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IMMUNOREGULATION IN HUMAN SCHISTOSOMIASIS

人类血吸虫病的免疫调节

基本信息

批准号：
3444751
负责人：
Barbara L Doughty
金额：
$ 10.26万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1988-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3444751
关键词：
B lymphocyte T lymphocyte cell cell interaction delayed hypersensitivity enzyme linked immunosorbent assay granuloma helminthic antigen host organism interaction human subject immunoregulation lymphokines schistosomiasis suppressor T lymphocyte tissue /cell culture

项目摘要

Experimental murine models of schistosomiasis mansoni have characterized the delayed type hypersensitivity cellular responses to eggs lodged in the tissues of the host. The cell types involved in the early acute granulomatous responses are lymphocytes (T cells, B cells and plasma cells), macrophages (monocytes, epitheloid cells and giant cells) fibroblasts, granulocytes (eosinophils, neutrophils), and mast cells (1-6). Furthermore, studies of granulomatous hypersensitivity in murine schistosomiasis have demonstrated a role for lymphocyte subsets in granuloma formation (7, 8). Previously published studies using an in vitro granuloma model established a role for T cell subsets in granuloma formation and identified a suppressor T cell pathway in granuloma modulation (9, 10). This proposal outlines in vitro technology which will enable the investigator to analyze granulomatous hypersensitivity without risk to the patient from invasive surgical procedures. A thorough understanding of chronic granulomatous disease in schistosomiasIs and the immunologic factors that contribute to or ameliorate morbidity will provide sound rationale for the development of either prophylactic protocols or clinical treatments that might reduce or ameliorate morbidity. Other investigators have identified immunoregulatory mechanisms operative in human schistosomiasis. These mechanisms were defined using antigen or mitogen induced proliferation of peripheral blood mononuclear cells and include serum factors, adherent mononuclear cells and suppressor T cells (11-20). This proposal intends to examine granuloma formation and modulation in human schistosomiasis, using an in vitro bead granuloma model which recapitulates the process of delayed type hypersensitivity granulomas, and to provide new knowledge of cell-cell interactions which result in the development of chronic granulomatous disease. The objectives of this proposal are to determine the role of human T cell subsets on granuloma formation and modulation, and to characterize the function of the T cell subsets as to inducer, effector or suppressor, and to correlate the immunoregulatory circuits with the degree of clinical morbidity.

曼氏血吸虫病的实验小鼠模型的特征在于迟发型超敏反应细胞的反应，以鸡蛋停留在宿主的组织。参与早期急性心肌梗死的细胞类型肉芽肿反应是淋巴细胞（T细胞、B细胞和血浆细胞）、巨噬细胞（单核细胞、上皮样细胞和巨细胞）成纤维细胞、粒细胞（嗜酸性粒细胞、中性粒细胞）和肥大细胞（1-6）。此外，对小鼠肉芽肿性超敏反应的研究血吸虫病已经证明了淋巴细胞亚群在肉芽肿形成（7，8）。先前发表的研究使用体外肉芽肿模型确立了T细胞亚群在肉芽肿中的作用形成，并确定了抑制性T细胞途径在肉芽肿调制（9，10）。该提案概述了体外技术，使研究者能够分析肉芽肿性超敏反应，侵入性外科手术对患者的风险。的透彻对小儿慢性肉芽肿性疾病的认识有助于或改善发病率免疫因素将提供制定预防性方案或可能减少或改善发病率的临床治疗。其他研究人员已经确定了免疫调节机制，人类血吸虫病。这些机制是使用抗原或丝裂原诱导的外周血单核细胞增殖，包括血清因子、粘附单核细胞和抑制性T细胞（11-20）。该建议旨在检查肉芽肿形成，使用体外珠粒肉芽肿模型调节人血吸虫病它概括了迟发型超敏反应的过程肉芽肿，并提供细胞间相互作用的新知识，导致慢性肉芽肿性疾病的发展。目标这项建议的目的是确定人类T细胞亚群在肉芽肿形成和调节，并表征 T细胞亚群作为诱导剂，效应剂或抑制剂，并将T细胞亚群与诱导剂，效应剂或抑制剂相关联。免疫调节回路与临床发病率的关系。