen, and contains mainly T cells.

Peripheral blood mononuclear cells

Peripheral blood mononuclear cells are lymphocytes and monocytes isolated from peripheral blood, usually by Ficoll-Hypaque™ density centrifugation.


Peripheral or secondary lymphoid organs are the lymph nodes, spleen, and mucosal-associated lymphoid tissues, in which immune responses are induced, as opposed to the central lymphoid organs, in which lymphocytes develop.

Peripheral tolerance

Peripheral tolerance is tolerance acquired by mature lymphocytes in the peripheral tissues, as opposed to central tolerance, which is acquired by immature lymphocytes during their development.

Peyer’s patches

Peyer’s patches are aggregates of lymphocytes along the small intestine, especially the ileum.

phage display library

Antibody-like phage can be produced by cloning immunoglobulin V-region genes in filamentous phage, which thus express antigen-binding domains on their surfaces, forming a phage display library. Antigen-binding phage can be replicated in bacteria and used like antibodies. This technique can be used to develop novel antibodies of any specificity.


Phagocytosis is the internalization of particulate matter by cells. Usually, the phagocytic cells or phagocytes are macrophages or neutrophils, and the particles are bacteria that are taken up and destroyed. The ingested material is contained in a vesicle called a phagosome, which then fuses with one or more lysosomes to form a phagolysosome. The lysosomal enzymes are important in pathogen destruction and degradation to small molecules.

Phosphatidylinositol bisphosphate

Phosphatidylinositol bisphosphatePIP2 is a membrane-associated phospholipid that is cleaved by phospholipase C-γ to give the signaling molecules diacylglycerol and inositol trisphosphate.

Phospholipase C-γ

Phospholipase C-γ is a key enzyme in signal transduction. It is activated by protein tyrosine kinases that are themselves activated by receptor ligation, and activated phospholipase C-γ cleaves inositol phospholipid into inositol trisphosphate and diacylglycerol.


Plasma is the fluid component of blood containing water, electrolytes, and the plasma proteins.

Plasma cells

Plasma cells are terminally differentiated B lymphocytes and are the main antibody-secreting cells of the body. They are found in the medulla of the lymph nodes, in splenic red pulp, and in bone marrow.


A plasmablast is a B cell in a lymph node that already shows some features of a plasma cell.

Platelet activating factor

Platelet activating factor (PAF) is a lipid mediator that activates the blood clotting cascade and several other components of the innate immune system.


Platelets are small cell fragments found in the blood that are crucial for blood clotting. They are formed from megakaryocytes.


P-nucleotides are nucleotides found in junctions between gene segments of the rearranged V-region genes of antigen receptors. They are an inverse repeat of the sequence at the end of the adjacent gene segment, being generated from a hairpin intermediate during recombination, and hence are called palindromic or P-nucleotides.

Poison ivy

Poison ivy is a plant whose leaves contain pentadecacatechol, a potent contact sensitizing agent and a frequent cause of contact hypersensitivity.

polyclonal activation

Antigen activates specific lymphocytes, whereas all mitogens, by definition, activate most or all lymphocytes, a process known as polyclonal activation because it involves multiple clones of diverse specificity. Such mitogens are known as polyclonal mitogens.


The major histocompatibility complex is both polygenic, containing several loci encoding proteins of identical function, and polymorphic, having multiple alleles at each locus.

poly-Ig receptor

The poly-Ig receptor binds polymeric immunoglobulins, especially IgA, at the basolateral membrane of epithelia and transports them across the cell, where they are released from the apical surface. This transcytosis transfers IgA from its site of synthesis to its site of action at epithelial surfaces.

polymerase chain reaction

The polymerase chain reaction or PCR uses high temperature and unique thermostable enzymes to replicate DNA. It has revolutionized molecular biology.


Polymorphism literally means existing in a variety of different shapes. Genetic polymorphism is variability at a gene locus in which the variants occur at a frequency of greater than 1%. The major histocompatibility complex is the most polymorphic gene cluster known in humans.

Polymorphonuclear leukocytes

Polymorphonuclear leukocytes are white blood cells with multilobed nuclei and cytoplasmic granules. There are three types of polymorpho-nuclear leukocyte: the neutrophils with granules that stain with neutral dyes, the eosinophils with granules that stain with eosin, and the basophils with granules that stain with basic dyes.


Some antibodies show polyspecificity, the ability to bind to many different antigens. This is also known as polyreactivity.

positive selection

Only those developing T cells whose receptors can recognize antigens presented by self MHC molecules can mature in the thymus, a process known as positive selection. All other developing T cells die before reaching maturity.

pre-B-cell receptor

Expression of the pre-B-cell receptor, or pre-B-cell receptor complex, is a critical event in B-cell development. Expression of this receptor, which is a complex of at least five proteins, causes the pre-B cell to enter the cell cycle, to turn off the RAG genes, to degrade the RAG proteins, and to expand by several cell divisions. Then the signal ceases, and the pre-B cell is ready to rearrange its light chains.

pre-B cells

During B-cell development, pre-B cells are cells that have rearranged their heavy-chain genes but not their light-chain genes.

precipitin reaction

The precipitin reaction was the first quantitative technique for measuring antibody production. The amount of antibody is determined from the amount of precipitate obtained with a fixed amount of antigen. The precipitin reaction also can be used to define antigen valence and zones of antibody or antigen excess in mixtures of antigen and antibody.


