Studies on protective immunity against malaria

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1. Mechanisms of acquisition of protective immunity against malaria was investigated by comparative studies on infections with virulent plasmodium berghei (Pb NK65) and its attenuated derivative (Pb XAT) in mice. In Pb NK65 infection, mice showed suppressive response in antibody production and delayed-type hypersensitivity and development of auto antibodies against lymphocytes. Mice infected with Pb XAT did not show these responses but developed solid protective immunity against Pb NK65 infection accompanied with high antibody titer. When such an immune serum was transferred into mice Pb XAT infection was eliminated completely. These results showed that Pb XAT stimulates antibody production which contributes protection against the parasites. On the contrary, in Pb NK65 infection harmful immunopathological responses against host are more prominent than protective immune responses against the parasites. 2. Role of T cells in two aspect of immunity to Pb was examined in mice by administration of monoclonal antibodies (MAB) against T cell subsets or lymphokines. First, mice treated with anti Lyt. 2 mAb showed significantly longer survival from infection with Pb NK65 compared with intact or anti L3T4 mAb administration. This phenomenon was also observed in mice by treatment with anti gamma-IFN mAb. second, in Pb XAT infection, administration with either anti L3T4 or anti gamma-IFN mAb precluded induction of protective immunity. These findings reveal that CD4^+ T cells might be responsible for protection and CD8^+ T cells for immunopathology of the infected hosts and gamma-IFN must be effector molecules in both immune responses.