IMMUNOLOGIC STUDIES IN PRIMARY BILIARY CIRRHOSIS

原发性胆汁性肝硬化的免疫学研究

• 批准号: 3918248
• 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/3918248
• 关键词: B lymphocyte; T lymphocyte; antibody formation; autoimmune disorder; biliary tract disorder; biopsy; cellular pathology; complement pathway; computer simulation; human subject; human tissue; humoral immunity; immunochemistry; immunoglobulin M; immunohematology; immunosuppression; laboratory mouse; leukocyte activation /transformation; liver cirrhosis; liver disorder diagnosis; macrophage; mixed lymphocyte reaction test; orphan disease /drug; reticuloendothelial system; surface antigens; tissue /cell culture

Primary biliary cirrhosis (PBC) appears to be a model autoimmune disease. Abnormal immune mechanisms are being studied in this disease, but so far a disease-specific immunologic deficit has not been defined with certainty. Recently recognized defects of humoral immunity include: (i) Evidence for the existence of an expanded clone of activated B cells that synthesize mitochondrial antibodies with different antigenic specificities from those synthesized by normal B cells; and (ii) Detection of a serum factor, probably an abnormally immunoreactive IgM, which blocks the binding of C3b-opsonized erythrocytes by monocytes. The latter finding affords a potential explanation for the C3b-receptor specific clearance defect by fixed macrophages in PBC. Recently recognized defects in cellular immunity include: (i) A diminished ability of patient T cells to suppress immunoglobulin synthesis; (ii) The presence of increased numbers of circulating activated B cells; and (iii) Hyporeactivity of lymphocytes in the autologous mixed lymphocyte reaction, which normally leads to activation of suppressor T cells. To determine whether such abnormalities of lymphocyte function in PBC might be due to altered function of immunoregulatory T cell subpopulations, phenotypic and functional characteristics of T cells that have the CD4 antigen detectable (by monoclonal antibody) on their surface were examined. In contrast to normal subjects and patients with other liver diseases, patients with PBC were found to have defects in CD4+, Leu-8+ T cell-mediated suppression of immunoglobulin synthesis and mitogen-stimulated proliferation. These defects may play a central role in the defective immunoregulation found in this disease.

原发性胆汁性肝硬变(PBC)似乎是一种自身免疫模型 疾病。异常的免疫机制正在研究中。 疾病，但到目前为止，疾病特异性免疫缺陷还没有 被确定地定义了。最近发现的缺陷 体液豁免包括：(1)存在体液豁免的证据 合成线粒体的活化B细胞的扩增克隆 具有不同抗原性的抗体 由正常B细胞合成；和(Ii)检测血清 因子，可能是一种异常免疫反应的IgM，它阻止了 单核细胞与C3b调理红细胞的结合。后者 这一发现为C3b受体提供了一个潜在的解释 PBC中固定巨噬细胞的特异性清除缺陷。最近 公认的细胞免疫缺陷包括：(1)细胞免疫缺陷 患者T细胞抑制免疫球蛋白合成的能力； (2)循环中活化B的数量增加 细胞；以及(Iii)自体淋巴细胞的低反应性 混合淋巴细胞反应，这通常会导致 抑制性T细胞。以确定这种异常情况是否 PBC中的淋巴细胞功能可能是由于PBC的功能改变 免疫调节性T细胞亚群，表型和功能 具有可检测到的CD4抗原的T细胞的特征(通过 检测其表面的单抗)。相比之下， 对于正常受试者和其他肝病患者， 有PBC者被发现存在缺陷的CD4+、Leu-8+T细胞介导 抑制免疫球蛋白合成和丝裂原刺激 扩散。这些缺陷可能会在以下方面发挥核心作用 在这种疾病中发现的免疫调节缺陷。