The Cellular and Subcellular Bases of Immunosenescence

This chapter focuses on the cellular and intracellular basis for impaired immunologic activity, and the mucosal immune system provides evidence that not all lymphoid tissues are equally adversely affected by age.

Abstract

This chapter focuses on the cellular and intracellular basis for impaired immunologic activity. The activation of B and T cells, transit through the cell cycle, and differentiation present many points that might be age sensitive. Three possible mechanisms leading to, or contributing to, the decline in immune function will be considered: A shift in lymphocyte subset distribution with age, alterations in suppressor mechanisms, and changes in the maturation of B and T lymphocytes. The entry and transit of the cell cycle in T cells is thought to require delivery to the cell surface of several signals, triggering the sequential expression of several new proteins. This scheme involves the perturbation of the T cell receptor (TcR), activation of protein kinases, phosphorylation of target proteins, new mRNA synthesis, and protein synthesis, leading to the acquisition of receptors for interleukin 2 (IL-2) and increased expression of the receptor for transferring. It is not possible to identify a single age sensitive step in this sequence, but rather a series of deficiencies contribute to the decline in the competency of the aged lymphocytes to undergo normal activation. Thus, very early events, such as Ca2+ increases, accumulation of protooncogene transcripts, expression of activation markers, and synthesis of new proteins, are deficient in the aged. The mucosal immune system provides evidence that not all lymphoid tissues are equally adversely affected by age. Thus, while the response of lymphocytes derived from the peripheral lymphoid organs is diminished, the gut-associated lymphocytes from the same individual are often normally responsive.