a mathematical model of immune activation with a unified self-nonself concept

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ID: 240355
2013
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Abstract
The adaptive immune system reacts against pathogenic nonself, whereas it normally remains tolerant to self. The initiation of an immune response requires a critical antigen(Ag)-stimulation and a critical number of Ag-specific T cells. Autoreactive T cells are not completely deleted by thymic selection and partially present in the periphery of healthy individuals that respond in certain physiological conditions. A number of experimental and theoretical models are based on the concept that structural differences discriminate self from nonself. In this article, we establish a mathematical model for immune activation in which self and nonself are not distinguished. The model considers the dynamic interplay of conventional T cells, regulatory T cells (Tregs) and IL-2 molecules and shows that the renewal rate ratio of resting Tregs to naive T cells as well as the proliferation rate of activated T cells determine the probability of immune stimulation. The actual initiation of an immune response, however, relies on the absolute renewal rate of naive T cells. This result suggests that thymic selection reduces the probability of autoimmunity by increasing the Ag-stimulation threshold of self reaction which is established by selection of a low number of low-avidity autoreactive T cells balanced with a proper number of Tregs. The stability analysis of the ordinary differential equation model reveals three different possible immune reactions depending on critical levels of Ag-stimulation: A subcritical stimulation, a threshold stimulation inducing a proper immune response, and an overcritical stimulation leading to chronic co-existence of Ag and immune activity. The model exhibits oscillatory solutions in the case of persistent but moderate Ag-stimulation, while the system returns to the homeostatic state upon Ag clearance. In this unifying concept, self and nonself appear as a result of shifted Ag-stimulation thresholds which delineate these three regimes of immune activation.
Reference Key
ekhailaie2013frontiersa Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Sahamoddin eKhailaie, Fariba eBahrami, Mahyar eJanahmadi, Pedro eMilanez-Almeida, Jochen eHuehn, Michael eMeyer-Hermann
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Journal sudebno-meditsinskaia ekspertiza
Year 2013
DOI
10.3389/fimmu.2013.00474
URL
http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00474/full
Keywords
autoimmunity regulatory t cells allergy

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