COMPUTER MODELS OF THE IMMUNE SYSTEM

我们建议使用现代大规模计算来开发和分析 免疫系统关键方面的技术、模型和 了解免疫调节的终极目标。很难做到 在没有数学模型的情况下理解一个大的 根据非线性动力学定律相互作用的元素系统。 因为体内现象涉及到大量的 免疫系统组件，体外实验未能提供答案 许多关键问题。 我们寻求开发新一代模型，我们可以用它来探索： (1)免疫复合体在免疫调节中的作用。它已经被证明了 在体外，当免疫复合物跨越Fc-γ受体和表面时 B细胞上的免疫球蛋白受体，抑制B细胞增殖 而差异化可能会产生。免疫复合体也结合毛囊 树突状细胞，它们可能在那里保留并长时间刺激B细胞 一段时间。因为免疫复合体作为抗原形成和分解 抗体浓度变化时，复杂的反馈机制可以 诱导性。我们的模型将解决这种控制如何在体内发挥作用。(2)何时 拾取抗原抗体或独特型(ID)抗ID复合体， 由B细胞处理并呈递给T细胞，这种现象被称为 分子内的帮助可以发生，借此B细胞可以从非 抗原特异性T细胞。将开发模型以探索 这一现象在免疫网络、抗id疫苗治疗中的意义 和自身免疫性疾病。(3)网络模型遗漏了重要的 功能，如T细胞的帮助，免疫复合物的调节，自身的作用 和异源抗原，并区分B-1和B-2细胞。我们 建议审查这种修改的影响。(4)B细胞 成年动物表达的曲目会影响动物的反应能力 为了疾病。我们将使用我们的模型来研究网络交互如何 导致表达T15独特型的细胞在 对细菌多糖磷胆碱的反应。 最重要的是，在开发综合模型方面的进展将 加深对免疫系统运作的了解 作为一个整体与疾病作斗争。加深对免疫的理解 监管可以帮助设计新的治疗方法和治疗方法 自身免疫性疾病、细菌感染、过敏等免疫系统 精神错乱。

We propose to develop and analyze, using modern large scale computing techniques, models of critical aspects of the immune system with the ultimate goal of understanding immune regulation. It is difficult to comprehend in the absence of mathematical models the operation of a large system of elements that interact according to nonlinear dynamical laws. Because in vivo phenomenon involve interactions among large numbers of immune system components, in vitro experiments fail to provide answers to many crucial questions. We seek to develop a new generation of models with which we can explore : (1) The role of immune complexes in immune regulation. It have been shown in vitro that when immune complexes span Fc-gamma receptors and surface immunoglobulin receptors on B cells, inhibition of B cell proliferation and differentiation can result. Immune complexes also bind follicular dendritic cells, where they may be retained and stimulate B cells for long periods of time. Because immune complexes form and breakup as antigen and antibody concentrations change, complex feedback mechanisms can be induced. Our models will address how such controls work in vivo. (2) When antigen-antibody or idiotypic (id) anti-id complexes are picked up, processed and presented by B cells to T cells, a phenomena known as intramolecular help can occur, whereby B cells can obtain help from non- antigen specific T cells. Models will be developed to explore the implications of this phenomena in immune networks, anti-id vaccine therapy and autoimmune disease. (3) Network models have left out important features, such as T cell help, immune complex regulation, effects of self and foreign antigen, and distinguishing between B-1 and B-2 cells. We propose to examine the influences of such modifications. (4) The B cell repertoire expressed by an adult influences an animal's ability to respond to disease. We will use our models to examine how network interactions can lead to clonal dominance of cells expressing the T15 idiotype in the response to the bacterial polysaccharide phosphorylcholine. Most important is that progress in developing comprehensive models will provide an increased understanding of the operation of the immune system as a whole in fighting disease. Increased understanding of immune regulation can help in the design of new treatments and therapies for autoimmune disease, bacterial infection, allergies and other immune system disorders.