MECHANISMS OF NONSTERILIZING IMMUNITY IN MALARIA

介导小鼠对急性夏氏疟原虫疟疾的抗性 通过非抗体免疫机制。 连续性细胞转移研究 证明T细胞是诱导和表达所必需的 这种形式的免疫。 拟议研究的目的是 确定脾T细胞的哪些Lyt亚群参与其中。 Lyt子集 正常胸腺小鼠脾细胞，通过选择性杀死 在补体存在下或通过淘选的抗Lyt单克隆抗体 大鼠抗小鼠Lyt包被的脾细胞在用抗大鼠Lyt包被的培养皿上 将IG注射到组织相容的无胸腺裸鼠中，然后 Chadaudi Adami的挑战。 由此产生的寄生虫血症将是 绘制时间图，以查看哪个Lyt子集抑制 感染 此外，从小鼠脾制备的脾细胞的Lyt亚群 P. chabaudi adami免疫B细胞缺陷小鼠以及免疫学 将测试完整小鼠的过继转移能力 放射性同种抗原对夏氏疟原虫感染免疫力 受惠人士 为了明确P. 用脾构建的Chabaudi adami T细胞克隆和T细胞杂交体 免疫小鼠的细胞将测试它们保护裸鼠的能力 对抗挑战性感染 同样，来自保护性的可溶性因子 将对细胞系进行表征并检测其介导 保护裸鼠。 将研究另外两个参数，以确定 它们是否与Lyt分数实现的保护相关 T细胞克隆和T细胞杂交。 这些是脾脏巨噬细胞激活 如通过化学发光和脾网状细胞活化所测定的， 细胞 最后，将夏氏疟原虫adami抗原分级分离， 其特征在于它们激活保护细胞的能力 群体以及通过免疫在小鼠中诱导保护。 这种方法试图将保护与细胞联系起来 功能、因子产生和效应细胞活化，可以提供一种 事件的连贯的生理图片，必须为 抗体非依赖性免疫的表达。

Resistance to acute Plasmodium chabaudi adami malaria in mice is mediated by non-antibody mechanisms of immunity. Adoptive cell transfer studies demonstrate that T cells are required for both the induction and expression of this form of immunity. The purpose of the proposed study is to determine which Lyt subsets of splenic T cells are involved. Lyt subsets of spleen cells from euthymic mice prepared by selective killing with anti-Lyt monoclonal antibody in the presence of complement or by panning rat anti-mouse Lyt coated spleen cells on petri plates coated with anti-rat Ig will be injected into histocopatible athymic nude mice prior to challenge with P. chadaudi adami. The resulting parasitemias will be plotted against time in order to see which Lyt subset(s) suppress infection. Also, Lyt subsets of spleen cells prepared from the spleens of P. chabaudi adami immune B-cell deficient mice as well as immunologically intact mice will be tested for their ability to adoptively transfer immunity to P chabaudi adami infection to irradiated homologous recipients. In order to define mechanisms of nonantibody immunity to P. chabaudi adami T-cell clones and T-cell hybrids constructed with spleen cells of immune mice will be tested for their capacity to protect nude mice against challenge infection. Similarly, soluble factors from protective cell lines will be characterized and tested for their ability to mediate protection in nude mice. Two additional parameters will be investigated in order to determine whether they can be correlated with protection achieved with Lyt fraction T-cell clones and T-cell hybrids. These are splenic macrophage activation as determined by chemiluminescence and the activation of splenic reticular cells. Finally, P. chabaudi adami antigens will be fractionated and characterized in terms of their ability to activate protecting cell populations as well as to induce protection in mice by immunization. This approach, which will attempt to correlate protection with cell function, factor-production, and effector cell activation, may provide a coherent physiologic picture of events which must transpire for the expression of antibody-independent immunity.