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.

Immunopathology of parasitic diseases: a conceptual approach.

These studies would indicate tremendous variations in the clinical manifestations of parasitic disease, resulting from characteristics of the parasite, the host, and their interaction. They further suggest that the conceptual mechanistic model described in the introduction is highly applicable. Previous evidence to substantiate the validity of such a model in schistosomiasis, a variety of protozoan diseases, and leprosy has already been presented (Phillips and Fox, 1982). This report would appear to lend additional credence to the postulates and suggests that upon scrutiny, the model represents a reasonable explanation for a wide variety of clinical manifestations of a parasitic disease. In addition, it may provide a working hypothesis for the interpretation of the immunopathology found in other diseases such as filariasis. Figure 3 compares and contrasts schistosomiasis and filariasis within the context of this hypothesis. Immunopathology results from the relative balance of host-parasite immunogenic factors and modulatory specific and nonspecific factors. The resultant immunopathology results from a number of immunologic mechanisms, but for the sake of comparison can be placed in certain analogous groups. Clearly, although a number of experimental questions still exist, vis-à-vis these analogies, it would appear that they are reasonable comparisons. It is hoped that such a conceptual approach might provide a useful framework for an understanding of the spectrum of immunopathology resulting from parasitic disease. These concepts might possibly lead to the eventual control of immunopathology.