IMMUNOREGULATION IN DISSEMINATED HISTOPLASMOSIS

长期目标是研究微扰 与感染有关的免疫调节 致病酵母菌，组织胞浆菌(HC)。的研究 小鼠实验性肺部感染将集中在 感染肺内淋巴细胞亚群的连续变化 流鼻法鼻腔接种后间隔时间 显微荧光法和免疫组织学技术。抗原- 淋巴细胞对感染的特异性与非特异性募集 将对肺部进行研究。这些发现将与其他 白介素I和白介素II产生的测定实验 在感染过程中被来自感染肺的细胞。这个 T-L3T4辅助/诱导细胞在宿主防御中的作用 抗丙型肝炎病毒感染和调节肉芽肿性病变 炎症反应将通过给药进行检查 抗L3T4单抗GK 1.5。 未调理的HC酵母与酵母相互作用的研究 人单核细胞来源的巨噬细胞将被进行 进一步明确糖蛋白表面受体的重要性 M0是HC与巨噬细胞结合的主要部位。更多 特别是，共同的B链的家庭的作用 将测定粘附性糖蛋白CR3/LFA-1/P150-，95。 控制HC酵母吞噬和杀灭的因素将是 重点分析了干扰素γ的调节作用， 纤维连接蛋白和肉豆蔻酸酯醋酸酯。 超微结构研究将通过电子显微镜进行。 第一次审视人类体内HC的命运 巨噬细胞。有机体似乎通过的机制 本课程将重点探讨吞噬体内的躲避杀戮。 事件。 在人类中，可能的数量异常 外周血免疫调节细胞群将 用流动显微荧光法进行检测。的功能特性 外周血液中的调节细胞亚群将通过IN进行研究 细胞因子IL-1产生的体外技术 IL-2和Infy对特异性刺激和非特异性刺激的反应。 类似的研究将通过支气管肺泡对细胞进行。 肺组织胞浆菌病患者的灌洗。

Longterm objectives are to study the perturbations of immunoregulation that are associated with infection by the pathogenic yeast, Histoplasma capsulatum (Hc). Studies of experimental pulmonary infection in mice will focus on the flux of lymphocyte subpopulations within infected lungs at serial intervals after intranasal inoculation by means of flow microfluorometry and immunohistological techniques. Antigen- specific vs non-specific recruitment of lymphocytes to infected lungs will be studied. These findings will be correlated with other experiments to assay production of Interleukin I and Interleukin II by cells from infected lung during the course of infection. The role played by T-L3T4+ helper/inducer cells in host defense against Hc infection and in modulation of the granulomatous inflammatory response will be examined by administration of the anti L3T4 monoclonal antibody GK 1.5. Studies on the interactions between unopsonized Hc yeasts and human monocyte-derived macrophages will be carried out to define further the importance of a glycorprotein surface receptor on M0 as the major site for binding of Hc to macrophages. More particularly, the role of the common B chain of the family of adherence glycoproteins CR3/LFA-1/P150-,95 will be determined. Factors governing phagocytosis and killing of Hc yeasts will be analyzed with emphasis on the regulatory effects of Interferon y, fibronectin, and phorbal myristate acetate. Ultrastructural studies will be performed by electron microscopy to examine for the first time, the fate of Hc within human macrophages. Mechanisms by which the organism appears to evade killing will be explored with emphasis on intra-phagosomic events. 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 with respect to production of the cytokines IL-1 and IL-2 and INFy in response to specific and nonspecific stimuli. Similar studies will be performed on cells by bronchoalveolar lavage of patients with pulmonary histoplasmosis.