The regulation of resistance to Schistosoma mansoni by auto-anti-idiotypic immunity. II. Global qualitative and quantitative regulation.

These studies explore the suppression of resistance to schistosomiasis mansoni through interactions of autologous immune functions derived from an induced anti-idiotypic response. This anti-clonotypic response is induced by immunization with syngeneic L3T4+ receptor-bearing lymphoblasts and for the sake of description is termed "auto-anti-idiotypic". It is antigenically restricted and cannot be induced by allogeneic cells. Anti-idiotypic immunization profoundly suppressed the development of protective immunity after exposure to irradiated cercariae and altered a wide variety of functional humoral and cellular immune responses to the parasite. In addition to quantitative suppressive effects, the anti-idiotypic network also regulated qualitative aspects of the immune response by increasing the heterogeneity and reducing the functional binding avidity of antibody for Ag. These effects also were reflected in analogous alterations in cellular reactivity, using the criteria of the Ag mediated blast transformation and delayed type hypersensitivity. Thus idiotypic regulation can mold the specificity and sensitivity of the immune response to Schistosoma mansoni by affecting quantitative and qualitative responses. Manipulation of idiotypic recognition provides an approach to optimize the expression of protective resistance to schistosomiasis.

The regulation of resistance to Schistosoma mansoni by auto-anti-idiotypic immunity.

These studies explore auto-anti-idiotypic mechanisms as potential regulators of the protective immune response against Schistosoma mansoni. Anti-idiotypic responses were stimulated by immunization of mice with lymphoblasts, bearing specific idiotypic receptors. These receptors were produced in vitro by stimulation of Ag-reactive T cells by soluble cercarial immunogen, keyhole limpet hemocyanin, or Con A. The animals were then exposed to irradiated cercariae, keyhole limpet hemocyanin, or SRBC. The results indicate that the soluble cercarial immunogen lymphoblast recipient mice demonstrated reduction in a number of parameters of their immune response to schistosome Ag, including resistance to challenge by parasites. These changes were immunologically specific. Anti-idiotypic antibodies and anti-clonotypic T cell reactivity was demonstrated in the lymphoblast immunized mice. The suppression of reactivity in LBM was mediated by Lyt-1-, L3T-4-, and Lyt-2+ lymphocytes. These studies suggest that idiotypically dependent pathways might be important for the regulation of resistance to schistosomiasis.

Epitopic and paratopically directed anti-idiotypic factors in the regulation of resistance to murine schistosomiasis mansoni.

In this study we investigated aspects of targets and regulatory mechanisms of immunologically mediated resistance to schistosomiasis. The interactions of antigen, monoclonal antibodies (MAb), and anti-idiotypic antibodies were studied by using competitive inhibition ELISA, radioimmunoprecipitation, and direct-binding ELISA techniques. MAb, either protective or nonprotective against challenge with Schistosoma mansoni, recognize either discrete or shared epitopes. MAb that recognize the same specific epitope may or may not express the ability to adoptively transfer resistance to syngeneic recipients. These results suggest that the functional as well as the epitopic specificity must be considered in an evaluation of protective mechanisms. The antibodies also can be characterized by both unique and cross-reacting idiotypic determinants. In addition, a relationship between antigen and anti-idiotypic antibody activity has been demonstrated. The immunologic analogy between antigenic epitopes and anti-idiotypic antibodies has been demonstrated by the ability of these two moieties to reciprocally inhibit the recognition of paratope-associated idiotypes, expressed by the protective MAb. This anti-idiotypic activity can be demonstrated in serum of infected animals. In this study we have identified two specific epitopes related to protection, and we illustrate here the steric relationship between antigen and anti-idiotypic antibody. The presence of idiotypically directed regulatory pathways within actively infected animals suggests that the immune response can be differentially regulated at the clonal level.