IMMUNOLOGIC STUDIES IN PRIMARY BILIARY CIRRHOSIS

原发性胆汁性肝硬化的免疫学研究

• 批准号: 3964818
• 负责人: E ANTHONY JONES
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3964818
• 关键词: B lymphocyte; T lymphocyte; affinity chromatography; biopsy; cellular pathology; complement pathway; computer simulation; cytotoxicity; density gradient ultracentrifugation; erythrocytes; gel filtration chromatography; haptens; helper T lymphocyte; human subject; human tissue; humoral immunity; hypersensitivity; immune adherence reaction; immunofluorescence technique; immunoglobulin G; immunoglobulin M; immunohematology; immunologic assay /test; immunopathology; immunosuppression; leukocyte activation /transformation; liver cirrhosis; liver disorder diagnosis; liver function; mixed lymphocyte reaction test; monocyte; orphan disease /drug; phagocytosis; radiation immunosuppression; radioimmunoassay; radiotracer; reticuloendothelial system; suppressor T lymphocyte; surface antigens; tissue /cell culture

Abnormal immune mechanisms are being studied in patients with primary biliary cirrhosis (PBC). T cell-mediated help and suppression of pokeweed mitogen-induced immunoglobulin synthesis by B cells have been studied using radioimmunoassays to measure IgG and IgM synthesized by cultures containing appropriate mixtures of different lymphocyte subpopulations in vitro. The ability of T cells to proliferate when cultured with either autologous or allogeneic irradiated B cells (mixed lymphocyte reactions) has been assessed. Results of these studies include the demonstration in PBC of (i) a diminished capacity of T cells to inhibit immunoglobulin synthesis in vitro and (ii) a deficiency of the autologous but not the allogeneic mixed lymphocyte reaction. These findings suggest that in PBC there is a fundamental defect in the interaction between autoreactive T cells and surface antigens on autologous non-T cells which leads to diminished activation of suppressor T cells and hence predisposes to a state of immune hyperresponsiveness. The coexistence of IgA deficiency and PBC has been documented. It is possible that IgA deficiency may contribute to the development of PBC, but the pathogenesis of PBC does not require IgA-dependent mechanisms. Sera from patients with PBC have been shown to contain a factor, probably an abnormally immunoreactive IgM, which blocks the binding of C3b-opsonized erythrocytes by monocytes. This finding affords a potential explanation for the C3b-receptor specific clearance defect by fixed macrophages in PBC. Patients with PBC have been shown to have diminished natural killer cell activity due to a functional defect of cytolytic effector cells. Defects of humoral immunity due to activation of subpopulations of B cells occur in this disease. For example, in PBC there is evidence compatible with the existence of an expanded clone of B cells that synthesize mitochondrial antibodies with different antigenic specificities from those synthesized by normal B cells. A disease-specific immunologic defect has

异常免疫机制正在研究中的患者原发性 胆汁性肝硬化（PBC）。 T细胞介导的美洲商陆的帮助和抑制 已经使用以下方法研究了丝裂原诱导的B细胞的免疫球蛋白合成： 放射免疫测定，以测量由含有以下物质的培养物合成的IgG和IgM 不同淋巴细胞亚群的适当混合物。 的 T细胞在与自体或 同种异体辐照B细胞（混合淋巴细胞反应）已被 评估。 这些研究的结果包括在方案预算委员会中证明： T细胞抑制免疫球蛋白合成的能力减弱， 体外和（ii）缺乏自体但不是同种异体混合 淋巴细胞反应 这些发现表明，在PBC中， 自身反应性T细胞与 自体非T细胞上的表面抗原， 抑制性T细胞的激活，因此易于免疫状态 高反应性 伊加缺乏症与PBC并存， 记录在案。 伊加缺乏症可能有助于 PBC的发展，但PBC的发病机制并不需要 IgA依赖性机制。 PBC患者的血清已被证明 含有一种因子，可能是一种异常免疫反应性IgM， 单核细胞与C3b调理红细胞的结合。 这一发现 为C3b受体特异性清除提供了一种可能的解释 PBC中固定巨噬细胞的缺陷。 PBC患者已被证明 由于功能缺陷， 溶细胞效应细胞。 由于激活的体液免疫缺陷 B细胞的亚群出现在这种疾病中。 例如，在PBC， 这与B细胞的扩增克隆的存在相一致 合成具有不同抗原性的线粒体抗体 与正常B细胞合成的特异性不同。 疾病特异性 免疫缺陷