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初始CD8 T细胞免疫反应的数学模型:一个非线性年龄结构系统的稳定性分析

Mathematical model of the primary CD8 T cell immune response: stability analysis of a nonlinear age-structured system.

作者信息

Terry Emmanuelle, Marvel Jacqueline, Arpin Christophe, Gandrillon Olivier, Crauste Fabien

机构信息

Université de Lyon, Université Lyon 1, CNRS UMR 5208, Institut Camille Jordan, 43 blvd du 11 novembre 1918, 69622, Villeurbanne-Cedex, France.

出版信息

J Math Biol. 2012 Aug;65(2):263-91. doi: 10.1007/s00285-011-0459-8. Epub 2011 Aug 13.

Abstract

The primary CD8 T cell immune response, due to a first encounter with a pathogen, happens in two phases: an expansion phase, with a fast increase of T cell count, followed by a contraction phase. This contraction phase is followed by the generation of memory cells. These latter are specific of the antigen and will allow a faster and stronger response when encountering the antigen for the second time. We propose a nonlinear mathematical model describing the T CD8 immune response to a primary infection, based on three nonlinear ordinary differential equations and one nonlinear age-structured partial differential equation, describing the evolution of CD8 T cell count and pathogen amount. We discuss in particular the roles and relevance of feedback controls that regulate the response. First we reduce our system to a system with a nonlinear differential equation with a distributed delay. We study the existence of two steady states, and we analyze the asymptotic stability of these steady states. Second we study the system with a discrete delay, and analyze global asymptotic stability of steady states. Finally, we show some simulations that we can obtain from the model and confront them to experimental data.

摘要

由于首次接触病原体,初始CD8 T细胞免疫反应分两个阶段发生:一个是扩增阶段,T细胞数量快速增加,随后是收缩阶段。收缩阶段之后是记忆细胞的产生。这些记忆细胞是抗原特异性的,当第二次遇到抗原时会产生更快更强的反应。我们提出了一个非线性数学模型,基于三个非线性常微分方程和一个非线性年龄结构偏微分方程,描述CD8 T细胞免疫反应对初次感染的响应,该模型描述了CD8 T细胞数量和病原体数量的演变。我们特别讨论了调节该反应的反馈控制的作用和相关性。首先,我们将系统简化为一个具有分布延迟的非线性微分方程系统。我们研究了两个稳态的存在性,并分析了这些稳态的渐近稳定性。其次,我们研究了具有离散延迟的系统,并分析了稳态的全局渐近稳定性。最后,我们展示了从该模型获得的一些模拟结果,并将它们与实验数据进行对比。

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