Accession Number : ADA186747

Title :   An Investigation of the Memory Response of the Local Immune System to Shigella Antigens.

Descriptive Note : Final rept. 1 Sep 80-15 Jun 87,

Corporate Author : MICHIGAN UNIV ANN ARBOR

Personal Author(s) : Keren, David F

PDF Url : ADA186747

Report Date : 30 Jun 1987

Pagination or Media Count : 47

Abstract : The chronically isolated ileal loop model has been established in rabbits as a probe for following the mucosal immune response to enteropathogens and their toxic products. We have studied several modes of immunization and several potential vaccine preparations with this model system. Our emphasis has been to use routes of antigen administration which would be feasible in human immunization attempts. With this model system, we have been able to follow the kinetics of the secretory immune response to Shigella flexneri. We have found that oral administration of nonpathogenic strains of Shigella flexneri are able to elicit a secretory IgA memory response in intestinal secretions. Parenteral immunization alone is ineffective in achieving this result. Heat-killed preparations of Shigella are also ineffective in eliciting a secretory IgA memory response. This likely reflects the poor uptake of this material by the gut-associated lymphoid tissues. Traditional parenteral adjuvants such as complete Freund's adjuvant are not effective in priming the mucosal immune response by an oral route. The secretory IgA created to Shiga toxin can prevent the toxic effects of this molecule in vitro. This suggests that the production of a secretory IgA memory response to Shigella flexneri and to Shiga toxin will be protective. We have begun to develop models to isolate lymphocytes and other functional cells such as Paneth cells from the gastrointestinal tract. By studying the location of B lymphoblasts committed to synthesizing IgA against enteropathogens, we will be able to develop more logical approaches for vaccine investigation.

Descriptors :   *ANTIGENS, *IMMUNIZATION, *SHIGELLA FLEXNERI, CELLS, HUMANS, IMMUNITY, ENTEROPATHOGENS, GASTROINTESTINAL SYSTEM, INTESTINES, LYMPHOCYTES, MODELS, IN VITRO ANALYSIS, MOLECULES, MUCOUS MEMBRANES, RESPONSE(BIOLOGY), PARENTERAL INFUSIONS, RABBITS, ANTIGENS, SHIGELLA, TOXICITY, VACCINES, INGESTION(PHYSIOLOGY), ORAL INTAKE, PREPARATION, SECRETION, IMMUNOGLOBULINS

Subject Categories : Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE