IMMUNOREGULATION OF THE SCHISTOSOME EGG GRANULOMA

血吸虫卵肉芽肿的免疫调节

• 批准号: 3480705
• 负责人: DOV L BOROS
• 金额: $ 18.36万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-06-01 至 1992-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3480705
• 关键词: B lymphocyte; T lymphocyte; cellular immunity; complementary DNA; delayed hypersensitivity; density gradient ultracentrifugation; granuloma; humoral immunity; immunoglobulins; immunoregulation; inflammation; interleukin 2; macrophage; migration inhibition factor; monoclonal antibody; schistosomiasis; subcutaneous fibrosis; suppressor T lymphocyte; thymectomy

This research project comprises the cellular/molecular analysis of the immunoregulatory, inflammatory and fibrotic mechanisms active in granulomatous schistosomiasis mansoni. Our objective is to elucidate the granulomatous process and design immunologic interventions to ameliorate granulomatous pathology. The research objectives are divided into 4 interrelatled areas: 1. Induction of T suppressor (TS) cells with isolated schistosome egg antigen, idiotype-antiidiotype (id--anti id) interactions in granuloma modulations. Ts cell inducer antigen is isolated with monoclonal antibodies and immunoaffinity. Induction of afferent, efferent TS cells is verified in vivo, in vitro. Id-anti id interactions in T cell functions, granulomal modulation are examined. Premature modulation of schistosomiasis is sought by immunologic means. 2. Functional studies on granuloma T lymphocytes, the role of interleukin 2 (IL-2) in the granulomatous process. Mode of inflammatory (TDH) and TS lymphocyte interaction is analyzed in the vigorous, modulated granulomas. The significance of IL-2 receptor display IL-2, inflammatory lymphokine production in granuloma formation is evaluated, the regulatory role of granuloma TS cells and id-anti id interactions in lyumphokine production and granuloma modulation is confirmed. 3. Fractionation, pyhenotypic, functional characterization of liver, intestinal granuloma macrophages, monocyte supply-macrophage turnover. Macrophages isolated from enzymatically dispersed granulomas are fractionated by density gradient centrifugation. Each fraction is examined for maturation markers by immunofluorescence, phagocytic, secretory and accessory/regulatory functions. Role of colony stimulating factor in monocyte supply and granuloma macrophage turnover is elucidated. 4. Collagen isotype synthesis and resorption in granulomas, functional studies on the granuloma fibroblast, isolation of fibrogenic factor from egg antigens. Granuloma collagen isotype synthesis and resorption is delineated in untreated and drug cured mice biochemically and with collagen specific cDNA probes. Proliferation and collagen synthesis are compared in fibroblasts of the vigorous and modulated granulomas. Neutral protease-protease inhibitors in resorption are assessed. Isolated egg antigen is examined for fibroblast enhancing/cytopathic effect.

这项研究项目包括对细胞/分子的分析 免疫调节、炎症和纤维化机制活跃在 肉芽肿性曼氏血吸虫病。我们的目标是澄清 肉芽肿过程和设计免疫干预措施以改善 肉芽肿性病理。研究目标分为4个部分 相互关联的领域： 1.用分离的血吸虫卵诱导T抑制(TS)细胞 肉芽肿中的抗原、独特型-抗独特型(id-抗id)相互作用 调制。用单抗分离TS细胞诱导物抗原 抗体和免疫亲和力。传入、传出TS细胞的诱导 在体内和体外进行了验证。T细胞功能中的ID-抗ID相互作用， 肉芽组织的调节被检查。过早地调节 血吸虫病是通过免疫学手段寻找的。 2.肉芽肿T淋巴细胞的功能研究，白介素2的作用 (IL-2)在肉芽肿过程中的表达。炎症模式(TDH)和TS 淋巴细胞的相互作用在活跃的、调节的肉芽肿中被分析。 IL-2受体表达IL-2、炎性淋巴因子的意义 在肉芽肿形成中的生产被评估，其调节作用 淋巴因子产生中肉芽肿TS细胞与id-抗id相互作用 肉芽肿的调制被证实。 3.肝脏的分级、表型、功能特征， 肠肉芽肿巨噬细胞、单核细胞供应-巨噬细胞周转。 从酶分散的肉芽肿中分离出的巨噬细胞 用密度梯度离心法进行分级。每一部分都要经过检查 免疫荧光、吞噬、分泌和免疫荧光检测成熟标志 附属/监管职能。集落刺激因子在细胞周期调控中的作用 单核细胞供应和肉芽肿巨噬细胞周转被阐明。 4.肉芽肿中的胶原同型合成和吸收，功能性 肉芽肿成纤维细胞的研究及成纤维因子的分离 卵子抗原。肉芽肿胶原蛋白同型合成和吸收 在未经治疗和药物治愈的小鼠中用胶原蛋白进行生化描绘 特异的cdna探针。增殖和胶原合成在 生动性和调节性肉芽肿的成纤维细胞。中性 对吸收中的蛋白水解酶-蛋白水解酶抑制剂进行了评估。离体卵 对成纤维细胞增强/细胞病变效应的抗原进行检测。