IMMUNOLOGY OF THE SCHISTOSOME EGG GRANULOMA

血吸虫卵肉芽肿的免疫学

• 批准号: 2059935
• 负责人: DOV L BOROS
• 金额: $ 23.78万
• 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 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2059935
• 关键词: B lymphocyte; Schistosoma mansoni; T lymphocyte; cellular immunity; collagen; complementary DNA; delayed hypersensitivity; density gradient ultracentrifugation; granuloma; humoral immunity; immunoglobulin idiotypes; immunoglobulins; immunoregulation; inflammation; interleukin 2; laboratory mouse; laboratory rabbit; macrophage; migration inhibition factor; monoclonal antibody; protein biosynthesis; 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.

该研究项目包括对细胞的细胞/分子分析， 免疫调节、炎症和纤维化机制活跃于 曼氏肉芽肿血吸虫病 我们的目标是阐明 肉芽肿过程和设计免疫干预，以改善 肉芽肿病理学 研究目标分为4个方面 相互关联的领域： 1.用离体受精卵诱导T抑制细胞 肉芽肿中抗原、独特型-抗独特型（id-抗id）相互作用 调制 用单克隆抗体分离Ts细胞诱导抗原， 抗体和免疫亲和性。 传入、传出TS细胞的诱导是 在体内和体外验证。 T细胞功能中的id-抗id相互作用， 检查肉芽肿调制。 过早调制 血吸虫病是通过免疫学手段寻找的。 2.肉芽肿T淋巴细胞功能研究及白细胞介素2的作用 （IL-2）在肉芽肿过程中。 炎症模式（TDH）和TS 淋巴细胞相互作用在活跃的、调节的肉芽肿中进行分析。 IL-2受体显示IL-2、炎性淋巴因子的意义 在肉芽肿形成的生产进行了评估，调节作用， 肉芽肿TS细胞与淋巴因子产生中的id-抗id相互作用 并且证实肉芽肿调节。 3.肝脏的分级、蛋白质型、功能表征， 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的巨噬细胞是 通过密度梯度离心分离。 检查每个馏分 对于成熟标记物，通过免疫荧光、吞噬、分泌和 辅助/调节功能。 集落刺激因子在乳腺癌中的作用 单核细胞供应和肉芽肿巨噬细胞周转。 4.功能性肉芽肿中胶原同种型的合成和再吸收 肉芽肿成纤维细胞的研究， 卵抗原 肉芽肿胶原同种型的合成和吸收是 在未治疗和药物治愈的小鼠中进行生物化学和胶原蛋白描绘 特异性cDNA探针。 增殖和胶原蛋白合成比较， 成纤维细胞的活力和调制肉芽肿。 中性 评估再吸收中的蛋白酶-蛋白酶抑制剂。 孤立卵 检测抗原的成纤维细胞增强/细胞病变效应。