The role of tunable activation thresholds in the dynamics of autoimmunity
The role of tunable activation thresholds in the dynamics of autoimmunity
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DOI：
10.1016/j.jtbi.2012.05.019
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发表时间：
2012-09-07
影响因子：
2
通讯作者：
Nicholson, L. B.
中科院分区：
文献类型：
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作者：
Blyuss, K. B.;Nicholson, L. B.
一段时间以来，人们已经知道人类自身免疫性疾病可以由病毒感染引发。已经分析了病毒和免疫系统之间相互作用的几种可能机制，普遍的观点是，在许多情况下，自身免疫的发生可以归因于“分子模拟”，其中从病毒蛋白质加工的线性肽表位模拟正常的宿主自身蛋白质，从而导致针对病毒的免疫应答与宿主细胞的交叉反应。在本文中，我们提出了一个数学模型的动态免疫反应的病毒感染和自身免疫，考虑到T细胞具有不同的激活阈值。我们展示了感染如何被免疫系统清除，以及它如何导致慢性感染或复发和缓解的复发性感染。模型的数值模拟进行说明各种动力学制度，以及分析治疗自身免疫性疾病的慢性和复发状态的潜在影响。结果提供了良好的定性协议与现有的数据对病毒感染的免疫反应和自身免疫性疾病的进展。(C)2012爱思唯尔有限公司保留所有权利。
It has been known for some time that human autoimmune diseases can be triggered by viral infections. Several possible mechanisms of interactions between a virus and immune system have been analysed, with a prevailing opinion being that the onset of autoimmunity can in many cases be attributed to "molecular mimicry", where linear peptide epitopes, processed from viral proteins, mimic normal host self-proteins, thus leading to a cross-reaction of immune response against virus with host cells. In this paper we present a mathematical model for the dynamics of an immune response to a viral infection and autoimmunity, which takes into account T cells with different activation thresholds. We show how the infection can be cleared by the immune system, as well as how it can lead to a chronic infection or recurrent infection with relapses and remissions. Numerical simulations of the model are performed to illustrate various dynamical regimes, as well as to analyse the potential impact of treatment of autoimmune disease in the chronic and recurrent states. The results provide good qualitative agreement with available data on immune responses to viral infections and progression of autoimmune diseases. (C) 2012 Elsevier Ltd. All rights reserved.