2.50
Hdl Handle:
http://hdl.handle.net/10033/311616
Title:
A mathematical model of immune activation with a unified self-nonself concept.
Authors:
Khailaie, Sahamoddin; Bahrami, Fariba; Janahmadi, Mahyar; Milanez-Almeida, Pedro; Huehn, Jochen; Meyer-Hermann, Michael
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 naïve 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 naïve 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.
Citation:
A mathematical model of immune activation with a unified self-nonself concept. 2013, 4:474 Front Immunol
Journal:
Frontiers in immunology
Issue Date:
2013
URI:
http://hdl.handle.net/10033/311616
DOI:
10.3389/fimmu.2013.00474
PubMed ID:
24409179
Type:
Article
Language:
en
ISSN:
1664-3224
Appears in Collections:
publications of the research group system immunology ([BRICS]SIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorKhailaie, Sahamoddinen
dc.contributor.authorBahrami, Faribaen
dc.contributor.authorJanahmadi, Mahyaren
dc.contributor.authorMilanez-Almeida, Pedroen
dc.contributor.authorHuehn, Jochenen
dc.contributor.authorMeyer-Hermann, Michaelen
dc.date.accessioned2014-01-21T12:58:19Z-
dc.date.available2014-01-21T12:58:19Z-
dc.date.issued2013-
dc.identifier.citationA mathematical model of immune activation with a unified self-nonself concept. 2013, 4:474 Front Immunolen
dc.identifier.issn1664-3224-
dc.identifier.pmid24409179-
dc.identifier.doi10.3389/fimmu.2013.00474-
dc.identifier.urihttp://hdl.handle.net/10033/311616-
dc.description.abstractThe 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 naïve 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 naïve 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.en
dc.language.isoenen
dc.rightsArchived with thanks to Frontiers in immunologyen
dc.titleA mathematical model of immune activation with a unified self-nonself concept.en
dc.typeArticleen
dc.identifier.journalFrontiers in immunologyen

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