These studies are designed to investigate the role of idiotypic regulation in the development and expression of resistance to schistosomiasis. Two strategic or long term goals are sought: 1. The elucidation of possible alternative modes of immunization which may "improve on nature"; 2. The establishment of possible methods to monitor the development of clinical resistance without the requirement of invasive challenge/perfusion procedures. To accomplish these strategic goals, animals will first be infected with S. mansoni cercariae and sacrificed at serial intervals. They will be assessed, for the presence of factors such as antibody or cells with the ability to modulate, at the idiotypic level, specific anti-schistosomal responses related to immunity. Once these constituents are demonstrated, they will be precisely defined both phenotypically and functionally to more fully assess the constituents and establish interactions in an idiotypic regulatory network. In vivo and in vitro assays will be correlated to the resistance status of the donor, determined by challenge. Animals will then be exposed to irradiated cercariae to induce active immunity and thus enable measurement of the sequential development of the participants in the immunoregulatory network. Following the establishment of the components and optimal assays, isolated constituents of a protective network will be specifically utilized to enhance or suppress the development of protective immunity. These studies will demonstrate the biological relevance of the network to resistance. The optimal mode of monitoring the interactions of that network may provide a practical method to ascertain the status of in vivo immunity. Ultimately, the network will be perturbed, in a directed manner, to optimize protective immunity. The various defined idiotypic components-both cellular and humoral-will be selectively utilized alone or in combination. Thus these studies represent an important new approach to the induction and monitoring of resistance to schistosomiasis.