Prednisone is a synthetic steroid with potent anti-inflammatory and immunosuppressive activity used in treating acute graft rejection, autoimmune disease, and lymphoid tumors.

thymocytes pair with a surrogate α chain called pTα

In T-cell development, TCR β chains expressed by CD44lowCD25+thymocytes pair with a surrogate α chain called pTα (pre-T-cell α) to form a pre-T-cell receptor that exits the endoplasmic reticulum via the Golgi as a complex with the CD3 molecules.

primary focus

During T-dependent antibody responses, a primary focus of B-cell activation forms in the vicinity of the margin between T and B cell areas of lymphoid tissue. Here, the T and B cells interact and B cells can differentiate directly into antibody-forming cells or migrate to lymphoid follicles for further proliferation and differentiation.

primary follicles

Lymphoid tissues contain lymphoid follicles made up of follicular dendritic cells and B lymphocytes. The primary follicles contain resting B lymphocytes and are the site at which germinal centers form when they are entered by activated B cells, forming secondary follicles.

primary immune response

The primary immune response is the adaptive immune response to an initial exposure to antigen. Primary immunization, also known as priming, generates both the primary immune response and immunological memory.

primary interaction

The binding of antibody molecules to antigen is called a primary interaction, as distinct from secondary interactions in which binding is detected by some associated change such as the precipitation of soluble antigen or agglutination of particulate antigen.

Primary lymphoid organ

see central lymphoid organ.


Priming of antigen-specific naive lymphocytes occurs when antigen is presented to them in an immunogenic form; the primed cells will differentiate either into armed effector cells or into memory cells that can respond in second and subsequent immune responses.

pro-B cells

During B-cell development, pro-B cells are cells that have displayed B-cell surface marker proteins but have not yet completed heavy-chain gene rearrangement. They are divided into early pro-B cells and late pro-B cells.

Productive rearrangements

Any lymphocyte receptor chain can be rearranged in either of two ways, productive and nonproductive. Productive rearrangements are in the correct reading frame for the receptor chain in question.


Progenitors are the more differentiated progeny of stem cells that give rise to distinct subsets of mature blood cells and lack the capacity for self-renewal posssed by true stem cells.

Programmed cell death

see apoptosis.


see factor P.


Prostaglandins, like leukotrienes, are lipid products of the metabolism of arachidonic acid that have a variety of effects on a variety of tissues, including activities as inflammatory mediators.


Cytosolic proteins are degraded by a large catalytic multisubunit protease called a proteasome. It is thought that peptides that are presented by MHC class I molecules are generated by the action of proteasomes, and two interferon-inducible subunits of some proteasomes are encoded in the MHC.


Protectin (CD59) is a cell-surface protein that protects host cells from being damaged by complement. It inhibits the formation of the membrane-attack complex by preventing the binding of C8 and C9 to the C5b,6,7 complex.

Protective immunity

Protective immunity is the resistance to specific infection that follows infection or vaccination.

Protein A

Protein A is a membrane component of Staphylococcus aureus that binds to the Fc region of IgG and is thought to protect the bacteria from IgG antibodies by inhibiting their interactions with complement and Fc receptors. It is useful for purifying IgG antibodies.

Protein kinase C

Protein kinase C (PKC) is a family of serine/threonine kinases that are activated by diacylglycerol and calcium as a result of signaling via many different receptors.

Protein kinases

Protein kinases add phosphate groups to proteins, and protein phosphatases remove these phosphate groups. Enzymes that add phosphate groups to tyrosine residues are called protein tyrosine kinases. These enzymes have crucial roles in signal transduction and regulation of cell growth. Their activity is regulated by a second set of molecules called protein tyrosine phosphatases that remove the phosphate from the tyrosine residues.


Proto-oncogenes are cellular genes that regulate growth control. When mutated or aberrantly expressed, they can contribute to the malignant transformation of cells, leading to cancer. Cf. oncogenes.


A provirus is the DNA form of a retrovirus when it is integrated into the host cell genome, where it can remain transcriptionally inactive for long periods of time.




see pre-T-cell receptor.

pulmonary surfactant A

The pulmonary surfactant A and D proteins are members of the pentraxin family that play various roles in the acute-phase response.

Purine nucleotide phosphorylase

Purine nucleotide phosphorylase (PNP) deficiency is an enzyme defect that results in severe combined immunodeficiency. This enzyme is important in purine metabolism, and its deficiency causes the accumulation of purine nucleosides, which are toxic for developing T cells, causing the immune deficiency.


Pus is the mixture of cell debris and dead neutrophils that is present in wounds and abscesses infected with extracellular encapsulated bacteria.

pyogenic bacteria

Bacteria with large capsules are difficult for phagocytes to ingest. Such encapsulated bacteria often produce pus at the site of infection, and are thus called pyogenic bacteria. Pyogenic organisms used to kill many young people. Now, pyogenic infections are largely limited to the elderly.

12/23 rule

The 12/23 rule states that gene segments of immunoglobulin or T-cell receptors can be joined only if one has a recognition signal sequence with a 12 base pair spacer, and the other has a 23 base pair spacer.



see small G proteins.

Radiation bone marrow chimeras

Radiation bone marrow chimeras are mice that have been heavily irradiated and then reconstituted with bone marrow cells of a different strain of mouse, so that the lymphocytes differ genetically from the environment in which they develop. Such chimeric mice have been important in studying lymphocyte development.


