The primary objectives of the proposed research is to continue to define and characterize the molecular mechanisms underlying genetically determined resistance and susceptibility in snails, Biomphalaria glabrata, to infection by larvae of the human blood fluke, Schistosoma mansoni. Genetically defined susceptible (PR albino) and resistant (10-R2, 13-16-R1, 243432) strains of B. glabrata will be employed in comparative immunological and biochemical studies designed to provide an in-depth analysis of the three interacting components involved in the immune association between S. mansoni and its snail host: the circulating hemocyte, soluble hemolymph factors, and the tegumental surface of schistosome larvae. Specifically, monoclonal antibody probe methods, in conjunction with in vitro cultivation, biochemical (e.g., HPLC), and microinjection techniques, will be employed to (1) identify and characterize molecularly distinct hemocyte populations and determine their impact on parasite immune interactions, (2) analyze the soluble constituents comprising the hemolymph of resistant snails and assess the role of isolated serum factors in mediating schistosome recognition and/or host hemocyte activation, (3) investigate the antigenic composition of the larval schistosome surface with emphasis on the functional role of primary sporocyst tegumental components in determining the degree of immune compatibility exhibited by the different snail host strains, and (4) establish an in vivo model for assessing the relative importance of cellular and humoral defense elements in determining natural or induced parasite resistance within the intact host. The long-term goal of this research is to establish a firm base from which the biochemical parameters regulating immune interactions between various invertebrate vectors and their human-infecting parasites can be precisely defined and eventually applied to vector control methodologies.