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自身免疫动力学中的随机效应。

Stochastic Effects in Autoimmune Dynamics.

作者信息

Fatehi Farzad, Kyrychko Sergey N, Ross Aleksandra, Kyrychko Yuliya N, Blyuss Konstantin B

机构信息

Department of Mathematics, University of Sussex, Brighton, United Kingdom.

Institute of Geotechnical Mechanics, Dnipro, Ukraine.

出版信息

Front Physiol. 2018 Feb 2;9:45. doi: 10.3389/fphys.2018.00045. eCollection 2018.

Abstract

Among various possible causes of autoimmune disease, an important role is played by infections that can result in a breakdown of immune tolerance, primarily through the mechanism of "molecular mimicry". In this paper we propose and analyse a stochastic model of immune response to a viral infection and subsequent autoimmunity, with account for the populations of T cells with different activation thresholds, regulatory T cells, and cytokines. We show analytically and numerically how stochasticity can result in sustained oscillations around deterministically stable steady states, and we also investigate stochastic dynamics in the regime of bi-stability. These results provide a possible explanation for experimentally observed variations in the progression of autoimmune disease. Computations of the variance of stochastic fluctuations provide practically important insights into how the size of these fluctuations depends on various biological parameters, and this also gives a headway for comparison with experimental data on variation in the observed numbers of T cells and organ cells affected by infection.

摘要

在自身免疫性疾病的各种可能病因中,感染起着重要作用,感染主要通过“分子模拟”机制导致免疫耐受的破坏。在本文中,我们提出并分析了一个针对病毒感染及后续自身免疫的免疫反应随机模型,该模型考虑了具有不同激活阈值的T细胞群体、调节性T细胞和细胞因子。我们通过解析和数值方法展示了随机性如何导致在确定性稳定稳态周围的持续振荡,并且我们还研究了双稳态区域内的随机动力学。这些结果为实验观察到的自身免疫性疾病进展变化提供了一种可能的解释。随机波动方差的计算为这些波动的大小如何依赖于各种生物学参数提供了具有实际重要性的见解,这也为与关于受感染影响的T细胞和器官细胞观察数量变化的实验数据进行比较开辟了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c145/5801658/72b9be29cc8b/fphys-09-00045-g0001.jpg

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