Quantititive models of CD8+ immune memory

描述(由申请人提供)：虽然免疫记忆是一个中心 脊椎动物免疫反应的特点，许多基本问题，如 至于在没有重新刺激的情况下，记忆会保持多久 无人接听。这个问题的答案是定量的，需要 除了实验研究之外，还使用了数学模型。这笔赠款 涉及到构建基于经验的模型来解决这一问题和其他问题 关于免疫记忆的问题。因为有大量的数据可用，而且 需要专注于一系列可解决的问题，拨款仅限于 细胞毒性T细胞(CD8+)反应。有两个广泛的目标： 1.量化免疫细胞的动态，以保持理论 与实验研究密切相关的模型，人们必须准确量化 免疫细胞的动态。量化扩散的理论框架 并将根据实验数据得出免疫细胞的死亡率。 2.发展记忆和曲目的定量模型。这些 模型将用来检验不同因素的相对贡献。 关于记忆的维持，并定量地估计了 在缺乏特定抗原的情况下记忆力下降。 这些模型对疫苗接种方案具有重要意义， 尤其是免疫记忆与不同疫苗之间的相互作用。 这些模型将使我们能够检验免疫记忆对一个人的影响 当接种其他疫苗时，疫苗可能会减少，这一点将被使用 建议改进疫苗接种时间表。

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.