CME review articleInnate and adaptive immunosenescence
Introduction
Immunosenescence is defined as changes in the immune system that develop with increasing age. Aging can affect both the innate and adaptive arms of the immune response. The clinical consequences of the aging immune system include susceptibility to infection, autoimmunity, and malignancy, which may increase hospitalizations and mortality of the aging population. Its study is important because people are living longer compared with years past and seeking to live those years in good health. The mechanisms of immunosenescence are not fully understood partly because of complexities of its research. Comorbid conditions may alter immune function studies and cytokine profiles. Therefore, several studies have used the SENIEUR protocol to screen patients to attempt to eliminate those who are unhealthy.1 Immunosenescence research is frequently performed in aged mice models that are easily manipulated and specifically targeted. This review focuses on the innate and adaptive age-associated immune changes and some of their clinical implications.
Section snippets
Macrophages
Blood monocytes and tissue macrophages are important cells of the innate immune system, phagocytosing microbes either through recognition of pathogen-associated molecular patterns or opsonins coating the microbe. Once engulfed in the phagosome, microbes are destroyed after fusion with a lysosome that contains enzymes and toxic substances, such as reactive oxygen intermediates and nitric oxide. Several studies suggest that macrophage/monocyte function decreases with aging through multiple
T Lymphocytes
There are several key changes in T-cell immunity that develop with increasing age, including decreased numbers of naive T cells, decreased antigen response and proliferation, increased memory cells, and alterations in apoptosis (Table 1). Furthermore, production of specific cytokine profiles may change with a shift from a TH1 response to a TH2-like response,33 although this is controversial.34 These events are most likely interconnected and result from several intrinsic processes, including
Consequences of Cellular Changes With Aging
The clinical implications of age-related dysregulation of the immune system include increased risk of infections, malignancy, autoimmune disorders, atherosclerosis, and neurodegenerative changes. These conditions likely result from alterations in several aspects of the immune system previously discussed rather than an isolated defect. A few of these topics will be discussed herein.
Interleukin 7
IL-7 plays several key roles in the immune system, including rearrangement of the TCRβ chain genes and lymphocyte survival at both preselection and postselection and thymic atrophy. Furthermore, memory cells express the IL-7 receptor. Several murine studies have shown that treatment with recombinant IL-7 in aged mice reverses thymic atrophy,67, 68 increases thymic output, and improves immune responses,69 whereas other studies have not reported similar results.70, 71 Administration of simian
Conclusions
The study of immunosenescence is critical as our population ages. Although not well characterized, aging most likely has several significant consequences on the immune function. Age-associated immune dysfunction in both the innate and adaptive sides may increase the risk of infections, malignancy, and autoimmune disease. Phagocytosis by PMNs and macrophages has been shown to be suppressed in both aged mouse models and humans. Furthermore, these cells may be more likely to undergo apoptosis in
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