Quantititive models of CD8+ immune memory

描述（由申请人提供）：虽然免疫记忆是一个核心的 脊椎动物免疫反应的特点，许多基本问题，如 在没有再刺激的情况下，记忆能维持多久， 无人回应这个问题的答案是定量的，需要 除了实验研究之外，还使用数学模型。这笔赠款 包括构建基于几何的模型来解决这个问题和其他问题， 关于免疫记忆的问题由于可获得的数据丰富， 需要专注于一系列可解决的问题，补助金仅限于 细胞毒性T细胞（CD8+）应答。有两大目标： 1.量化免疫细胞的动态，为了保持理论上的 与实验研究紧密相关的模型，人们必须准确地量化 免疫细胞的动力学量化增殖的理论框架 并从实验数据中得出免疫细胞的死亡率。 2.发展记忆和记忆库的定量模型。这些 模型将被用来检查不同因素的相对贡献 对记忆维持的影响，并定量估计 在缺乏特异性抗原的情况下记忆衰退。 这些模型对疫苗接种方案具有重要意义， 特别是关于不同疫苗的免疫记忆之间的相互作用。 这些模型将使我们能够研究免疫记忆对一个人的免疫力的影响， 当接种其他疫苗时，疫苗可能会下降，这将用于 建议改进疫苗接种计划。

DESCRIPTION (provided by the applicant): While immune memory is a central feature of the immune response of vertebrates, many fundamental questions, such as how long memory will be maintained in the absence of re-stimulation, remain unanswered. The answer to this question is quantitative in nature, and requires the use of mathematical models in addition to experimental research. This grant involves the construction of empirically-based models to address this and other questions on immune memory. Because of the wealth of data available and the need to focus on a soluble set of problems, the grant is limited to the cytotoxic T-cell (CD8+) responses. There are two broad objectives: 1. Quantifying the dynamics of immune cells, In order to keep the theoretical models closely tied to experimental research, one has to accurately quantify the dynamics of immune cells. A theoretical framework to quantify proliferation and death rates of immune cells from the experimental data will be developed. 2. Development of quantitative models for memory and the repertoire. These models will be used to examine the relative contributions of different factors on the maintenance of memory, and to quantitatively estimate the rate of decline of memory in the absence of specific antigen. These models have important implications for vaccination protocols, particularly on the interactions between immune memory to different vaccines. The models will allow us to examine how the rate at which immune memory to one vaccine may decline when other vaccines are administered, and this will be used to suggest improved schedules for vaccination.