Antigen–antibody interaction can be studied by radioimmunoassay (RIA) in which antigen or antibody is labeled with radioactivity. An unlabeled antigen or antibody is attached to a solid support such as a plastic surface, and the fraction of the labeled antibody or antigen retained on the surface is determined in order to measure binding.


see small G proteins.


The recombination activating genes RAG-1 and RAG-2 encode the proteins RAG-1 and RAG-2, which are critical to receptor gene rearrangement. Mice lacking either of these genes cannot form receptors and thus have no lymphocytes.


Rapamycin, or sirolimus, is an immunosuppressive drug that blocks cytokine action.


see small G proteins.


Antigen receptor expression requires gene segment rearrangement in developing lymphocytes. The expressed V-region sequences are composed of rearranged gene segments.

receptor editing

The replacement of a light chain of a self-reactive antigen receptor on immature B cells with a light chain that does not confer autoreactivity is known as receptor editing. This has also been shown with heavy chains.

receptor-associated tyrosine kinases

The antigen receptors of lymphocytes are associated with receptor-associated tyrosine kinases, mainly of the Src family, which bind to receptor tails via their SH2 domains.

Receptor-mediated endocytosis

Receptor-mediated endocytosis is the internalization into endosomes of molecules bound to cell-surface receptors. Antigens bound to B-cell receptors are internalized by this process.

recessive lethal gene

A recessive lethal gene encodes a protein that is needed for the human or animal to develop to adulthood; when both copies are defective, the human or animal dies in utero or early after birth.


In any situation in which cells or tissues are transplanted, they come from a donor and are placed in a recipient or host.

Recombination activating genes

see RAG-1 and RAG-2.

Recombination signal sequences

Recombination signal sequences (RSSs) are short stretches of DNA that flank the gene segments that are rearranged to generate a V-region exon. They always consist of a conserved heptamer and nonamer separated by 12 or 23 base pairs. Gene segments are only joined if one is flanked by an RSS containing a 12 base pair spacer and the other is flanked by an RSS containing a 23 base pair spacer—the 12/23 rule of gene segment joining.

red pulp

The nonlymphoid area of the spleen in which red blood cells are broken down is called the red pulp.

Reed-Sternberg cells

Reed-Sternberg cells are large malignant B cells that are found in Hodgkin’s disease.


Regulatory or suppressor T cells can inhibit T-cell responses.

respiratory burst

When neutrophils and macrophages take up opsonized particles, this triggers a metabolic change in the cell called the respiratory burst. It leads to the production of a number of mediators.

respiratory syncytial virus

The virus known as respiratory syncytial virus (RSV) is a human pathogen that is a common cause of severe chest infection in young children, often associated with wheezing, as well as in immuno-compromised patients and patients with AIDS.


The Rev protein is the product of the rev gene of the human immuno-deficiency virus (HIV). The Rev protein promotes the passage of viral RNA from nucleus to cytoplasm during HIV replication.

reverse transcriptase

The enzyme reverse transcriptase is an essential component of retroviruses, as it translates the RNA genome into DNA before integration into host cell DNA. Reverse transcriptase also enables RNA sequences to be converted into complementary DNA (cDNA), and so to be cloned, and thus is an essential reagent in molecular biology.

reverse transcriptase–polymerase chain reaction

The reverse transcriptase–polymerase chain reaction (RT-PCR) is used to amplify RNA sequences. The enzyme reverse transcriptase is used to convert an RNA sequence into a cDNA sequence, which is then amplified by PCR.


The Rhesus (Rh) blood group antigen is a red cell membrane antigen that is also detectable on the red blood cells of rhesus monkeys. Anti-Rh antibodies do not agglutinate human red blood cells, so antibody to Rh antigen must be detected by using a Coombs test.

Rheumatic fever

Rheumatic fever is caused by antibodies elicited by infection with some Streptococcus species. These antibodies cross-react with kidney, joint, and heart antigens.

Rheumatoid arthritis

Rheumatoid arthritis is a common inflammatory joint disease that is probably due to an autoimmune response. The disease is accompanied by the production of rheumatoid factor, an IgM anti-IgG antibody that can also be produced in normal immune responses.


sandwich ELISA

The technique of sandwich ELISA uses antibody bound to a surface to trap a protein by binding to one of its epitopes. The trapped protein is then detected by an enzyme-linked antibody specific for a different epitope on the protein’s surface. This gives the assay a high degree of specificity.

Scatchard analysis

Scatchard analysis is a mathematical analysis of equilibrium binding that allows the affinity and valence of a receptor–ligand interaction to be determined.

Scavenger receptors

Scavenger receptors on macrophages and other cells bind to numerous ligands and remove them from the blood. The Kupffer cells in the liver are particularly rich in scavenger receptors.

SCID, scid

see severe combined immunodeficiency.


SDS-PAGE is the common abbreviation for polyacrylamide gel electrophoresis (PAGE) of proteins dissolved in the detergent sodium dodecyl sulfate (SDS). This technique is widely used to characterize proteins, especially after labeling and immunoprecipitation.

secondary antibody response

A secondary antibody response is the antibody response induced by a second or booster injection of antigen—a secondary immunization. The secondary response starts sooner after antigen injection, reaches higher levels, is of higher affinity than the primary response, and is dominated by IgG antibodies. Therefore, the response to each immunization is increasingly intense, so the secondary, tertiary, and subsequent responses are of increasing magnitude.

second set rejection

When the recipient of a first tissue or organ graft has rejected that graft, a second graft from the same donor is rejected more rapidly and vigorously in what is called a second set rejection.

second signal

The co-stimulatory signal required for lymphocyte activation is often called a second signal, with the first signal coming from the binding of antigen by the antigen receptor. Both signals are required for the activation of most lymphocytes.

