The overall goal of this project is to utilize the Mycoplasma arthritidis mitogen (MAM), a model superantigen, (SAg) to define how these substances influence the immune systems of their natural hosts, how they contribute to disease by the organisms that produce them and finally how they interact with compromised hosts leading to immune- mediated or autoimmune disease. Using homogeneous native MAM and/or rMAM-his the investigators will: 1. Define the in vivo effect of MAM on the normal murine host in respect to comparison of different mouse strains; identification of responding cell types; determine the requirements for immunoenhancement vs. immunosuppression; examine the effect of chronic exposure of mice to MAM and neutralization of the in vivo effects of MAM by passive or active immunization. 2. Elucidate the role of MAM in disease induced by M. arthritidis in respect to understanding the mechanisms of lethal toxic shock syndrome and necrotizing fasciitis, acute and chronic arthritis including the role of cytokines specifically produced by MAM or constitutively as a result of host genes; protection against the pathological effects due to MAM by administration of a mutant MAM vaccine and determination of the role played by the potential synergistic effects of MAM and other biologically-active components of M. arthritidis. 3. Determine the mechanisms by which MAM influences the development of autoimmunity by use of collagen-induced arthritis of mice and experimental allergic encephalomyelitis. Specifically the investigator shall define the role played by SAg-induced cytokines and protection against disease using the MAM vaccines described earlier.
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