CME review article
Innate and adaptive immunosenescence

https://doi.org/10.1016/j.anai.2009.11.009Get rights and content

Objective

To review the effect of increasing age on the immune system and some of its clinical implications.

Data Sources

MEDLINE and PubMed searches were performed cross-referencing the keywords immunosenescence, aging, and immunity. Articles were reviewed for additional citations.

Study Selection

Articles were reviewed and selected based on relevance to subject matter.

Results

The study of immunosenescence is complex and not completely understood. Aging affects both the innate and adaptive arms of the immune response. With increased age, there may be a decrease in phagocytosis, alteration of cellular migration, changes in cell populations and numbers, and a decreased ability to produce specific antibodies. Clinically, these changes potentially increase morbidity and mortality in elderly individuals through an increased rate of infections, malignancy, and autoimmunity.

Conclusions

The process of aging is accompanied by diverse changes in immunity. Several therapeutic approaches are under investigation, including cytokine therapy, hormonal replacement, antioxidant supplementation, and caloric restriction, to attenuate or potentially reverse 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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    This educational activity is supported by an educational grant from GlaxoSmithKline.

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