This Program Project for a Tropical Disease Research Unit proposes study of four parasitic diseases that are endemic in the developing world. Two, leishmaniasis and South American trypanosomiasis, are caused by protoxoa, and filariasis and schistosomiasis are caused by helminths. The present proposal takes an immunologic approach to study of these diseases. Emphasis is placed on delineating and isolating the antigens which induced protective immunity using monoclonal antibodies produced by lymphocyte hybrids. These antigens will be used to develop specific diagnostic tests and eventually vaccines. Studies on the mechanism of protective immunity should aid in the production of the latter, and those on immunpathology should lead to measures to prevent the consequences of infection. In the leishmania project, an emphasis is placed on delineating species specific antigens from organisms prevalent in the New World and on the interaction of different species of leishmania with activated human macrophages. In the filariasis project, in addition to the studies on stage specific antigens and mechanism of immunity and immunopathology, there are studies on the interaction of worms with coagulation factors and platelets. In the trypanosomiasis project, the mechanism of cell-mediated immunity involved in killing blood stream forms of T. cruzi is stressed. In the schistosomiasis projects, emphasis is placed on studying changes on the surface of the schistosomula that lead to immune evasion and those that are caused by immune attack; studies are also proposed on the mechanism of eosinophil-mediated killing of the larvae, and on isolating relevant target antigens. Cores on electron microscopy and morphology, on lymphocyte hybridomas, and on maintaining the life cycles are included.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI022794-03
Application #
3091682
Study Section
Microbiology and Infectious Diseases Research Committee (MID)
Project Start
1985-02-01
Project End
1990-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Harn, D A; Gu, W; Oligino, L D et al. (1992) A protective monoclonal antibody specifically recognizes and alters the catalytic activity of schistosome triose-phosphate isomerase. J Immunol 148:562-7
Shoemaker, C; Gross, A; Gebremichael, A et al. (1992) cDNA cloning and functional expression of the Schistosoma mansoni protective antigen triose-phosphate isomerase. Proc Natl Acad Sci U S A 89:1842-6
Kahl, L P; Byram, J E; David, J R et al. (1991) Leishmania (Viannia) braziliensis: comparative pathology of golden hamsters infected with isolates from cutaneous and mucosal lesions of patients residing in Tres Bracos, Bahia, Brazil. Am J Trop Med Hyg 44:218-32
Caulfield, J P; Hein, A; Rothenberg, M E et al. (1990) A morphometric study of normodense and hypodense human eosinophils that are derived in vivo and in vitro. Am J Pathol 137:27-41
Kahl, L P; Byram, J E; David, J R (1990) Leishmania (Viannia) braziliensis isolated from cutaneous and mucosal lesions of patients residing in Tres Bracos, Bahia, Brazil differ in virulence for the golden hamster. Trans R Soc Trop Med Hyg 84:783-4
Silberstein, D S; David, J R; Harn, D A (1990) The ability of mouse monoclonal antibodies to direct the cytotoxic function of cytokine-activated human eosinophils. Hybridoma 9:237-42
Silberstein, D S; Ali, M H; Baker, S L et al. (1989) Human eosinophil cytotoxicity-enhancing factor. Purification, physical characteristics, and partial amino acid sequence of an active polypeptide. J Immunol 143:979-83
Widmer, G; Comeau, A M; Furlong, D B et al. (1989) Characterization of a RNA virus from the parasite Leishmania. Proc Natl Acad Sci U S A 86:5979-82
Titus, R G; Sherry, B; Cerami, A (1989) Tumor necrosis factor plays a protective role in experimental murine cutaneous leishmaniasis. J Exp Med 170:2097-104
Chiang, C P; Caulfield, J P (1989) The binding of human low-density lipoproteins to the surface of schistosomula of Schistosoma mansoni is inhibited by polyanions and reduces the binding of anti-schistosomal antibodies. Am J Pathol 134:1007-18

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