A mathematical model of immune activation with a unified self-nonself concept
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 selecti...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2013-12-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00474/full |
| _version_ | 1828808858397573120 |
|---|---|
| author | Sahamoddin eKhailaie Fariba eBahrami Mahyar eJanahmadi Pedro eMilanez-Almeida Jochen eHuehn Michael eMeyer-Hermann Michael eMeyer-Hermann |
| author_facet | Sahamoddin eKhailaie Fariba eBahrami Mahyar eJanahmadi Pedro eMilanez-Almeida Jochen eHuehn Michael eMeyer-Hermann Michael eMeyer-Hermann |
| author_sort | Sahamoddin eKhailaie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T08:47:45Z |
| format | Article |
| id | doaj.art-b2e9eb2d2c5e4df9bb035ee37725ab72 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T08:47:45Z |
| publishDate | 2013-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b2e9eb2d2c5e4df9bb035ee37725ab722022-12-22T00:30:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242013-12-01410.3389/fimmu.2013.0047466087A mathematical model of immune activation with a unified self-nonself conceptSahamoddin eKhailaie0Fariba eBahrami1Mahyar eJanahmadi2Pedro eMilanez-Almeida3Jochen eHuehn4Michael eMeyer-Hermann5Michael eMeyer-Hermann6Helmholtz Centre for Infection ResearchCIPCE, School of Electrical and Computer Engineering, College of Engineering, University of TehranNeuroscience Research Centre and Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical SciencesHelmholtz Centre for Infection ResearchHelmholtz Centre for Infection ResearchHelmholtz Centre for Infection ResearchBio Centre for Life Science, Technische Universitaet BraunschweigThe 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.http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00474/fullAutoimmunityCentral TolerancePeripheral Toleranceregulatory T cellsAutoreactive T cellsimmune activation |
| spellingShingle | Sahamoddin eKhailaie Fariba eBahrami Mahyar eJanahmadi Pedro eMilanez-Almeida Jochen eHuehn Michael eMeyer-Hermann Michael eMeyer-Hermann A mathematical model of immune activation with a unified self-nonself concept Frontiers in Immunology Autoimmunity Central Tolerance Peripheral Tolerance regulatory T cells Autoreactive T cells immune activation |
| title | A mathematical model of immune activation with a unified self-nonself concept |
| title_full | A mathematical model of immune activation with a unified self-nonself concept |
| title_fullStr | A mathematical model of immune activation with a unified self-nonself concept |
| title_full_unstemmed | A mathematical model of immune activation with a unified self-nonself concept |
| title_short | A mathematical model of immune activation with a unified self-nonself concept |
| title_sort | mathematical model of immune activation with a unified self nonself concept |
| topic | Autoimmunity Central Tolerance Peripheral Tolerance regulatory T cells Autoreactive T cells immune activation |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00474/full |
| work_keys_str_mv | AT sahamoddinekhailaie amathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT faribaebahrami amathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT mahyarejanahmadi amathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT pedroemilanezalmeida amathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT jochenehuehn amathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT michaelemeyerhermann amathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT michaelemeyerhermann amathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT sahamoddinekhailaie mathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT faribaebahrami mathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT mahyarejanahmadi mathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT pedroemilanezalmeida mathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT jochenehuehn mathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT michaelemeyerhermann mathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept AT michaelemeyerhermann mathematicalmodelofimmuneactivationwithaunifiedselfnonselfconcept |