Studies on protective immunity against malaria

1.通过对伯氏疟原虫(PbNK65)及其减毒衍生物(PbXAT)感染小鼠的比较研究，探讨了小鼠获得疟疾保护性免疫的机制。在铅NK65感染中，小鼠表现出抗体产生抑制反应和迟发性超敏反应，并产生抗淋巴细胞的自身抗体。感染PbXAT的小鼠未表现出这些反应，但对PbNK65感染并伴有高抗体滴度的小鼠产生了坚实的保护性免疫。将此免疫血清转移到小鼠体内，可完全消除PbXAT感染。这些结果表明，PbXAT刺激抗体的产生，从而对寄生虫具有保护作用。相反，在PbNK65感染中，针对寄主的有害免疫病理反应比针对寄生虫的保护性免疫反应更为突出。2.用抗T细胞亚群或淋巴因子的单抗，观察了T细胞在小鼠铅免疫的两个方面的作用。首先，用抗Lyt治疗的小鼠。2单抗与完整单抗或抗L3T4单抗相比，抗铅NK65单抗的存活时间明显延长。在用抗-γ-干扰素单抗治疗的小鼠中也观察到了这种现象。第二，在PbXAT感染中，用抗L3T4或抗γ-干扰素单抗均不能诱导保护性免疫。这些结果表明，在感染宿主的免疫病理过程中，CD4^+T细胞可能起到保护作用，CD8^+T细胞和γ-干扰素可能是这两种免疫应答中的效应分子。

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.