Investigations will continue into the basic mechanisms of host defenses to Salmonella infection in mice, as a model of human typhoid fever. Mice in the C3H lineage will be immunized with a vaccine strain of live, attenuated Salmonella which induces very high levels of protection against virulent challenge and concomitant marked immunosuppression. Although it is not known if T-cells can protect of suppress, macrophages have been shown to at least partially mediate both phenomena. To explore further the role of T-cells, cloned lines will be developed in vitro and tested for antigenic specificity and capacity to transfer Salmonella immunity. As macrophages have been shown to have protective and suppressive capacity, subsets of splenic and peritoneal macrophages from vaccinated and control mice will be purified and compared, to determine if these activities reside in the same or different populations. The cells mediating the immunosuppression, and the mechanisms involved, will be further investigated using an in vitro system of antibody formation. These studies should lead to a better understanding of the mechanisms of immunity to systemic Salmonella infection and provide a theoretical framework for development of an improved typhoid vaccine.
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