Intestinal mucosal immunosenescence in rats.
The elderly are characterized by systemic immunosenescence and high rates of morbidity and mortality associated with infectious diseases of the intestinal tract. Despite the consensus that the mucosal immune compartment is largely unaffected by aging, there are marked deficits in the intestinal mucosal immune responses of old animals and elderly humans. However, little is known about the mechanism(s) whereby aging disrupts intestinal immunity. Events in the generation of an intestinal immune response may be susceptible to the insults of aging. The first step involves the uptake of antigens by specialized follicular epithelial cells (M cells). There have been no studies on the efficacy of antigen uptake by M cells as a function of age. Little is known about the next step, i.e. antigen presentation by dendritic cells and subsequent isotype switching. The third event is the differentiation of putative immunolobulin A (IgA) plasma cells and their homing from the Peyer's patches (inductive site) to the lamina propria of the small intestine (effector site). Quantitative immunohistochemical and flow cytometry analyses suggest that the homing of IgA immunoblasts may be compromised in old rats and monkeys. Local antibody production/secretion by mature IgA plasma cells in the intestinal wall constitutes the fourth step. In vitro anti-cholera toxin IgA antibody secretion by intestinal lamina propria lymphocytes is equivalent in cells isolated from young adult and senescent rats. The final event in the mucosal immune response is the transport of IgA antibodies across the mucosal epithelial cells and their secretion onto the mucosal surface, i.e. receptor-mediated vesicular translocation of IgA by the intestinal epithelial cells. Binding assays did not detect age-associated declines in either the number or binding affinity of the polymeric immunoglobulin receptor expressed on rodent and monkey intestinal epithelial cells.
Schmucker
Douglas L
DL
Department of Anatomy, Veterans Affairs Medical Center, Cell Biology and Aging (151E), University of California, 4150 Clement Street, San Francisco, CA 94121, USA. coach@itsa.ucsf.edu
D000375:Aging / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D017578:Immunoglobulin Class Switching; D007413:Intestinal Mucosa / Q000276:immunology*; D051381:Rats
D000941:Antigens; D007070:Immunoglobulin A