The rapid expansion of the aged population, the increased incidence of gastrointestinal infections and diseases ad the age-related decline in immunocompetence demonstrated the need for a comprehensive, quantitative analysis of the mucosal immune system as a function of age. In spite of the considerable research on the effects of aging on immunocompetence, the mucosal immune system has not been accorded significant attention. Furthermore, recent evidence for our laboratory suggests that an age- dependent decline in immunoglobulin A producing cells in the lamina propria of the intestine, and a concomitant decline in nonimmune tissue secretion dimeric immunoglobulin A (digA), e.g. a decline in the levels of hepatobiliary secretion of digA due to loss of receptors may affect mucosal immunity. While current dogma states that aging affects cell-mediated immune responses more markedly than the humoral response, these and other data suggest that intrinsic alteration in B-lymphocyte or non-lymphoid elements may also play a role in this immunodeficiency. The overall aim of the proposed project is to understand the role of receptor-mediated IgA transport in the intestinal immune response and how mucosal immunocompetence is affected by aging. In order to achieve this goal, we propose to examine the effect of animal age on the synthesis and subcellular processing of the hepatic Iga receptor, secretory component, and the role of secretory component-mediated transport of immunoglobulin A in the intestinal immune response in the aging Fischer 344 rat. In addition, mechanisms by which the intestinal immune response to a specific antigen e.g. cholera toxin, results in homing of specific anti-cholera toxin producing cells to liver and the intestinal tract will be examined. The proposed studies will provide important information concerning 1) the intrinsic role of the IgA receptor in the transport of Iga in the intestinal immune response, 2) the role of tissue specific homing of primed lymphocytes to site for secretion of IgA and 3) the effect of aging on these functions. In addition, these studies will also increase our current knowledge of the subcellular mechanisms involved in the processing of molecules internalized via receptor-mediated endocytosis and the mechanisms by which cells respond in the mucosal immune system.
| Daniels, C K; Zhang, L; Musser, B et al. (1994) A solid-phase radioimmunoassay for cyclic AMP. J Pharmacol Toxicol Methods 31:41-6 |
| Daniels, C K; Perez, P; Schmucker, D L (1993) Alterations in CD8+ cell distribution in gut-associated lymphoid tissues (GALT) of the aging Fischer 344 rat: a correlated immunohistochemical and flow cytometric analysis. Exp Gerontol 28:549-55 |
| Gregoire, C D; Zhang, L; Daniels, C K (1992) Expression of the polymeric immunoglobulin receptor by cultured aged rat hepatocytes. Gastroenterology 103:296-301 |
