Schistosoma mansoni: Immune response to normal and irradiated cercariae or soluble stage-specific surface immunogens

Abstract

The effects of a variety of exposure regimens were assessed for their ability to induce optimal, immunologically mediated resistance against subsequent homologous reinfection by Schistosoma mansoni The mechanisms whereby natural infection or artificial immunization lead to the development of optimal protective immunity against reinfection by homologous S. mansoni were investigated. Animals, exposed to normal or irradiated cercariae, demonstrated strong resistance to reinfection by S. mansoni. They also developed a population of T-lymphocytes, which could adoptively transfer resistance to in vivo and specifically interact with immunogen in vitro. Subsequently these animals produced antibody capable of adoptively transferring resistance and possessing a variety of antischistosomal activities. Animals exposed to soluble cercarial immunogen demonstrated moderate resistance upon re-exposure. They failed to produce a significant population of sensitized T-lymphocytes. Moreover, although these animals produced unimpaired levels of cytotoxic, complement-fixing, and hemagglutinating antibody, their sera did not adoptively transfer resistance. Adult worm and egg immunogens were even less effective than cercarial immunogen in stimulating resistance. In addition, these membrane-derived immunogens directly stimulated B-lymphocyte blastogenesis in vitro. These studies suggest that the optimal production of protective immunity requires the stimulation of T-dependent mechanisms by stage-specific immunogens. This stimulation is produced more effectively by the use of immunogens which may be working through relatively T-independent mechanisms. The implication of these studies would suggest that the optimal development of protective immunity will require some form of immunologic process which mirrors closely the natural disease process. The sequential stimulation of relevant T- and B-dependent mechanisms by appropriate stage-specific immunogens appears to be a prerequisite for the development of optimal protective immunity. Thus, programs utilizing immunizations through exposure to irradiated cercariae or heterologous organisms which are non-pathogenic in man would appear promising, since these forms of exposure would efficiently stimulate protective immunity.