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Immunological Aging
Citation:
DEWITT, J. AND R. W. LUEBKE. Immunological Aging. 2nd, Chapter 5, D. A. LAWRENCE (ed.), Comprehensive Toxicology. Elsevier Ltd, Oxford, Uk, 5:455-465, (2010).
Impact/Purpose:
Mild to moderate immunosuppression is associated with an increased risk of infection with common pathogens in human adults, and the type and frequency of infection can be associated with the severity of suppression. It is not unreasonable to consider that the elderly may be at greater risk of xenobiotic-induced immunotoxicity than young, healthy adults. Regulatory agencies have acknowledged that the elderly constitute a subpopulation that may be at greater risk for adverse effects following exposure to environmentat chemicals (e.g., US EPA, 2005, World Health Organization/IPCS, 1993), although age as a risk factor has typically only been considered when setting exposure levels for the very young. Age as a risk factor for increased immunotoxicity, and consideration of age when conducting hazard identification for immunotoxicity risk assessment, has not been evaluated systematically. This constitutes a significant data gap in our understanding of the aged population as a susceptible subgroup, particularly as the average lifespan increases and members of the mid-twentieth century population boom enter their 60s and 70s. Nevertheless, the elderly are more susceptible to immediate adverse effects of inhaled fine particles and experience more severe adverse effects of chemical exposure from altered toxicokinetics or control of oxidative damage. This chapter describes the effects of natural aging on the immune system at the molecular, cellular and organism level, and the impact that immunological aging and chemical exposure have on disease. There is an extensive body of literature dedicated to immunosenescence and the underlying mechanisms of immune system dysregulation, and a complete review is beyond the scope of this chapter. Examples were selected to illustrate changes that accompany the aging process, effects on the immune system, specific defects at the molecular and cellular levels, and the consequences that these alterations have on system health and disease.
Description:
Immunosenescence is associated with an increased incidence and severity of infections with common pathogens, neoplastic disease and autoimmunity. In general, aging is associated with a decline in function at the cellular level, rather than cell loss, although thymic atrophy and the resulting decrease in the supply of naïve T cells has a significant impact on the ability to respond to novel antigens, including vaccines. Age-related changes in physical and physiological defense mechanisms compound the effects of reduced immune function by failing to limit pathogen entry or accumulation of infectious agents, increasing the risk of infection and infection-related damage. It remains to be determined whether acute or chronic exposure to xenobiotics contributes to disease incidence in aged humans, although studies in stressed populations of older humans provide clear evidence that extrinsic factors reduce response to vaccination. Current risk assessment practices acknowledge the elderly as a potentially sensitive population, and the WHO/IPCS Criteria document 144, (WHO, 1993) specifically discusses age- but not chemical-related changes in immune function. Very few studies, however, have evaluated whether immunosenescence reduces the effective dose, or prolongs the effects, of known immunotoxicants on immune system endpoints. Only two studies were identified that evaluated innate and adaptive responses to challenge infections or immunization, using techniques and methods typically employed by immunotoxicologists. This significant data gap hinders the ability of risk assessors to make science-based decisions about the risks faced by the growing elderly population, and to make informed judgments when setting exposure levels.