Trypanosoma musculi infections are severe, often fatal, in aged mice, compared to young-adults, of all strains reflecting, primarily, deterioration of immune competence. The immunological elimination of T. musculi is an antibody (and C?)-facilitated function of Kupffer cells (KC) involving, particularly, Ab of the IgG2a isotype. How that process changes with age is unknown, but it is of considerable interest because a similar process is required for a variety of microbial infections that may be life- threatening in aged individuals. The research plan presented here is two- pronged. Much more information about the mechanism of immunological control of T. musculi infections in young animals is required. The plan is to devote considerable effort to that investigation initially (first 1/2 - 2 years) while re-establishing an aged mouse colony (lack of funds precluded maintenance of the previous colony). Studies will be devoted to: the roles of C3 fragments, C3 receptors and Fc receptors in promoting parasite elimination; identification of key antigens that elicit the synthesis of Abs that facilitate parasite elimination (Fac Ab); quantitative studies on the efficiency of Abs of different isotypes and specificities to serve as Fac Ab, utilizing especially a panel of 20-30 monoclonal antibodies (MAb) some of which are a hand; completing the development of 3 assays that are critical for quantitative comparisons of putative Fac Ab activities. As aged mice become available the emphasis will switch to: (i) evaluation of the course of appearance and quantities of Fac Ab during infections of young and aged mice; (ii) evaluation of the potentials of young and aged mice to generate Fac Ab; (iii) identification of key FAc Ab-inducing Ags and qualitative comparison of Fac Ab in young and aged mice with regard to Ag specificities and isotypes; (iv) analysis of the presence of substances that block T. Musculi elimination in the sera of young and aged, infected mice, identification of those substances and of methods to remove or neutralize them. The efficiency of KC of young and aged mice to remove parasites will be compared and methods for stimulating KC activity explored. Finally, we will identify the key epitopes that induce Fac Ab in mice, map their locations on the key parasite antigens and compare the Fac Ab elicited by those epitopes in young and aged mice.
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