Chronic antigenic load and apoptosis in immunosenescence

The cells of the immune system undergo two different kinds of apoptotic processes: activation-induced cell death (AICD), peculiar to immune cells, and damage-induced cell death (DICD), a more generalized phenomenon in response to a variety of cellular insults, mainly oxidative metabolism by-products. AICD is geared towards the elimination of unnecessary lymphocytes following clonal expansion that results from antigenic stimulation, whereas DICD is particularly important for preventing the onset of neoplastic proliferation. We hypothesize that both oxidative stress and chronic antigenic load, which impinge heavily on the immune system, induce decreased lymphocyte susceptibility to DICD and a proinflammatory status leading to increased AICD. This subtle remodeling of AICD and DICD drives immunosenescence, contributing to the phenotypic and functional characteristics of the elderly immune system.