The major emphasis of work proposed in this project will continue to be directed toward an increased understanding of immune responses relevant to protection against chlamydial disease and defining how various elements of immunity to chlamydia contribute to protection, persistence, pathologic charges and recovery from infection. Much of the proposed work will involve studying of a murine model of protective immunity to chlamydia, recovery from chlamydial disease and persistence subsequent to either immunization or infection. Critical parameters related to cytokine mediated events also will be tested in vitro using human cell lines and, when appropriate, cytokines to evaluate if information obtained in the murine system applies to the human condition as well. The role of cytokines in mediating persistence, recovery from acute disease and cytolytic activity directed at infected host cells will be further evaluated. Renewed emphasis also will be placed on determining the extent of persistence subsequent to acute disease or induction of protective immunity following inoculation of viable chlamydial inocula. Cellular cloning of lymphocytes coupled with passive transfer experiments will provide evidence concerning the functional requirements for protective immunity and the chlamydial antigens that trigger induction of critical lymphocyte subpopulations. Innate defense will be compared between mouse strains that have recently been identified as differing in their susceptibility to chlamydia by approximately 100 million lethal inoculum doses. Finally, cross-protection studies will help elucidate the degree of immunity conferred between strains that differ to various extents in their antigenic composition.
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