The aim of this project is to understand parameters associated with immunity against chlamydial infection and the response that occurs subsequent to immunization or infection. A murine-C. psittaci model will be employed for much of the proposed work. Special attention will be paid to distinguishing events that lead to protective immunity as opposed to immune-mediated latency. The latter phenomenon has been partially defined during the first 3 years of this project. Chlamydial latency will be studied in detail by completing the identification of the latency-inducing lymphokine, comparing in vitro induced latency with in vivo activated peritoneal cells and cryptically infected cells in culture. Mechanisms of latency will be investigated by establishing metabolic changes that accompany host cell activation and alterations of the metabolite pool that may lead to reversal of the active state. Comparisons will be made between gamma-interferon-like lymphokine activity and the known actions induced by interferons. Similarities and distinctions will be sought in lymphokine activity and antiviral mechanisms induced in interfron-treated cells. Immunity will be studied in comparative experiments involving active infections and immunizations using subcutaneous inoculation of viable chlamydiae, chlamydial cell envelope, and purified envelope components. Induction of IgM, IgG, and IgA will be measured by an indirect fluorescence test. Neutralizing antibody levels in serum and secretions will also be measured. Specific and non-specific blastogenesis, cytotoxic effector cell activity, antibody secretion via a plaque assay and lymphokine induction will be incorporated into all infection and immunization protocols. Evidence for immunosuppression will also be sought with the plaque assay to unrelated thymus dependent and independent antigens and also in the blastogenic assay. Results will help elucidate immune effector mechanisms against Chlamydia and distinguish protective from non-protective immunity. The long term goal of the investigation is to help establish if chlamydial vaccines are feasible, and if so, define the conditions that promote protective immunity.
Showing the most recent 10 out of 43 publications
