IMMUNOREGULATION IN DISSEMINATED HISTOPLASMOSIS

播散性组织胞浆菌病的免疫调节

• 批准号: 3127165
• 负责人: Ward E Bullock
• 金额: $ 17.85万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-09-01 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3127165
• 关键词: B lymphocyte; Staphylococcus aureus; acid phosphatase; antiviral antibody; binding proteins; cell cell interaction; cell population study; cellular immunity; cytokine; flow cytometry; glycoproteins; histoplasmosis; human subject; immunoregulation; immunosuppression; inflammation; interleukin 2; laboratory rat; lymphokines; macrophage; microorganism immunology; monoclonal antibody; monocyte; opsonin; phagocytosis; pneumonia; radiotracer; suppressor T lymphocyte; tissue /cell culture

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.

长期目标是研究扰动 与感染相关的免疫调节 致病性酵母菌，荚膜组织胞浆菌 (Hc)。 研究 小鼠实验性肺部感染将集中于 连续感染肺内的淋巴细胞亚群 鼻内流动接种后的间隔时间 显微荧光测定和免疫组织学技术。 抗原- 淋巴细胞向感染者的特异性与非特异性募集 将研究肺部。 这些发现将与其他发现相关 测定白细胞介素 I 和白细胞介素 II 产生的实验 感染过程中来自受感染肺部的细胞。 这 T-L3T4+辅助/诱导细胞在宿主防御中发挥的作用 对抗 Hc 感染并调节肉芽肿 炎症反应将通过施用来检查 抗L3T4单克隆抗体GK 1.5。 非调理 Hc 酵母与 Hc 酵母之间相互作用的研究 人类单核细胞来源的巨噬细胞将被用于 进一步定义糖蛋白表面受体的重要性 M0 是 Hc 与巨噬细胞结合的主要位点。 更多的 特别是，家族的共同B链的作用 将确定粘附糖蛋白 CR3/LFA-1/P150-,95。 控制 Hc 酵母吞噬和杀死的因素将是 重点分析了干扰素 y 的调节作用， 纤连蛋白和佛巴尔肉豆蔻酸酯乙酸酯。 超微结构研究将通过电子显微镜进行 首次检验 Hc 在人类体内的命运 巨噬细胞。 有机体表现出的机制 将探索逃避杀戮，重点是吞噬体内 事件。 在人类中，可能出现数量异常 外周血中的免疫调节细胞群 通过流式显微荧光测定法进行检查。 功能特性 外周血中的调节细胞亚群将由 in 细胞因子 IL-1 生产的体外技术 IL-2 和 INFy 对特异性和非特异性刺激作出反应。 类似的研究将通过支气管肺泡细胞进行 肺组织胞浆菌病患者的灌洗。