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Stochastic Effects in Autoimmune Dynamics

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 a...

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Autores principales: Fatehi, Farzad, Kyrychko, Sergey N., Ross, Aleksandra, Kyrychko, Yuliya N., Blyuss, Konstantin B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801658/
https://www.ncbi.nlm.nih.gov/pubmed/29456513
http://dx.doi.org/10.3389/fphys.2018.00045
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author Fatehi, Farzad
Kyrychko, Sergey N.
Ross, Aleksandra
Kyrychko, Yuliya N.
Blyuss, Konstantin B.
author_facet Fatehi, Farzad
Kyrychko, Sergey N.
Ross, Aleksandra
Kyrychko, Yuliya N.
Blyuss, Konstantin B.
author_sort Fatehi, Farzad
collection PubMed
description 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.
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spelling pubmed-58016582018-02-16 Stochastic Effects in Autoimmune Dynamics Fatehi, Farzad Kyrychko, Sergey N. Ross, Aleksandra Kyrychko, Yuliya N. Blyuss, Konstantin B. Front Physiol Physiology 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. Frontiers Media S.A. 2018-02-02 /pmc/articles/PMC5801658/ /pubmed/29456513 http://dx.doi.org/10.3389/fphys.2018.00045 Text en Copyright © 2018 Fatehi, Kyrychko, Ross, Kyrychko and Blyuss. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Fatehi, Farzad
Kyrychko, Sergey N.
Ross, Aleksandra
Kyrychko, Yuliya N.
Blyuss, Konstantin B.
Stochastic Effects in Autoimmune Dynamics
title Stochastic Effects in Autoimmune Dynamics
title_full Stochastic Effects in Autoimmune Dynamics
title_fullStr Stochastic Effects in Autoimmune Dynamics
title_full_unstemmed Stochastic Effects in Autoimmune Dynamics
title_short Stochastic Effects in Autoimmune Dynamics
title_sort stochastic effects in autoimmune dynamics
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801658/
https://www.ncbi.nlm.nih.gov/pubmed/29456513
http://dx.doi.org/10.3389/fphys.2018.00045
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