We have developed a model of one infectious process in which both arms of the immune system function and, in fact, operate in concert. In the first two years of this grant, we explored in detail the interactions of T cells and B. fragilis. Five areas of fundamental importance have emerged: 1) a soluble, small molecular weight lymphokine (ITF) of splenic phenotypic suppressor T cell origin confers antigenspecific immunity to abcesses, 2) protection in vivo and killing of B. fragilis in vitro require the presence of ITF and complement, 3) a circuit involving at least two suppressor T cells (by phenotype) is involved in immunity to abscesses, 4) an inducer T cell which is phenotypically Ly 1+2+ is necessary for the formation of abscesses, and 5) distinct determinants exist on the B. fragilis capsular polysaccharide for inducing cellular and humoral immunity. Based on these findings, we have evolved a hypothesis which will allow elucidation of a complete immune mechanism for a single infectious process, intraabdominal abscesses. The purpose of the current proposal is to test four components of the hypothetical scheme. These four specific aims include: 1) characterization of the antigenic determinant responsible for humoral and cellular immunity, 2) characterization of the cell types involved in immunity, 3) purification and characterization of the ITF produced by a T cell hybridoma which protects animals against abscesses and 4) in vitro and in vivo definition of the mechanisms of interaction between T cells and the complement system, an interaction which is necessary for protection against abscesses. These types of observations might appear to be unique to the anaerobe, B. fragilis, but hold the potential for a major expansion in the understanding of pathogenesis and host defense. Interactions of this sort have been described previously, but we know of no infectious processes which have been analyzed in this fashion. A number of important bacterial infections lack clear explanations of pathogenesis and immunity. Elucidation of the principles involved in our system may lead to an expanded level of understanding of other infectious diseases.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Bacteriology and Mycology Subcommittee 1 (BM)
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Brigham and Women's Hospital
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