IMMUNOREGULATION IN MURINE MALARIA

用非致命性分离株快速解决感染的小鼠品系 约氏疟原虫极易感染致死的 分离出同样的寄生虫物种。同样，一些品系的小鼠 感染致死性约氏杆菌后最长的寿命是最容易受到影响的 感染这种非致命性的分离物。中的寄主反应表型 每个病例都是由基因控制的，也受到H-2基因的影响 因为基因定位在H-2复合体之外。建议进行实验，以 研究各种近交系、H-2同源和重组近交系小鼠以 识别、定位和表征影响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 在选定的小鼠品系中发生的细胞免疫反应将是 在感染不同约氏杆菌的整个过程中表现出的特点 分离株。将使用ELISA、FIPA和Western印迹分析来 确定约氏疟原虫特异性抗体反应的特征。细胞介导的 体内反应将通过DTH进行分析，体外将通过细胞进行分析 增殖和不同淋巴因子的产生(TI-2、IL-4、干扰素-γ 和肿瘤坏死因子)。T细胞Western和 米歇尔-达顿培养将被用来表征细胞亚群 调停这些反应。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反应，或与正常 细胞表面分子。这个项目的长期目标是解释 一组宿主基因如何调节中介反应 约氏疟原虫分离株对感染的易感性增加，但 使宿主对相关菌株的感染具有相对抵抗力 属于同一种寄生虫。

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.