An Investigation of the Memory Response of the Local Immune System to Shigella Antigens
Midterm rept. 1 Aug 1987-2 Feb 1989,
MICHIGAN UNIV ANN ARBOR
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The secretory IgA response to shigella antigens has been investigated in rabbits and mice. These studies established a major route by which shigella are taken up for antigen processing by the gut-associated lymphoid tissues. The uptake by M cells overlying lymphoid follicles in the gut may serve as a double- edged sword. Whereas this is the initial step in processing of the shigella antigens to develop a mucosal immune response, it is also a portal of entry through which pathogenic shigella prefer to pass and where they can replicate creating the ulcerations characteristic of human dysentery. The cellular basis for the secretory IgA response is being investigated. Present studies have shown how lymphocytes from several sources of gut-associated lymphoid tissue can be used to determine when an animal has been effectively primed for a secretory IgA memory response against S. flexneri lipopolysaccharide. Future studies will dissect the role of T-cells in the development of this response. We have established that a secretory IgA response against Shiga toxin can be elicited in our Thirty-Vella loop model in rabbits. Further, by using the antibodies from these studies in both in vivo and in vitro evaluations, we found that the IgA anti-Shiga toxin can protect against the toxic effects of that molecule. Much of the secretory IgA immune response is directed against the A and B subunits of Shiga toxin when a crude preparation containing many other antigens is used to immunize rabbits intraloop. A mouse model for following the secretory IgA memory response to shigella antigens has been developed.
- Medicine and Medical Research