A better understanding of the mechanisms of protective immunity to malaria are still needed. Previous studies from this laboratory have determined that there are important differences in the immune response to non-lethal and lethal P. yoe1ii17x malaria and in the responses of malaria- susceptible, compared with resistant mice. We will now extend these studies to another species of rodent malaria, P. chabaudi. In order to further understand the differences between lethal and non-lethal malaria, we will analyze the activities of subpopulations of T helper cells and T cytotoxic cells during the course of malaria infections by analyzing the lymphokines produced during infection and the isotypes of Ig produced. We will also determine whether lymphocytes from mice with non-lethal infections and resistant mice consistently produce higher levels of gamma- IFN and whether their splenic macrophages secrete enhanced levels of hydrogen peroxide, compared with mice with lethal infections. Other studies from this laboratory have indicated that Pc96, an antigen on the surface of Plasmodium chabaudi infected erythrocytes, is partially protective in mice and may induce cell-mediated immunity. In the studies proposed, we will investigate the mechanism of protection induced by immunization with this antigen using transfer of subpopulations of lymphocytes and immune serum. We will also use this antigen in immunization studies with lymphokines as adjuvants.