The overall objective of this work is to study the intestinal immune response of mice to the protozoan parasite Giardia muris.
One specific aim i s to determine whether antibodies directed against G. muris trophozoites are cytotoxic to these organisms in vitro. A related objective is to assess the viability of IgA-coated Giardia trophozoites harvested from the intestinal lumen of immunocompetent mice. In addition, the investigator plans to determine whether coating of G. muris trophozoites with anti- trophozoite antibody in vitro prevents these parasites from infecting the mouse intestine, and whether clearance of G. muris infection is accelerated by introducing anti-trophozoite antibody into the intestinal lumen of infected mice. A further objective is to identify the molecular weights, and the locations on the parasite, of trophozoite surface antigens against which intestinal IgA antibodies are directed in immunocompetent BALB/c mice. The long-term objective in this part of the work is to identify and purify trophozoite antigens that are targets for protective antibody in the mouse intestine. The cytotoxic and antigen- binding properties of anti-trophozoite antibodies in intestinal secretions of C3H/He mice will be compared with the corresponding properties of anti-trophozoite antibodies in BALB/c mouse intestinal secretions. Unlike BALB/c mice, C3H/He mice become chronically infected with G. muris. The investigator also plans to culture Peyer's patch B lymphocytes from Giardia- infected BALB/c mice, and to determine whether IgA antibody produced by these cells is directed against trophozoite antigens which are also recognized by IgA antibody in BALB/c mouse intestinal secretions. The question of whether helper/inducer T lymphocytes are necessary for the hyperplasia of IgA-bearing B lymphocytes, that occurs in mouse Peyer's patches before clearance of G. muris infection, will also be addressed. Because mice infected with G. muris constitute an animal model of human giardiasis, the work will provide insight into the mechanisms responsible for immunological clearance of Giardia lamblia from the human intestine.
