In 1985, 28.3% of the 22.201 new cases of tuberculosis were in individuals over 65 years of age. The elderly are at triple jeopardy as regards risk of tuberculosis. First, they are the major reservoir for reactivation tuberculosis. Second. they are exposed to tuberculosis in the nursing home setting and frequently develop primary infection (3.5.5.0%/year). Third. they show increased risk of progression of recent and remote infection with M. tuberculosis to disease. The goal of this research is to explore the immunopathophysiology of aging as it pertains to, and may explain, the biologic predisposition of the elderly to tuberculosis. The hypothesis is that aging is associated with changes in the mononuclear phagocyte favoring hypoergy.
The Specific Aims are 1) to determine the relative contribution of disturbances in monocyte and lymphocyte function to the hyporesponsiveness of healthy elderly subjects to microbial antigens, including those to which they are intentionally boosted (tetanus toxoid) or recently exposed (tuberculin skin test conversion); 2) to examine, in healthy elderly subjects, monocyte properties key to the immune and inflammatory response: production and compartmentalization of interleukin.l and tumor necrosis factor. surface expression of Class II major histocompatibility complex determinants and intracellular growth of M. tuberculosis. 3) To study the compounding effects of aging and tuberculosis on the cellular immune response by contrasting disturbances in the immune response to microbial antigens and monocyte immunoregulatory function and properties in elderly patients with tuberculosis, to healthy elderly (and young) tuberculin skin test converters and younger patients with tuberculosis. These studies will be conducted in well-defined groups of young and elderly healthy subjects and patients with tuberculosis. Clinical and nutritional assessment will. be performed to characterize the state of health of elderly participants. This is a health-related project.
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