The aging immune system: Dysregulation, compensatory mechanisms, and prospects for intervention

Abstract

Despite its dynamic organization and self-renewal capacity, with large numbers of its cellular components continually turning over and being replaced, the immune system in older people is different from that of the young. Much but not all of this is reflected in different distributions of cells of the adaptive immune system, with innate immunity showing less marked age effects. In humans, most available data pertain to peripheral blood with relatively little known about differences in other organs. Differences at the level of hematopoiesis contribute to these age effects, as does thymic involution in the case of T cells. The main drivers of the changes in adaptive immunity are pathogen exposure throughout life with the accumulation of T and B cells imbuing memory to previously encountered agents or maintaining immunosurveillance against persistent agents, and the reciprocal decrease of naïve cells which have not been exposed to their cognate antigens. True “senescence” in the pathological sense is hard to determine in human immunity, and may only occur very late in life when clonal exhaustion and attrition contribute to failing memory immune responses or contraction of the naïve cell repertoire results in the lack of appropriate receptors to respond to certain neoantigens.