Secondary interactions

see primary interactions.

secretory component

The secretory component attached to IgA antibodies in body secretions is a fragment of the poly-Ig receptor left attached to the IgA after transport across epithelial cells.


A cell is said to be selected by antigen when its receptors bind that antigen. If the cell starts to proliferate as a result, this is called clonal selection, and the cell founds a clone; if the cell is killed as a result of binding antigen, this is called negative selection or clonal deletion.


Selectins are a family of cell-surface adhesion molecules of leukocytes and endothelial cells that bind to sugar moieties on specific glycoproteins with mucinlike features.

self antigens

Antigens in the body of an individual are by convention called self antigens. Lymphocytes are screened during their immature stages for reactivity with self antigens, and those that do respond undergo apoptosis.

self tolerance

Tolerance is the failure to respond to an antigen; when that antigen is borne by self tissues, tolerance is called self tolerance. See also tolerance.


Allergic reactions require prior immunization, called sensitization, by the allergen that elicits the acute response. Allergic reactions occur only in sensitized individuals.


Sepsis is infection of the bloodstream. This is a very serious and frequently fatal condition. Infection of the blood with gram-negative bacteria triggers septic shock through the release of the cytokine TNF-α.

sequence motif

A sequence motif is a pattern of nucleotides or amino acids shared by different genes or proteins that often have related functions. Sequence motifs observed in peptides that bind a particular MHC glycoprotein are based on the requirements for particular amino acids to achieve binding to that MHC molecule.


Seroconversion is the phase of an infection when antibodies against the infecting agent are first detectable in the blood.


Serology is the use of antibodies to detect and measure antigens using serological assays, so called because these assays were originally carried out with serum, the fluid component of clotted blood, from immunized individuals.


Mast cells in mice store the small soluble mediator serotonin in their granules.


Different strains of bacteria and other pathogens can sometimes be distinguished by their serotype, the ability of an immune serum to agglutinate or lyse some strains of bacteria and not others.


Serpins are a large family of protease inhibitors.


Serum is the fluid component of clotted blood.

Serum sickness

Serum sickness occurs when foreign serum or serum proteins are injected into a person. It is caused by the formation of immune complexes between the injected protein and the antibodies formed against it. It is characterized by fever, arthralgias, and nephritis.

Severe combined immune deficiency

Severe combined immune deficiency (SCID) is an immune deficiency disease in which neither antibody nor T-cell responses are made. It is usually the result of T-cell deficiencies. The scid mutation causes severe combined immune deficiency in mice.

SH2 domain

see Src-family tyrosine kinases.

signal joint

A signal joint is formed by the precise joining of recognition signal sequences in the process of somatic recombination that generates T-cell receptor and immunoglobulin genes.

Signal transducers and activators of transcription

Signal transducers and activators of transcription (STATs): see Janus kinases.

Signal transduction

Signal transduction describes the general process by which cells perceive changes in their environment. In lymphocytes, the most important changes are those occurring during infection that generate antigens that stimulate the cells of the immune system to bring about an adaptive immune response.

single-chain Fv

A single-chain Fv fragment, comprising a V region of a heavy chain linked by a stretch of synthetic peptide to a V region of a light chain, can be made by genetic engineering.

single-positive thymocytes

During T-cell maturation in the thymus, mature T cells are detected by the expression of either the CD4 or the CD8 co-receptor and are therefore called single-positive thymocytes.


Sirolimus is the drug name that has been adopted for the chemical rapamycin; the two terms are used interchangeably in the literature.


The chemokine known as SLC is produced by lymphatic vessels and attracts dendritic cells.

Small G proteins

Small G proteins are monomeric G proteins such as Ras, that act as intracellular signaling molecules downstream of many transmembrane signaling events. They bind GTP in their active form, and hydrolyze it to GDP to become inactive.

Small pre-B cells

see large pre-B cells.


Smallpox is an infectious disease, caused by the virus variola, that once killed at least 10% of infected people. It has now been eradicated by vaccination.

somatic diversification theory

When immunologists discovered that antibodies were variable, they entertained various theories, including the somatic diversification theory that postulated that the genes for immunoglobulin were constant, and that they diversified in somatic cells. This turned out to be partly true, as somatic hypermutation is now well established. However, other theories were needed to explain other features of antibody diversity, including somatic gene rearrangement and isotype switching.

Somatic gene therapy

see gene therapy.

somatic hypermutation,

During B-cell responses to antigen, the V-region DNA sequence undergoes somatic hypermutation, resulting in the generation of variant immunoglobulins, some of which bind antigen with a higher affinity. This allows the affinity of the antibody response to increase. These mutations affect only somatic cells, and are not inherited through germline transmission.

somatic recombination

During lymphocyte development, receptor gene segments undergo somatic recombination to generate intact V-region exons that encode the V region of each immunoglobulin and T-cell receptor chain. These events occur only in somatic cells; the changes are not inherited.


see 12-23 rule.


The specificity of an antibody determines its ability to distinguish the immunogen from other antigens.


