This proposal is a competitive renewal to continue 12 years of work on Schistosoma mansoni. There are three major areas of interest each of which has three subprojects. The first area centers on the cercarial glycocalyx. The goals are to purify the glycocalyx to homogeneity, to fragment the purified glycocalyx, and to test the glycocalyx for its ability to protect mice from schistosome infection by preimmunization with the glycocalyx or its fragments. In addition, preparations of the glycocalyx that have been previously shown to increase adult worm burden will be tested for their ability to induce specific suppression. These experiments are potentially important in vaccine development. The second area of interest centers on interactions between human blood cells and schistosomula. We have previously proposed that schistosomula defend themselves against human effector cells by secreting monopalmitoyl lysophosphatidylcholine which lyses the attacking cells. We wish to test whether human monocytes adherent to the parasites show the effects of this compound in their membranes by fluorescence photobleaching recovery. Human eosinophils that have been activated with cytokines will be examined ultrastructurally to determine if they kill the parasite by the same mecha- nisms as inactivated eosinophils. Cultured eosinophils that have been activated and shifted to a hypodense phenotype will also be tested. The results will be quantitated morphometrically. In a third set of experiments, human monocyte-derived macrophages will be tested as effector cells in toxic reactions after exposure to a variety of mediators. For both monocytes and eosinophils the role of classes and subclasses of immunoglobulin prepared from patient sera in parasitic killing will be determined. These studies should define the potential capabilities of these two cell types and clarify the mechanism of parasite defense. The third area is concerned with the binding of human lipoproteins to the surface of schistosomula. The initial experiments will quantitate the binding and demonstrate its specificity. Then the ability of lipoproteins to inhibit antibody dependent cytotoxic reactions will be tested. Finally, the role of lipoproteins in worm sterol metabolism will be studied. These studies should establish whether lipoprotein binding is a defense mechanism for the parasite.
