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Learning Objectives
Recognize the relationship of immunosenescence with impaired vaccine responses and increased risk of infections such as zoster, influenza, and SARS-CoV-2.
Understand the age related changes in the immune system that lead to “inflammaging.”
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Key Clinical Points
Immunosenescence—the cumulative effect of aging on immune function—affects all cell types and many molecular pathways at all levels of the immune response. The resulting general phenotype is one of low-level inflammation at baseline, but impaired innate and adaptive immune responses to an acute stimulus. Reponses to naïve antigens are often more impaired than memory responses.
Increased levels of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), acute phase reactants such as C-reactive protein (CRP), and clotting factors are found in the plasma of older adults, compared to younger adults, a phenomenon called “inflammaging,” and thought causal links have not yet been demonstrated, is associated with cardiovascular events, Alzheimer disease, decreased muscle mass/strength, and mortality risk in cohorts of older adults.
Cumulative immune changes render many vaccines less effective in seniors. Specific changes in vaccine formulation (eg, high-dose influenza vaccine, conjugated pneumococcal vaccine, recombinant Zoster vaccine) attempt to address this concern, and clinical efficacy trials demonstrate benefit versus standard vaccines in some (eg, high-dose influenza).
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OVERVIEW OF IMMUNOSENESCENCE
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Immunosenescence refers to the changes in the immune system that occur with aging. These changes affect virtually all cell lineages of the immune system, and result in alterations in diverse innate immune responses mediating the earliest interactions of the immune system with pathogens or vaccines, as well as slower onset, highly specific adaptive immune responses in B cells and T cells. Indeed, these changes extend to hematopoietic stem cells (HSC) in the bone marrow that give rise to all cell lineages of the immune system. These immunological alterations are manifested in changes in cellular signal transduction or function that may arise from intrinsic mechanisms with a genetic component, but also reflect the complex interactions of the aged immune system with factors such as chronic or repetitive infection (such as with herpesvirus family reactivation or HIV), hormonal changes, and endogenous cellular damage as a potential result of chronic medical conditions. Immunosenescence has profound clinical consequences in older adults, who are at increased risk for morbidity and mortality from infectious diseases. For example, older adults are at increased risk for the development of reactivation tuberculosis and varicella zoster virus (VZV) infection; age is also an independent risk factor for mortality and impaired functional outcome from sepsis and infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19. Immune system aging also contributes to impaired responses to vaccines against influenza and other pathogens. The protean manifestations of immunosenescence provide insights into clinically important problems that disproportionately affect older adults and potential interventions to improve immunologic responses. Here, we provide an overview of aging of the human immune system.