STUDIES IN PROGRESSIVE IMMUNE KIDNEY DISEASE

进行性免疫性肾病的研究

• 批准号: 3230799
• 负责人: CURTIS B WILSON
• 金额: $ 15.02万
• 依托单位: SCRIPPS CLINIC AND RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3230799
• 关键词: Goodpasture's syndrome; antibody formation; autoimmune disorder; basement membrane; cell bank /registry; clone cells; complement; complement fixation tests; disease /disorder model; electron microscopy; glomerulonephritis; helper T lymphocyte; humoral immunity; immune complex; immunization; immunofluorescence technique; immunopathology; interleukin 2; interstitial nephritis; lymphocyte; macrophage; model design /development; monoclonal antibody; neutrophil; radioimmunoassay; radiotracer; suppressor T lymphocyte

Available information indicates that antibody mechanisms initiate most experimental and human glomerulonephritis. Much less is known about the immune mechanisms, humoral or cellular, responsible for tubulointerstitial nephritis (TIN). Even with the information available and the use of aggressive therapeutic maneuvers to modulate nephritogenic antibody responses, damage often progresses relentlessly to renal failure necessitating costly and only partially satisfactory measures such as dialysis. Studies herein will quantitate the humoral and cellular mechanisms leading to initiation, evolution, progression, and/or regression of immunologically-induced autoimmune models of TIN in the rat using nephritogenic anti-tubular basement membrane (TBM) antibodies and effector T cell lines and clones. Assessment of the contributions of antibody and immune cells and their clones will be defined during the evolutionary stages of sequential antibody deposition, polymorphonuclear leukocyte accumulation, and subsequent lymphocyte and monocyte/macrophage dominated stages of TIN in the Brown Norway (BN) rat induced with heterologous TBM in adjuvants. A new model of cell-mediated and transferrable nodular TIN produced in the Lewis (LEW) rat by immunization with BN renal basement membrane (RBM) will be studied using similar techniques for comparison to the antibody related BN TIN. The factors controlling the nephritogenic autoimmune responses including their induction and modulation will be elucidated. These studies entail modulation of cell surface receptors and study of the mechanisms of induction of disease resistance using attenuated T cell lines. It will be necessary to identify the antigens reactive with the humoral and cellular immune elements involved. The LEW rat, with proper immunization, develops anti-basement membrane antibodies similar to those seen in human Goodpasture's syndrome. This serious human disease is currently lacking a model to examine the poorly understood immunopathogenesis of the not infrequent episodic and sometimes fatal pulmonary hemorrhage of these patients. The immunized LEW rat will be explored as a potential model for detailed investigation of the pathogenesis of this immunologically-induced lung injury.

可用信息表明抗体机制启动最多 实验和人肾小球肾炎。 关于 免疫机制，体液或细胞，负责肾小管间隙 肾炎（锡）。 即使有可用的信息和使用 激进的治疗性操纵以调节肾病性抗体 反应，损害通常会不懈地发展为肾衰竭 需要成本高昂，只需要部分令人满意的措施，例如 透析。 这里的研究将定量体液和细胞 导致启动，进化，进步和/或回归的机制 使用大鼠免疫诱导的锡的自身免疫模型 肾病性抗管状基底膜（TBM）抗体和效应子 T细胞线和克隆。 评估抗体和 免疫细胞及其克隆将在进化期间定义 顺序抗体沉积，多形核白细胞的阶段 积累，随后的淋巴细胞和单核细胞/巨噬细胞主导 棕色挪威（BN）大鼠的TIN阶段，由异源TBM诱导 佐剂。 细胞介导的和转移结节锡的新模型 用BN肾脏地下室免疫在刘易斯（Lew）大鼠中产生 膜（RBM）将使用类似技术进行研究，以进行比较 与抗体相关的BN锡。 控制肾病的因素 自身免疫反应（包括其诱导和调节）将是 阐明。 这些研究需要调节细胞表面受体和 研究使用衰减的诱导疾病抗性的机制 T细胞系。 有必要识别与 涉及的体液和细胞免疫元件。 le鼠，带有 适当的免疫，形成类似于 那些在人类的综合综合症中看到的人。 这种严重的人类疾病是 目前缺乏模型来检查知之甚少 不经常发作的免疫病发生，有时是致命的 这些患者的肺出血。 免疫的le鼠将是 作为详细研究的潜在模型探索 这种免疫学诱导的肺损伤的发病机理。