One uses spectratyping to define certain types of DNA gene segments that give a repetitive spacing of three nucleotides, or one codon.


The spleen is an organ in the upper left side of the peritoneal cavity containing a red pulp, involved in removing senescent blood cells, and a white pulp of lymphoid cells that respond to antigens delivered to the spleen by the blood.

Src-family tyrosine kinases

The Src-family tyrosine kinases are receptor-associated protein tyrosine kinases. They have several domains, called Src-homology 1, 2, and 3. The SH1 domain contains the active site of the kinase, the SH2 domain can bind to phosphotyrosine residues, and the SH3 domain is involved in interactions with proline-rich regions in other proteins.

Staphylococcal enterotoxins

Staphylococcal enterotoxins (SEs) cause food poisoning and also stimulate many T cells by binding to MHC class II molecules and the Vb domain of certain T-cell receptors; the staphylococcal enterotoxins are thus superantigens.


see Janus kinases.

Stem-cell factor

Stem-cell factor (SCF) is a transmembrane protein on bone marrow stromal cells that binds to c-Kit, a signaling receptor carried on developing B cells and other developing white blood cells.

stromal cells

The development of B lymphocytes and T lymphocytes occurs in association with stromal cells, which provide various soluble and cell-bound signals to the developing lymphocyte.


Antigens can be injected into the subcutaneous layer to induce an adaptive immune response. See also intracutaneous.


Superantigens are molecules that stimulate a subset of T cells by binding to MHC class II molecules and Vb domains of T-cell receptors, stimulating the activation of T cells expressing particular Vb gene segments. The staphylococcal enterotoxins are one of the sources of superantigens.

Suppressor T cells

see regulatory T cells.

surface immunoglobulin

The membrane-bound immunoglobulin that acts as the antigen receptor on B cells is often known as surface immunoglobulin (sIg).

surrogate light chain

The surrogate light chain is made up of two molecules called VpreB and λ5. Together, this chain can pair with an in-frame heavy chain, move to the cell surface, and signal for pre-B-cell growth.

switch region

When isotype switching occurs, the active heavy-chain V-region exon undergoes somatic recombination with a 3′ constant-region gene at a switch region of DNA. These DNA joints do not need to occur at precise sites, because they occur in intronic DNA. Thus, all switch recombinations are productive.


see tyrosine kinase.

sympathetic ophthalmia

When one eye is damaged, there is often an autoimmune response that damages the other eye, a syndrome known as sympathetic ophthalmia.

syngeneic graft

A syngeneic graft is a graft between two genetically identical individuals. It is accepted as self.

Systemic anaphylaxis

Systemic anaphylaxis is the most dangerous form of immediate hypersensitivity reaction. It involves antigen in the bloodstream triggering mast cells all over the body. The activation of these mast cells causes widespread vasodilation, tissue fluid accumulation, epiglottal swelling, and often death.

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease in which autoantibodies against DNA, RNA, and proteins associated with nucleic acids form immune complexes that damage small blood vessels, especially of the kidney.


T cells

T cells, or T lymphocytes, are a subset of lymphocytes defined by their development in the thymus and by heterodimeric receptors associated with the proteins of the CD3 complex. Most T cells have α:β heterodimeric receptors but γ:δ T cells have a γ:δ heterodimeric receptor.


TACI (transmembrane activator and CAML-interactor) is a member of the TNF-receptor family and is one of two major receptors for BLyS. It is found on B cells, dendritic cells, and T cells and is probably the important receptor for receiving signals from BLyS.


Tacrolimus, or FK506, is an immunosuppressive polypeptide drug that inactivates T cells by inhibiting signal transduction from the T-cell receptor. Tacrolimus and cyclosporin A are the most commonly used immunosuppressive drugs in organ transplantation.


TAP1 and TAP2 (transporters associated with antigen processing) are ATP-binding cassette proteins involved in transporting short peptides from the cytosol into the lumen of the endoplasmic reticulum, where they associate with MHC class I molecules.


Tapasin, or the TAP-associated protein, is a key molecule in the assembly of MHC class I molecules; a cell deficient in this protein has only unstable MHC class I molecules on the cell surface.

target cells

The functions of effector T cells are always assayed by the changes that they produce in antigen-bearing target cells. These cells can be B cells, which are activated to produce antibody; macrophages, which are activated to kill bacteria or tumor cells; or labeled cells that are killed by cytotoxic T cells.


The Tat protein is a product of the tat gene of HIV. It is produced when latently infected cells are activated, and it binds to a transcriptional enhancer in the long terminal repeat of the provirus, increasing the transcription of the proviral genome.

T-cell antigen receptor

see T-cell receptor.

T-cell clone

A T-cell clone is derived from a single progenitor T cell. See also cloned T-cell line.

T-cell hybrids

T-cell hybrids are formed by fusing an antigen-specific, activated T cell with a T-cell lymphoma. The hybrid cells bear the receptor of the specific T-cell parent and grow in culture like the lymphoma.

T-cell lines

T-cell lines are cultures of T cells grown by repeated cycles of stimulation, usually with antigen and antigen-presenting cells. When single T cells from these lines are propagated, they can give rise to T-cell clones or cloned T-cell lines.

T-cell receptor

The T-cell receptor (TCR) consists of a disulfide-linked heterodimer of the highly variable α and β chains expressed at the cell membrane as a complex with the invariant CD3 chains. T cells carrying this type of receptor are often called α:β T cells. An alternative receptor made up of variable γ and δ chains is expressed with CD3 on a subset of T cells. Both of these receptors are expressed with a disulfide-linked homodimer of ζ chains.

