COMPUTER SIMULATION OF IMMUNE SYSTEM FUNCTION IN SLE

SLE 免疫系统功能的计算机模拟

• 批准号: 2080783
• 负责人: OLAF A RUNQUIST
• 金额: $ 10.25万
• 依托单位: HAMLINE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-25 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2080783
• 关键词: antinuclear autoantibody; chemical binding; clearance rate; clone cells; complement; complement receptor; computer simulation; erythrocytes; human subject; immune complex; immunology; immunopathology; laboratory mouse; systemic lupus erythematosus

DESCRIPTION: (Adapted from the applicant's abstract) SLE is characterized by tissue deposition of DNA:anti-DNA IChigh anti-dsDNA titers, hypocomplementemia, low CRl receptor number per RBC and impaired Fc-and C-mediated mononuclear phagocyte system (MPS)function. None of these properties alone provides either agood correlation with or prediction of disease activity. These results suggest either a more fundamental "cause" of disease activity in SLE or that disease activity results from a combination of defects. Aims of the proposed research are to study another SLE immune system defect, namely decreased rate of RBC CRl/factor I-mediated modification of RBC-bound IC and to construct a computer simulation of immune function so that the interrelatedness of multiple immune system defects can be quantitatively recounted. Since IC modification by RBC CRl/factor I is an integral part of IC handling and is retarded in SLE, a study of factors affecting modification rates and binding properties of modified and unmodified IC will be undertaken. Specifically, the rate at which a 3H-DNA:anti-DNA:complement IC is modified will be measured as a function of a) SLE disease activity serial study, b) IC complement content, c) CRl number/RBC, and d) CRl phenotype. In addition, binding rate of modified and unmodified IC to U937 and spleen cells will be measured. These studies should increase our understanding of the biological significance of the RBC CRl/factor I-mediated modification of IC in SLE and its relationship to disease activity. The computer simulation will be constructed from a kinetic model of immune complex formation, handling and clearance. The simulation will be governed byrate constants and reagent/catalyst concentrations which regulate immune system reactions. Mathematical equations will be solved by numerical integration by The Runge-Kutta method. The simulation will enhance our understanding of the interrelatedness of immune system reactions, will be able to quantitatively predict the outcomes of multiple defects in the immune response system, and will serve as both a diagnostic and predictive technique.

描述：（改编自申请人摘要）SLE是 以DNA的组织沉积为特征：抗DNA IC高抗dsDNA 滴度、低补体血症、每个RBC的CRl受体数量低和受损 Fc和C介导的 单核吞噬细胞系统（MPS）功能。 这些特性中没有一个单独提供与 或疾病活动的预测。 这些结果表明， SLE疾病活动性或疾病活动性基本“原因 是由缺陷的组合造成的。 拟议研究的目的是 研究另一种SLE免疫系统缺陷，即红细胞生成率降低， CR 1/因子I介导的RBC结合IC的修饰，并构建一个 免疫功能的计算机模拟，以便相互关联 多个免疫系统缺陷可以被定量地重新计数。 由于IC RBC CR 1/因子I的修饰是IC处理的组成部分， 在SLE中是迟缓的，一项影响修饰率的因素的研究， 将研究改性和未改性IC的结合性能。 具体而言，3 H-DNA：抗DNA：补体IC的速率是 a）SLE疾病活动系列 研究，B）IC补体含量，c）CRl数量/RBC，和d）CRl 表型 此外，修饰的和未修饰的IC与 将测量U937和脾细胞。 这些研究应该增加 我们对红细胞CR 1/因子的生物学意义的理解 系统性红斑狼疮中碘介导的IC修饰及其与疾病的关系 活动 计算机模拟将从一个动力学模型 免疫复合物形成、处理和清除的模型。 的 模拟将由速率常数和试剂/催化剂控制 调节免疫系统反应的浓度。数学 方程组将通过龙格-库塔法进行数值积分求解 法模拟将增强我们对 相互关联的免疫系统反应，将能够 定量预测免疫系统中多种缺陷的结果， 反应系统，并将作为诊断和预测 法