Studies will be performed to provide a better understanding of the biology and immunology of Toxoplasma gondii, the epidemiology, diagnosis and treatment of acute and chronic congenital and acquired toxoplasmosis, and the unique role of Toxoplasma in infection in the immunologically compromised patient. Purified preparations of antigens of the three stages of T. gondii will be isolated and characterized and used to study the humoral and cell-mediated immune response. Monoclonal antibodies will be formed against each of the three stages to use in studies on resistance and for detection and purification of antigens. The antigens and antibodies will be used to improve, develop, and evaluat methods for serologic diagnosis of all stages of the infection in animals and humans. We will study the nature of immune aggregates containing Toxoplasma antigens which are formed in humans with the infection and determine their role in the pathogenesis and diagnosis of the disease. The clinical manifestations, immune response, and methods of diagnosis in the immunocompromised patient will be studied as will genetic predisposition to various forms of acquired toxoplasmosis in normal humans. The immune response to Toxoplasma during pregnancy and the relationship of Toxoplasma to spontaneous abortion will be explored. The role of cell-mediated immunity and particularly the role of the macrophage in resistance to T. gondii will be studied and the biochemical mechanisms of inhibition and killing of the intracellular organism will be examined. An attempt will be made to define the relative roles of cell-mediated and humoral immunity in resistance to the organism and to define the mechanisms underlying the immunosuppression caused by Toxoplasma in laboratory animals and humans. Long-term follow-up of adverse sequelae in children born with asymptomatic congenital Toxoplasma infection will be performed and a series of studies will be executed to define newer therapeutic means for treatment of the congenital and acquired forms of toxoplasmosis. Because of their cross reactivity in serologic tests and in vivo, we will compare and contrast the antigen relationship between Toxoplasma and Hammondia and examine the cross resistance which exists in vivo against these organisms.
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