T-cell zones

The T-cell zones in lymphoid tissues are enriched in T cells and are distinct from the B-cell zones and the stromal elements.

Tec kinase

Activation of the lymphocyte antigen receptors is linked to activation of PLC-γ through members of the Tec kinase family of src-like tyrosine kinases. Other Tec kinases are Btk in B cells, which is mutated in the human immunodeficiency disease X-linked agammaglobulinemia (XLA), and Itk in T lymphocytes.

terminal complement components,

The complement system can be activated directly or by antibody, but both pathways converge with the activation of the terminal complement components, which may assemble to form the membraneattack complex.

terminal deoxynucleotidyl transferase

The enzyme terminal deoxynucleotidyl transferase (TdT) inserts nontemplated or N-nucleotides into the junctions between gene segments in T-cell receptor and immunoglobulin V-region genes. The N-nucleotides contribute greatly to junctional diversity in V regions.

tertiary response

When the same antigen is injected a third time, the response elicited is called a tertiary response and the injection a tertiary immunization.

TH1 cells

TH1 cells are a subset of CD4 T cells that are characterized by the cytokines they produce. They are mainly involved in activating macrophages, and are sometimes called inflammatory CD4 T cells.

TH2 cells

TH2 cells are a subset of CD4 T cells that are characterized by the cytokines they produce. They are mainly involved in stimulating B cells to produce antibody, and are often called helper CD4 T cells.

TH3 cell

The term TH3 cell has been used to describe unique cells that produce mainly transforming growth factor-β in response to antigen; they develop predominantly in the mucosal immune response to antigens that are presented orally.

thoracic duct

The lymph from most of the body, except the head, neck, and right arm, is gathered in a large lymphatic vessel, the thoracic duct, which runs parallel to the aorta through the thorax and drains into the left subclavian vein. The thoracic duct thus returns the lymphatic fluid and lymphocytes back into the peripheral blood circulation.


Surgical removal of the thymus is called thymectomy.

thymic anlage

The thymic anlage is the tissue from which the thymic stroma develops during embryogenesis.

thymic cortex

The thymic cortex is the outer region of each thymic lobule in which thymic progenitor cells proliferate, rearrange their T-cell receptor genes, and undergo thymic selection, especially positive selection on thymic cortical epithelial cells.

thymic stroma

The thymic stroma consists of epithelial cells and connective tissue that form the essential microenvironment for T-cell development.


Thymocytes are lymphoid cells found in the thymus. They consist mainly of developing T cells, although a few thymocytes have achieved functional maturity.


The thymus, the site of T-cell development, is a lymphoepithelial organ in the upper part of the middle of the chest, just behind the breastbone.

thymus-dependent antigens

Some antigens elicit responses only in individuals that have T cells; they are called thymus-dependent antigens or TD antigens. Other antigens can elicit antibody production in the absence of T cells and are called thymus-independent antigens or TI antigens. There are two types of TI antigen: the TI-1 antigens, which have intrinsic B-cell activating activity, and the TI-2 antigens, which seem to activate B cells by having multiple identical epitopes that cross-link the B-cell receptor.

thymus-dependent lymphocyte

T cell and T lymphocyte are short designations for thymus-dependent lymphocyte, the lymphocyte population that fails to develop in the absence of a functioning thymus.

time-lapse video microscopy

One uses time-lapse video microscopy to examine processes in biology, that are anywhere from cell migration (fast) to a flower blossoming (slow).

tingible body macrophages

During the process of germinal center formation, cells called tingible body macrophages appear. These are phagocytic cells engulfing apoptotic B cells, which are produced in large numbers during the height of the germinal center response.

tissue dendritic cells

All dendritic cells arise from hematopoietic progenitors that migrate to various locations all over the body. Here, they are referred to as tissue dendritic cells

tissue grafts

Transplantation of organs or tissue grafts such as skin grafts is used medically to repair organ or tissue deficits.

tissue-specific autoimmune disease

Some autoimmune diseases attack particular tissues, such as the β cell in the islets of Langerhans in autoimmune diabetes mellitus; such diseases are called tissue-specific autoimmune disease.


The titer of an antiserum is a measure of its concentration of specific antibodies based on serial dilution to an end point, such as a certain level of color change in an ELISA assay.


see Toll-like receptors.

T lymphocytes

see T cells.


see lymphotoxin; tumor necrosis factor-α.

TNF receptor

There are several members of the TNF receptor (TNFR) family. Some lead to apoptosis of the cell on which they are expressed (TNFR-I, II, Fas), while others lead to activation (CD40, 4-1BB). All of them signal as trimeric proteins.


Tolerance is the failure to respond to an antigen; the immune system is said to be tolerant to self antigens. Tolerance to self antigens is an essential feature of the immune system; when tolerance is lost, the immune system can destroy self tissues, as happens in autoimmune disease.

Toll pathway

The Toll pathway is an ancient signaling pathway that activates the transcription factor NFκB by degrading its inhibitor IκB.

Toll-like receptors

All members of the Toll family of receptors so far discovered have been homologous to the original Toll in Drosophila. They have been named Toll-like receptors (TLR) followed by a number, as in Toll-like receptor 4 or TLR-4.


