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This chapter addresses the following Geriatric Fellowship Curriculum Milestones: #8, #19

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LEARNING OBJECTIVES

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Learning Objectives

  • Recognize the relationship of immunosenescence with impaired vaccine responses and increased risk of infections such as zoster and influenza.

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Key Clinical Points

  1. 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. Responses to naïve antigens are often more impaired than memory responses.

  2. 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 young adults, a phenomenon termed “inflammaging,” and, though causal links have not yet been demonstrated, inflammaging is associated with cardiovascular events, Alzheimer disease, decreased muscle mass/strength, and mortality risk in cohorts of older adults.

  3. Cumulative immune changes render many vaccines less effective in seniors. Specific changes in vaccine formulation (eg, high-dose influenza vaccine, conjugated pneumococcal 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 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 in the bone marrow that give rise to all cell lineages of the immune system. Age-related immunologic alterations are manifested by 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 more often develop reactivation tuberculosis and varicella zoster virus (VZV) infection than young adults; age is also an independent risk factor for mortality and impaired functional outcome from sepsis. 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.

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EFFECTS OF AGING ON HEMATOPOIESIS

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Hematopoietic stem cells (HSC) in the bone marrow give rise to all blood ...

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