IMMUNOREGULATION IN DISSEMINATED HISTOPLASMOSIS

长期目标是研究 免疫调节与感染有关， 致病酵母，荚膜组织胞浆菌（Hc）。 研究 小鼠实验性肺部感染将集中在 感染肺内的淋巴细胞亚群 鼻内接种后的间隔时间，通过流动法 显微荧光测定法和免疫组织学技术。 抗原- 特异性与非特异性淋巴细胞募集至感染 将对肺进行研究。 这些发现将与其他 测定白细胞介素I和白细胞介素II产生的实验 在感染过程中被来自受感染肺部的细胞感染。 的 T-L3 T4+辅助/诱导细胞在宿主防御中的作用 抗HC感染和调节肉芽肿性 将通过施用本发明的组合物来检查炎症反应。 抗L3 T4单克隆抗体GK 1.5。 未经调理的Hc酵母与 将进行人单核细胞衍生的巨噬细胞， 进一步明确糖蛋白表面受体的重要性 M0上的Hc是Hc与巨噬细胞结合的主要位点。 更 特别是家族中常见的B链的作用 将测定粘附糖蛋白CR 3/LFA-1/P150- 95。 控制Hc酵母的吞噬和杀伤的因素将是 重点分析了干扰素γ的调节作用， 纤连蛋白和肉豆蔻酸醋酸佛波酯。 将通过电子显微镜进行超微结构研究 第一次检查人类中HC的命运， 巨噬细胞 生物体似乎 逃避杀死将探讨重点是内吞噬体 事件 在人类中， 外周血的免疫调节细胞群将被 通过流动显微荧光测定法检查。 功能特性 外周血中的调节细胞亚群将通过在 关于细胞因子IL-1产生的体外技术 以及IL-2和INF γ对特异性和非特异性刺激的应答。 将对支气管肺泡细胞进行类似的研究。 肺组织胞浆菌病患者灌洗。

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.