The palatine tonsils that lie on either side of the pharynx are large aggregates of lymphoid cells organized as part of the mucosal- or gut-associated immune system.

Toxic shock syndrome

Toxic shock syndrome is a systemic toxic reaction caused by the massive production of cytokines by CD4 T cells activated by the bacterial superantigen toxic shock syndrome toxin-1 (TSST-1), which is secreted by Staphylococcus aureus.


Inactivated toxins called toxoids are no longer toxic but retain their immunogenicity so that they can be used for immunization.


see regulatory T cells.


The family of proteins known as TNF receptor-associated factors, or TRAFs, consists of at least six members that bind to various TNF family receptors or TNFRs. They share a domain known as a TRAF domain, and have a crucial role as signal transducers between upstream members of the TNFR family and downstream transcription factors.


The active transport of molecules across epithelial cells is called trans-cytosis. Transcytosis of IgA molecules involves transport across intestinal epithelial cells in vesicles that originate on the basolateral surface and fuse with the apical surface in contact with the intestinal lumen.


The insertion of small pieces of DNA into cells is called transfection. If the DNA is expressed without integrating into host cell DNA, this is called a transient transfection; if the DNA integrates into host cell DNA, then it replicates whenever host cell DNA is replicated, producing a stable transfection.


Foreign genes can be placed in the mouse genome by transgenesis. This generates transgenic mice that are used to study the function of the inserted gene, or transgene, and the regulation of its expression.


Some cancers have chromosomal translocations, in which a piece of one chromosome is abnormally linked to another chromosome.


The grafting of organs or tissues from one individual to another is called transplantation. The transplanted organs or grafts can be rejected by the immune system unless the host is tolerant to the graft antigens or immunosuppressive drugs are used to prevent rejection.

Transporters associated with antigen processing

see TAP1 and TAP2.

tuberculin test

The tuberculin test is a clinical test in which a purified protein derivative (PPD) of Mycobacterium tuberculosis, the causative agent of tuberculosis, is injected subcutaneously. PPD elicits a delayed-type hypersensitivity reaction in individuals who have had tuberculosis or have been immunized against it.

Tuberculoid leprosy

see leprosy.

Tumor immunology

Tumor immunology is the study of host defenses against tumors, usually studied by tumor transplantation.

Tumor necrosis factor-α

Tumor necrosis factor-α (TNF) is a cytokine produced by macrophages and T cells that has multiple functions in the immune response. It is the defining member of the TNF family of cytokines. These cytokines function as cell-associated or secreted proteins that interact with receptors of the tumor necrosis factor receptor (TNFR) family, which in turn communicates with the interior of the cell via components known as TRAFs (tumor necrosis factor receptorassociated factors).

Tumor necrosis factor-β

Tumor necrosis factor-β (TNF): see lymphotoxin.

tumor-specific transplantation antigens

Tumors transplanted into syngeneic recipients can grow progressively or can be rejected through T-cell recognition of tumor-specific transplantation antigens (TSTA) or tumor rejection antigens. TSTA are peptides of mutant or overexpressed cellular proteins bound to MHC class I molecules on the tumor cell surface.

TUNEL assay

The TUNEL assay (TdT-dependent dUTP–biotin nick end labeling) identifies apoptotic cells in situ by the characteristic fragmentation of their DNA. Biotin-tagged dUTP added to the free 3′ ends of the DNA fragments by the enzyme TdT can be detected by immunohistochemical staining with enzyme-linked streptavidin.

two-dimensional gel electrophoresis,

In two-dimensional gel electrophoresis, proteins are separated by isoelectric focusing in one dimension, followed by SDS-PAGE on a slab gel at right-angles to the first dimension. This can separate and identify large numbers of distinct proteins.

type I hypersensitivity reactions

Hypersensitivity reactions are classified by mechanism: type I hypersensitivity reactions involve IgE antibody triggering of mast cells; type II hypersensitivity reactions involve IgG antibodies against cell surface or matrix antigens; type III hypersensitivity reactions involve antigen:antibody complexes; and type IV hypersensitivity reactions are T cell-mediated.

tyrosine kinase

A tyrosine kinase is an enzyme that specifically phosphorylates tyrosine residues in proteins. They are critical in T- and B-cell activation. The kinases that are critical for B-cell activation are Blk, Fyn, Lyn, and Syk. The tyrosine kinases that are critical for T-cell activation are called Lck, Fyn, and ZAP-70.



Urticaria is the technical term for hives, which are red, itchy skin welts usually brought on by an allergic reaction.


V domain

The variable region of the polypeptide chains of an immunoglobulin or T-cell receptor is composed of a single N-terminal V domain. Paired V domains form the antigen-binding sites of immunoglobulins and T-cell receptors.

V gene segments

The first 95 amino acids or so of immunoglobulin or T-cell receptor V domains are encoded in inherited V gene segments. There are multiple different V gene segments in the germline genome. To produce a complete exon encoding a V domain, one V gene segment must be rearranged to join up with a J or a rearranged DJ gene segment.


Vaccination is the deliberate induction of adaptive immunity to a pathogen by injecting a vaccine, a dead or attenuated (nonpathogenic) form of the pathogen.


The first effective vaccine was vaccinia, a cowpox virus that causes a limited infection in humans that leads to immunity to the human smallpox virus.


The valence of an antibody or antigen is the number of different molecules that it can combine with at one time.


