Immunology & Immunogenetics

Immunosenescence

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A decline in immune competence is well recognized in the elderly. Aged people show a decline in many aspects of protective immunity including a tendency to produce lower-affinity antibodies, a failure to generate long-lasting immunity to vaccination and a loss of delayed-type hypersensitivity to antigens previously encountered in life. Bacterial and viral diseases such as tuberculosis and herpes zoster (shingles), respectively, are found much more frequently in the elderly compared to young adults. Septicemia (infectious microbes in the bloodstream) is also more common in the elderly. Pneumonia is more prevalent and more often fatal and other viral and bacterial infections are more common in older people leading to an increase in morbidity and mortality. This decline in immune competence is not solely a result of a defective immune system, as it is also a result of changes in the endocrine and nervous systems, as well as nutritional and other factors including the general state of health of the older individual.

Malignancies are seen much more frequently in older people and while many of these may be related to inappropriate DNA translational events, a defective immune system may also be responsible since there is an association between immune deficiency and increased malignancy. Defects in all compartments of the immune system have been reported in the elderly. While studies are often contradictory, reliable data indicate that defects develop in T and B cell immunity as well as in the phagocytic component of immunity. Increased NK cell numbers and decreased γδ T cell function is also a feature of aging. IL-6 and IL-10 production by monocytes is increased with aging as well as the pro-inflammatory cytokines IL-1β and TNFα. MHC molecules are expressed at a lower density on a variety of cells and fewer T cells expressing CD28, important for T cell signaling, are found in the elderly. Antibody responses are usually of lower affinity and autoantibodies are found much more frequently. Hemopoiesis is impaired with fewer progenitor cells produced. Thymic involution is well established in the elderly with fewer T cells entering the vascular pool and hence secondary lymphoid organs. AICD and apoptosis are increased. Age-related changes in hormonal and neurotransmitter function may also have an impact on immune function and may determine morbidity, mortality, and longevity.