COMPUTER SIMULATION FOR IMMUNOLOGICAL EXPERIMENTS

描述：(改编自申请人的摘要)本提案 涉及免疫计算机模型的第二阶段开发 系统及其在大型中国细胞实验中的应用 合作、亲和力成熟、自我认可和调节 回应。申请人已使用 元胞自动机概念。它包含了许多共识 免疫系统的特征，EQ，A细胞，B细胞和T细胞， 个体中受体的多样性和MHC II类分子的多样性 胸腺中T细胞的群体、阴性和阳性选择， 竞争性细胞-抗原和细胞-免疫复合体相互作用 由A和B细胞处理，将多肽递呈给T细胞 MHC的背景，B和T细胞的克隆性生长导致记忆。这个 申请人表示，已经有可能开发出一种现实的 相互作用参数的校准，使得模型响应于 引入抗原作为一种可靠的、即使是最小的免疫系统。这个 计算机模型也显示了适应性和能力 从经验中学习。这个模型显示出成为一部小说的希望 免疫学家手中的工具。申请人表示，虽然 模拟可能不能替代生物学工作，但它们可能会指导 并进行核实。此外，申请人辩称，一些将军 假说可以在手头没有生物学验证的地方得到检验。 出于技术或经济原因。 在拟议的项目中，申请人打算复制一个有限的 免疫学假设的数量，并检验最近的假设 在每一种情况下都是有效的。这将通过以下方式完成：为每个 案例，基本模型的修改和运行实验 根据这一假设。这将在密切的互动中完成 与实验系统的作者或提出者进行交流。具体的 该建议的目的是研究以下内容：a)所涉及的因素 尤其是在免疫反应的亲和力成熟过程中 分别评估克隆选择的影响，然后通过 抗原结合和V基因的超突变；b) T细胞潜在免疫原肽的显性/隐蔽性，以及 这一特性在自体胸腺选择中的预期效果 侵袭性细胞与自身免疫；c)产生和调节 类风湿因子在正常免疫反应中的作用 抗Fc B淋巴细胞可将异源多肽呈递给T细胞的假说 细胞在结合免疫复合体之后，因此享有假定的帮助 克隆生长。模拟还应指出后果和 预防全身性自身免疫的可能调节因素。

DESCRIPTION: (Adapted from the applicant's abstract) This proposal concerns the second stage development of a computer model of the immune system and its use in performing in ma china experiments on cell cooperation, affinity maturation, self recognition and regulation of the response. The applicant has constructed the basic system using the cellular automaton concept. It incorporates a number of consensus features of the immune system, e.q., A cells, B cells and T cells, diversity of receptors in the individual and of the MHC class II in the population, negative and positive selection of T cells in the thymus, competitive cell-antigen and cell-immune complex interaction, antigen processing by A and B cells, presentation of peptides to T cells in the context of MHC, clonal growth of B and T cells resulting in memory. The applicant states that it has been possible to develop a realistic calibration of interaction parameters, such that the model responds to the introduction of antigen as a credible, if minimal, immune system. The computer model was also shown to display adaptability and the capacity to learn from experience. The model shows promise of becoming a novel tool in the hands of immunologists. The applicant states that although the simulations may not substitute for biological work, they may guide and verify it. Moreover, the applicant argues that some general hypotheses could be tested where no biological verification is at hand for technical or economic reasons. In the proposed project the applicant intends to reproduce a limited number of immunological scenarios and to test the recent hypotheses prevailing in each case. This will be done by introducing, for each case, modifications of the basic model and by running experiments according to the hypothesis. This will be done in close interactions with the authors or proposers of the experimental systems. The specific aims of the proposal are to study the following: a) the factors involved in the affinity maturation of the immune response, in particular assessing separately and then together the impact of clonal selection by antigen binding and by hypermutation of the V genes; b) the concept of dominance/crypticity of peptides potentially immunogenic for T cells, and the expected effect of this property in thymic selection of auto- aggressive cells and autoimmunity; c) the production and regulation of rheumatoid factor during normal immune responses according to the hypothesis that anti-Fc B-lymphocytes can present foreign peptides to T cells after binding immune complexes, and thus enjoy putative help for clonal growth. The simulation should also indicate the consequences and the probable regulatory factors to prevent generalized autoimmunity.