From HIV to influenza, the battle between infectious agents and the immune system is at the heart of disease. Knowledge of how and why parasites vary to escape recognition by the immune system is central to vaccine design, the control of epidemics, and our fundamental understanding of parasite ecology and evolution. As the first comprehensive synthesis of parasite variation at the molecular, population, and evolutionary levels, this book is essential reading for students and researchers throughout biology and biomedicine.

The author uses an evolutionary perspective to meld the terms and findings of molecular biology, immunology, pathogen biology, and population dynamics. This multidisciplinary approach offers newcomers a readable introduction while giving specialists an invaluable guide to allied subjects. Every aspect of the immune response is presented in the functional context of parasite recognition and defense—an emphasis that gives structure to a tremendous amount of data and brings into sharp focus the great complexity of immunology. The problems that end each chapter set the challenge for future research, and the text includes extensive discussion of HIV, influenza, foot-and-mouth disease, and many other pathogens.

This is the only book that treats in an integrated way all factors affecting variation in infectious disease. It is a superb teaching tool and a rich source of ideas for new and experienced researchers. For molecular biologists, immunologists, and evolutionary biologists, this book provides new insight into infectious agents, immunity, and the evolution of infectious disease.

Contents

• Acknowledgments
• 1. Introduction
• I. Background
  • 2. Vertebrate Immunity
    • 2.1 Nonspecific Immunity
    • 2.2 Specific Immunity: Antigens and Epitopes
    • 2.3 B Cells and Antibodies
    • 2.4 T Cells and MHC
    • 2.5 Summary
  • 3. Benefits of Antigenic Variation
    • 3.1 Extend Length of Infection
    • 3.2 Infect Hosts with Prior Exposure
    • 3.3 Infect Hosts with Genetically Variable Resistance
    • 3.4 Vary Attachment Characters
    • 3.5 Antigenic Interference
    • 3.6 Problems for Future Research
• II. Molecular Processes
  • 4. Specificity and Cross-Reactivity
    • 4.1 Antigens and Antibody Epitopes
    • 4.2 Antibody Paratopes
    • 4.3 Antibody Affinity Maturation
    • 4.4 Natural Antibodies—Low-Affinity Binding to Diverse Antigens
    • 4.5 Affinity versus Specificity
    • 4.6 Cross-Reaction of Polyclonal Antibodies to Divergent Antigens
    • 4.7 T Cell Epitopes
    • 4.8 Every Host Differs
    • 4.9 Problems for Future Research
  • 5. Generative Mechanisms
    • 5.1 Mutation and Hypermutation
    • 5.2 Stochastic Switching between Archival Copies
    • 5.3 New Variants by Intragenomic Recombination
    • 5.4 Mixing between Genomes
    • 5.5 Problems for Future Research
• III. Individual Interactions
  • 6. Immunodominance within Hosts
    • 6.1 Antibody Immunodominance
    • 6.2 CTL Immunodominance
    • 6.3 Sequence of Exposure to Antigens: Original Antigenic Sin
    • 6.4 Problems for Future Research
  • 7. Parasite Escape within Hosts
    • 7.1 Natural Selection of Antigenic Variants
    • 7.2 Pathogen Manipulation of Host Immune Dynamics
    • 7.3 Sequence of Variants in Active Switching from Archives
    • 7.4 Ecological Coexistence of Variants within a Host
    • 7.5 Problems for Future Research
• IV. Population Consequences
  • 8. Genetic Variability of Hosts
    • 8.1 Polymorphisms in Specificity
    • 8.2 Polymorphisms in Immune Regulation
    • 8.3 Problems for Future Research
  • 9. Immunological Variability of Hosts
    • 9.1 Immunological Memory
    • 9.2 Kinds of Parasites
    • 9.3 Immunodominance of Memory
    • 9.4 Cross-Reactivity and Interference
    • 9.5 Distribution of Immune Profiles among Hosts
    • 9.6 Problems for Future Research
  • 10. Genetic Structure of Parasite Populations
    • 10.1 Kinds of Genetic Structure
    • 10.2 Pattern and Process
    • 10.3 Genome-wide Linkage Disequilibrium
    • 10.4 Antigenic Linkage Disequilibrium
    • 10.5 Population Structure: Hosts as Islands
    • 10.6 Problems for Future Research
• V. Studying Evolution
  • 11. Classifications by Antigenicity and Phylogeny
    • 11.1 Immunological Measures of Antigenicity
    • 11.2 Phylogeny
    • 11.3 Hypothetical Relations between Immunology and Phylogeny
    • 11.4 Immunology Matches Phylogeny over Long Genetic Distances
    • 11.5 Immunology-Phylogeny Mismatch with Radiations into New Hosts
    • 11.6 Short-Term Phylogenetic Diversification Driven by Immunological Selection
    • 11.7 Discordant Patterns of Phylogeny and Antigenicity Created by Within-Host Immune Pressure
    • 11.8 Problems for Future Research
  • 12. Experimental Evolution: Foot-and-Mouth Disease Virus
    • 12.1 Overview of Antigenicity and Structure
    • 12.2 Antibody Escape Mutants
    • 12.3 Cell Binding and Tropism
    • 12.4 Fitness Consequences of Substitutions
    • 12.5 Problems for Future Research
  • 13. Experimental Evolution: Influenza
    • 13.1 Overview of Antigenicity and Structure
    • 13.2 Antibody Escape Mutants
    • 13.3 Cell Binding and Tropism
    • 13.4 Fitness Consequences of Substitutions
    • 13.5 Experimental Evolution of Other Pathogens
    • 13.6 Problems for Future Research
  • 14. Experimental Evolution: CTL Escape
    • 14.1 Cleavage and Transport of Peptides
    • 14.2 MHC Binding
    • 14.3 TCR Binding
    • 14.4 Functional Consequences of Escape
    • 14.5 Kinetics of Escape
    • 14.6 Problems for Future Research
  • 15. Measuring Selection with Population Samples
    • 15.1 Kinds of Natural Selection
    • 15.2 Positive Selection to Avoid Host Recognition
    • 15.3 Phylogenetic Analysis of Nucleotide Substitutions
    • 15.4 Predicting Evolution
    • 15.5 Problems for Future Research
• VI. Discussion
  • 16. Recap of Some Interesting Problems
    • 16.1 Population-Level Explanation for Low Molecular Variability
    • 16.2 Molecular-Level Explanation for Population Dynamics
    • 16.3 Binding Kinetics and the Dynamics of Immunodominance
    • 16.4 Diversity and Regulation of Archival Repertoires
    • 16.5 Final Note
• References