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Ageing Res Rev. 2015 Sep;23(Pt A):116-23. doi: 10.1016/j.arr.2015.01.005. Epub 2015 Feb 9.

As we age: Does slippage of quality control in the immune system lead to collateral damage?

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Max Planck Institute for Human Development, Lentzeallee 94, D-14195 Berlin, Germany.
Center for Medical Research, University of Tübingen, Waldhörnlestr. 22, D-72072 Tübingen, Germany. Electronic address:


The vertebrate adaptive immune system is remarkable for its possession of a very broad range of antigen receptors imbuing the system with exquisite specificity, in addition to the phagocytic and inflammatory cells of the innate system shared with invertebrates. This system requires strict control both at the level of the generation the cells carrying these receptors and at the level of their activation and effector function mediation in order to avoid autoimmunity and mitigate immune pathology. Thus, quality control checkpoints are built into the system at multiple nodes in the response, relying on clonal selection and regulatory networks to maximize pathogen-directed effects and minimize collateral tissue damage. However, these checkpoints are compromised with age, resulting in poorer immune control manifesting as tissue-damaging autoimmune and inflammatory phenomena which can cause widespread systemic disease, paradoxically compounding the problems associated with increased susceptibility to infectious disease and possibly cancer in the elderly. Better understanding the reasons for slippage of immune control will pave the way for developing rational strategies for interventions to maintain appropriate immunity while reducing immunopathology.


Aging; Autoimmunity; Immune deficiency; Immunosenescence; Thymic involution

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