This project's goal is to assess the relationship of immune T- and B-cell responses, measured in vitro, with manifestations of infection-associated morbidity and resistance to reinfection in human schistosomiasis haematobia. S. haematobium is a major cause of obstructive urinary tract pathology in Africa, and is associated with nutritional deficits, decreased work tolerance, anemia, and carcinoma of the bladder. The purpose of this project is to identify specific aspects of human immune response that enhance or modulate severity of disease; in light of the close association of infectious burden with the subsequent pathology, the research will also identify immune responses associated with resistance to infection. The experiments are designed to examine T-cell production interferon-gamma (IFNgamma), interleukin-2 (IL-2), IL-4 and IL-5 production to S. haematobium antigens (using immunoassay and ELISPOT techniques) as a function of patient age and infection status. Other ELISA and immunoblotting assays will measure antibody IgG, IgM and IgE antibody responses, including IgG subclass responses, to crude and defined parasite antigens. Experiments described under Specific Aim 1 will measure these responses in stratified subgroups of infected subjects identified in cross-sectional parasitological surveys of endemic Kenyan villages. The subgroups will include young children (8-11 yr.), older children (15-20), and adults to determine the association of immune parameters with age and intensity of chronic infection, and will evaluate the influence of curative therapy with praziquantel on the spectrum of T- and B-cell immune responses.
Specific Aim 2 will examine molecular mechanisms of T cell hyporesponsiveness associated with immunomodulation in chronic S. haematobium infection, while Specific Aim 3 will assess the association of characteristic Th1 and Th2 cell responses with resistance to reinfection following cure. Data from these studies of the regulation of immunopathology will provide important guidelines in designing strategies for disease control.
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