Laws of mechanics and function in proteins as evolved molecular machines

项目摘要/摘要 适应性免疫系统已经进化到记住最初暴露在特定抗原下并启动 对后续曝光的有效攻击。然而，像流感和艾滋病毒这样的快速进化的病毒存在 当它们发生变异时，人类免疫系统面临新的挑战，使它们更难识别和应对 在随后的曝光过程中。为了成功地对这些病原体进行二次反应，主要的 反应必须产生一种记忆反应，平衡对原始抗原的特异性和多样性 以应对随后暴露的多种可能的变种。对于一个给定物种的个体 在一个更大的群体中与其他个体互动时，给定的特异度之间的平衡的有效性 而多样性取决于许多因素，包括个人接触相同的 未来的病原体，抗原突变的速度，以及对生物过程的限制 它控制着该物种免疫记忆的产生。这项研究计划旨在 构建一个理论框架，以描述与多样性相关的利益和权衡 适应性免疫反应以及产生所述多样性的机制。然后这项研究将使用 对几个数据集的计算分析以评估不同类型的抗体应答的程度 利用老鼠和人类，物种产生的多样性水平很好地适应了它们的生物需求 作为代表性的例子。

PROJECT SUMMARY/ABSTRACT The adaptive immune system has evolved to remember primary exposures to specific antigens and launch effective attacks to subsequent exposures. However, rapidly evolving viruses like influenza and HIV present new challenges to the human immune system as they mutate, making them harder to recognize and respond to during subsequent exposures. In order for secondary responses to these pathogens to succeed, the primary response must generate a memory response that balances specificity to the original antigen with diversity against the multitude of possible variants of subsequent exposures. For an individual of a given species interacting with other individuals within a larger population, the efficacy of a given balance between specificity and diversity depends on a number of factors, including how likely the individual is to be exposed to the same pathogen in the future, the rate at which the antigen is mutating, and constraints on the biological processes which control the generation of immunological memory within that species. This research program aims to construct a theoretical framework for characterizing the benefits and trade-offs associated with diversity in the adaptive immune response and the mechanisms by which said diversity is generated. This study will then use computational analyses of several datasets to evaluate the extent to which the antibody responses of different species generate levels of diversity which are well-adapted to their biological needs, using mice and humans as representative examples.