Human Immunology

The incidence of infectious diseases, autoimmune syndromes, and cancers is increased in older adults and may be related to environmental and genetic factors. However, strong evidence also indicates that an overall dysregulation of the immune system may at least partially account for the increased incidence of these disorders in older adults.

Innate immunity. Changes in the innate immune response of older adults have received relatively little attention, and data thus far are inconclusive. Currently, the consensus is that NK activity does not dramatically change in older adults. However, lymphokine-activated killer-cell activity is decreased, at least to a limited extent, in older adults. Assessment of phagocytosis (process by which foreign substances (e.g., cells, bacteria, cell debris) are engulfed and destroyed) and cytokine production by cells of the innate response system has yielded inconsistent results, making it difficult to assess their role in the age-related decline in immune function. Clearly, additional controlled studies are necessary to define changes in innate immunity of older humans.

Adaptive immunity. Age-related changes in adaptive immunity have been studied extensively. Decreased antibody production after immunization or infection, reduced affinity of antibodies, and increased production of autoantibodies have been reported. However, these changes in B cell function cannot be explained by alterations in B cell numbers. The mechanism of age-related changes in B cell function has not yet been elucidated. Most evidence suggests that decreased B cell function probably reflects a decrease in help (i.e. cytokine production) from helper T cells, although some intrinsic changes in B cells have been identified.

There is a plethora of information regarding age-related changes in human T cell function. One of the earliest changes occurs in the thymus, the site of T cell maturation, which begins to involute at puberty. Involute refers to the atrophy of the thymus, resulting in a loss of collularity and a decrease in thymic function. However, the contribution of this change to decreased immune function of older adults is debatable, as involution occurs decades before decreased T cell responses are apparent. One of the most consistent findings is that proliferative responses of T cells to both nonspecific (mitogenic) and antigenic stimuli are decreased in elderly adults. A similar decrease is observed in both delayed-type hypersensitivity reactions and cytotoxic T cell activity.

To elucidate possible mechanisms for these age-related changes in T cell function, total cell number, distribution among various subsets, and cytokine production have been evaluated. Most, but not all, reports concur that the circulating number or percentage of T cells is not dramatically affected by age. However, investigators generally agree that a shift from a naïve to a memory phenotype is seen with advancing age in both CD4+ and CD8+ T subpopulations. This shift in phenotype could explain the reduced ability of older adults to produce immune responses to antigens that they have not encountered previously. The effects of age on T cell cytokine production have been variable and dependent on the cytokine measured and the stimulus (i.e., mitogen (substance that induces proliferation (cell division) of T and B cells, regardless of antigen specificity) or antigen) used for induction. The most consistent observation among human studies is that mitogen-induced interleukin (IL-2) production is decreased in elderly individuals. In contrast, IL-4, IL-6, IL-10 and interferon-γlevels after stimulation with either mitogen or antigen have been observed to increase, decrease, or not change with age. Collectively, however, current data clearly indicate that aging preferentially and consistently affects T cell function. This suggests that maintenance and/or restoration of T cell function are critical for sustaining immune function in older adults.