The variability of a protein is a measure of the difference between the amino acid sequences of different variants of that protein. The most variable proteins known are antibodies and T-cell receptors.

Variability plot

see Wu and Kabat plot.

Variable gene segments

see V gene segments.

variable region

The variable region (V region) of an immunoglobulin or T-cell receptor is formed of the amino-terminal domains of its component polypeptide chains. These are called the variable domains (V domains) and are the most variable parts of the molecule. They contain the antigen-binding sites.

Vascular addressins

Vascular addressins are molecules on endothelial cells to which leukocyte adhesion molecules bind. They have a key role in selective homing of leukocytes to particular sites in the body.


see adaptor proteins.

V(D)J recombinase

The enzyme that joins the gene segments of B-cell and T-cell receptor genes is called the V(D)J recombinase. It is made up of several enzymes, but most important are the products of the recombinaseactivating genes RAG-1 and RAG-2 whose protein products RAG-1 and RAG-2 are expressed in developing lymphocytes and make up the only known lymphoid-specific components of the V(D)J recombinase.

V(D)J recombination

The process of V(D)J recombination is found exclusively in lymphocytes in vertebrates, and allows the recombination of different gene segments into sequences encoding complete protein chains of immunoglobulins and T-cell receptors.

very late antigens

The very late antigens (VLA) are members of the β1 family of integrins involved in cell–cell and cell–matrix interactions. Some VLAs are important in leukocyte and lymphocyte migration.


Vesicles are small membrane-bounded compartments within the cytosol.

viral envelope

Many viruses that are produced by mammalian cells are enclosed in a viral envelope of host cell membrane lipid and proteins bound to the viral core by viral envelope proteins.


Virions are complete virus particles, the form in which viruses spread from cell to cell or from one individual to another.


Viruses are pathogens composed of a nucleic acid genome enclosed in a protein coat. They can replicate only in a living cell, as they do not possess the metabolic machinery for independent life.


see pre-B-cell receptor.


Wegener’s granulomatosis

Antibodies against the neutrophil granule proteinase-3 are formed in Wegener’s granulomatosis, an autoimmune disease in which there is severe necrotizing vasculitis. The presence of anti-neutrophil cytoplasmic antigen, or ANCA, helps in the diagnosis of this disease.

Weibel–Palade bodies

Weibel–Palade bodies are granules within endothelial cells that contain P-selectin. Activation of the endothelial cell by mediators such as histamine and C5a leads to rapid translocation of P-selectin to the cell surface.

Western blotting

In Western blotting, a mixture of proteins is separated, usually by gel electrophoresis and transferred by blotting to a nitrocellulose membrane; labeled antibodies are then used as probes to detect specific proteins.

wheal-and-flare reaction

When small amounts of allergen are injected into the dermis of an allergic individual, a wheal-and-flare reaction is observed. This consists of a raised area of skin containing fluid and a spreading, red, itchy circular reaction.

white pulp

The discrete areas of lymphoid tissue in the spleen are known as the white pulp.

Wiskott–Aldrich syndrome

The Wiskott–Aldrich syndrome is characterized by defects in the cytoskeleton of cells due to a mutation in the protein WASP. Patients with this disease are highly susceptible to pyogenic bacteria.

Wu and Kabat plot

A Wu and Kabat plot, or variability plot, is generated from the amino acid sequences of related proteins by plotting the variability of the sequence against amino acid residue number. Variability is the number of different amino acids observed at a position divided by the frequency of the most common amino acid.



Animals of different species are xenogeneic.


The use of xenografts, organs from a different species, is being explored as a solution to the severe shortage of human organs for transplantation. The main problem with xenografting is the presence of natural antibodies against xenograft antigens; attempts are being made to modify these reactions by creating transgenic animals.


Mice with mutations in the btk gene have a deficiency in making antibodies, especially in primary responses. These mice are called xid, for X-linked immunodeficiency, the mouse equivalent of X-linked agammaglobulinemia, the human form of this disease.

X-linked agammaglobulinemia

X-linked agammaglobulinemia (XLA) is a genetic disorder in which B-cell development is arrested at the pre-B-cell stage and no mature B cells or antibodies are formed. The disease is due to a defect in the gene encoding the protein tyrosine kinase btk.

X-linked hyper IgM syndrome

X-linked hyper IgM syndrome is a disease in which little or no IgG, IgE, or IgA antibody is produced and even IgM responses are deficient, but serum IgM levels are normal to high. It is due to a defect in the gene encoding the CD40 ligand or CD154.

X-linked lymphoproliferative syndrome

X-linked lymphoproliferative syndrome is a rare immunodeficiency that results from mutations in a gene named SH2-domain containing gene 1A (SH2D1A). Boys with this deficiency typically develop overwhelming EBV infection during childhood, and sometimes lymphomas.

X-linked severe combined immunodeficiency

X-linked severe combined immunodeficiency (X-linked SCID) is a disease in which T-cell development fails at an early intrathymic stage and no production of mature T cells or T-cell dependent antibody occurs. It is due to a defect in a gene that encodes the γc chain that is a component of the receptors for several different cytokines.



The protein called ZAP-70 is found in T cells and is a relative of Syk in B cells. It contains two SH2 domains that, when bound to the phosphorylated ζ chain, leads to activation of kinase activity. The main cellular substrate of ZAP-70 is a large adaptor protein called LAT.

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Copyright © 2001, Garland Science.
Bookshelf ID: NBK10759


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