MODELLING CELL MEDIATED IMMUNE RESPONSES IN THE COMPUTER

描述（由申请人提供）：计算建模，如果适当的话 使用，是一种有价值的方式来解开和理解免疫的复杂性， 系统，如果允许轻描淡写的话， 自从十年前我们开始建设IMMSIM。今天，随着我们 动机完好无损，我们的代码更复杂，我们想展示 结果获得了一个更完整的免疫系统在machina。这项建议 介绍了今后三年的持续努力， 一个模型的全部潜力，现在能够复制多种 参与免疫防御。这个雄心勃勃的计划的决定性一步 是构建免疫的“细胞”分支，并将其连接到 最初的体液反应模型，在目前的NIH下完成的一项工作， 授予R 01 AI 042262.由于已知病毒感染， T效应细胞和抗体的共同作用才能克服 感染通过使用大量不同的病毒，我们确定了 他们的行为参数对受感染的生物体的命运，并看到 这两种反应的相对价值因情况而异， 也取决于病毒的构成作为一项紧急发现，我们 发现体液和细胞分支经常处于竞争状态， 在回应中互相阻挠。在接下来的三年里， 将追求的目标：a）完成各种行为参数的阵列， 病毒，并研究其对防御策略的影响， 感染的生物体; B）研究感染期间病毒突变的影响 以及免疫系统的对抗措施;以及c）确定 初级和次级刺激之间的免疫原性缺口（例如，之间 疫苗和入侵者），以建议，最终， 设计

DESCRIPTION (provided by the applicant): Computational modeling, if properly used, is a valuable way to unravel and comprehend the complexity of the Immune System, which - if an understatement is allowed - has not grown any simpler since a decade ago, when we began the construction of IMMSIM. Today, with our motivation intact, and our codes more sophisticated, we want to show the results obtained with a more complete immune system in machina. This proposal describes continuing efforts for the next three years intended to capture the full potential of a model that is now able to reproduce many kinds of engagement of the immune defense. The decisive step in this ambitious program was to construct the "cellular" branch of immunity and to splice it on to the original humoral response model, a deed accomplished under the current NIH grant R0lAI042262. The test target was infection by virus, since it is known that the work of both T effector cells and antibodies is required to conquer the infection. By using a large diversity of viruses we determined the weight of their behavioral parameters for the fate of the infected organism, and saw that the relative merit of the two responses was different from case to case, and was also dictated by the makeup of the virus. As an emergent finding, we discovered that humoral and cellular branches are often in competition and thwart each other during the response. Over the next three years, the following aims will be pursued: a) complete the array of diverse behavioral parameters of the virus and investigate their effect on the defense strategies of the infected organism; b) investigate the effect of virus mutation during infection and the countermoves of the immune system; and c) determine the impact of immunogenicity gaps between primary and secondary stimulation (e.g., between vaccine and invader) in order to suggest, eventually, guidelines for vaccine design.