IMMUNOREGULATION IN DISSEMINATED HISTOPLASMOSIS

这个项目的长期目标是研究……的扰动 与病原体感染相关的免疫调节 酵母菌，组织胞浆菌(HC)。播散性组织胞浆菌病的研究 (D-HPL)在近交系小鼠中，将表征可溶性抑制和辅助 受感染动物的脾细胞产生的因子和 确定它们各自作用于靶细胞的机制(S)。这个 这些因子在体内可能的生物活性也将 检查过了。实验性肺组织胞浆菌病的免疫病理学研究 将在疾病过程中通过免疫组织学染色进行研究 肉芽肿性炎症中的细胞群以连续的间隔 并对支气管肺泡灌洗液(BAL)进行类似的细胞染色。 特异性致敏T细胞和非致敏对照T细胞的流量 对肉芽肿性炎症部位进行测量。 免疫药理学研究将寻求消除抑制细胞的活性 在D-HPL小鼠身上，如果成功，将确定生物 其在寄主对HC挑战的抗性方面的意义。 有待探索的免疫治疗方法包括生产和 给受感染小鼠注射具有活性的单抗 抗抑制细胞亚群和对细胞的调节 血管紧张素转换酶对肉芽肿内的侵袭作用 抑制剂，卡托普利。在人类中，可能的数量异常 外周血免疫调节细胞群将通过 流动微量荧光法。中调节细胞亚群的功能特性 外周血液将通过体外技术进行研究，包括反向 溶血空斑试验和细胞因子产生的测定 特定的和非特定的刺激。类似的研究将在 BAL患者肺组织胞浆菌病患者获得的细胞。

The long-term obejctives of this project are to study the disturbances of immuno-regulation that are associated with infection by the pathogenic yeast, Histoplasma capsulatum (Hc). Studies of disseminated histoplasmosis (D-HPL) in inbred mice, will characterize the soluble suppressor and helper factors that are generated by spleen cells of infected animals and determine their respective mechanism(s) of action on target cells. The possible biological activities of these factors in vivo also will be examined. The immunopathology of experimental pulmonary histoplasmosis will be studied during the disease process by immunohistological staining of cell populations within granulomatous inflammation at serial intervals and by similar staining of cells in bronchoalveolar lavage (BAL) fluid. Traffic of specificity sensitized T cells and unsensitized control T cells to sites of granulomatous inflammation will be measured. Immunopharmacologic studies will seek to abrogate suppressor cell activity in mice with D-HPL and, if successful, will determine the biological significance thereof in respect to host resistance to challenge by Hc. Immunotherapeutic approaches to be explored include the production and the administration to infected mice of monoclonal antibodies with activity against suppressor cell subpopulations and, modulation of the cellular infiltrate within granulomas by the angiotensin converting enzyme inhibitor, captopril. In humans, possible quantitative abnormalities of immunoregulatory cell populations of peripheral blood will be examined by flow microfluorometry. Functional properties of regulatory cell subsets in peripheral blood will be studied by in vitro techniques including reverse hemolytic plaque assay and assays of cytokine production in response to specific and nonspecific stimuli. Similar studies will be performed on cells obtained by BAL patients with pulmonary histoplasmosis.