IMMUNOREGULATION IN MURINE MALARIA

用非致死性分离株快速解决感染的小鼠品系 约氏疟原虫非常容易感染致命的 分离出同一种寄生虫 同样， 在感染致命的约氏疟原虫后存活时间最长的人 感染了非致命的隔离物 宿主反应表型 每种情况都是由基因控制的，也受H-2基因的影响。 作为H-2复合体外的基因。 实验被提议为 研究各种近交、H-2同源和重组近交小鼠品系， 识别，映射和表征H-2和非H-2基因， 宿主抵抗感染的能力 寄生虫特异性体液和 细胞免疫反应，因为它们发生在选定的小鼠品系，将是 在感染不同约氏疟原虫的整个过程中， 分离株 ELISA、FIPA和Western印迹分析将用于 表征约氏疟原虫特异性抗体应答。 细胞介 将通过DTH在体内和通过细胞在体外分析反应。 增殖和差异淋巴因子产生（TI-2、IL-4、IFN γ 和TNF）。 T细胞Western和 Mishell-Dutton培养物将用于表征细胞亚群 调解这些反应。 最后，我们将确定是否 未感染红细胞表面寄生虫诱导的抗体 与细胞表面的寄生虫抗原或正常细胞发生反应 细胞表面分子 这个项目的长期目标是解释 一组宿主基因是如何调节 对约氏疟原虫分离株感染的敏感性增加，但 使宿主对相关分离株的感染具有相对抵抗力 同一种寄生虫

Strains of mice which quickly resolve infections with a nonlethal isolate of Plasmodium yoelii are exquisitely susceptible to infection with a lethal isolate of this same parasite species. Likewise, strains of mice which live longest following infection with lethal P. yoelii are most susceptible to infection with the nonlethal isolate. The host response phenotype in each case is genetically controlled, and is influenced by H-2 genes as well as genes mapping outside the H-2 complex. Experiments are proposed to study various inbred, H-2 congenic, and recombinant inbred mouse strains to identify, map, and characterize the H-2 and non-H-2 genes which influence the host's ability to resist infection. Parasite-specific humoral and cellular immune responses, as they occur in selected mouse strains, will be characterized throughout the course of infection with different P. yoelii isolates. ELISA, FIPA, and Western blot analyses will be used to characterize the P. yoelii-specific antibody responses. Cell-mediated responses will be analyzed in vivo by DTH, and in vitro by cell proliferation and differential lymphokine production (TI-2, IL-4, IFN gamma and TNF) following stimulation with P. yoelii antigens. T cell Western and Mishell-Dutton cultures will be used to characterize the subsets of cells mediating these responses. finally, we will determine whether or not the parasite-induced antibodies on the surface of uninfected red blood cells are reacting with parasite antigens on the cell surface, or with normal cell surface molecules. The long range goal of this project is to explain how a single set of host genes can regulated responses which mediate increased susceptibility to infection with on isolate of P. yoelii, yet render the host comparatively resistant to infection with a related isolate of the same parasite species.