Day2015 - Early cellular innate and adaptive immune responses to ischemia/reperfusion injury and solid organ allotransplantation
Model Identifier
MODEL1911190001
Short description
This is an ordinary differential equation model of the early inflammatory response during transplantion. Descriptions are included of the inflammatory events associated with the initial surgical procedure, the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft, and the inflammatory effects of T cells.
Format
SBML
(L2V4)
Related Publication
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Mathematical modeling of early cellular innate and adaptive immune responses to ischemia/reperfusion injury and solid organ allotransplantation
- Day, J.D., Metes, D.M., Vodovotz, Y.
- Frontiers in Immunology , 9/ 2015 , Volume 6 , DOI: 10.3389/fimmu.2015.00484
- Department of Mathematics, University of Tennessee, Knoxville, TN, United States
- A mathematical model of the early inflammatory response in transplantation is formulated with ordinary differential equations. We first consider the inflammatory events associated only with the initial surgical procedure and the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft. These events release damage-associated molecular pattern molecules (DAMPs), thereby initiating an acute inflammatory response. In simulations of this model, resolution of inflammation depends on the severity of the tissue damage caused by these events and the patient's (co)-morbidities. We augment a portion of a previously published mathematical model of acute inflammation with the inflammatory effects of T cells in the absence of antigenic allograft mismatch (but with DAMP release proportional to the degree of graft damage prior to transplant). Finally, we include the antigenic mismatch of the graft, which leads to the stimulation of potent memory T cell responses, leading to further DAMP release from the graft and concomitant increase in allograft damage. Regulatory mechanisms are also included at the final stage. Our simulations suggest that surgical injury and I/R-induced graft damage can be well-tolerated by the recipient when each is present alone, but that their combination (along with antigenic mismatch) may lead to acute rejection, as seen clinically in a subset of patients. An emergent phenomenon from our simulations is that low-level DAMP release can tolerize the recipient to a mismatched allograft, whereas different restimulation regimens resulted in an exaggerated rejection response, in agreement with published studies. We suggest that mechanistic mathematical models might serve as an adjunct for patient- or sub-group-specific predictions, simulated clinical studies, and rational design of immunosuppression.
Contributors
Submitter of the first revision: Johannes Meyer
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer
Metadata information
hasProperty (2 statements)
Curation status
Non-curated
Modelling approach(es)
Tags
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
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Model files |
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| Day2015.xml | SBML L2V4 Representation of Day2015 - Early cellular innate and adaptive immune responses to ischemia/reperfusion injury and solid organ allotransplantation | 80.34 KB | Preview | Download |
Additional files |
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| Day2015.cps | COPASI file of Day2015 - Early cellular innate and adaptive immune responses to ischemia/reperfusion injury and solid organ allotransplantation | 155.83 KB | Preview | Download |
- Model originally submitted by : Johannes Meyer
- Submitted: Nov 19, 2019 12:12:23 PM
- Last Modified: Nov 19, 2019 12:12:23 PM
Revisions
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Version: 1
- Submitted on: Nov 19, 2019 12:12:23 PM
- Submitted by: Johannes Meyer
- With comment: Import of Day2015 - Early cellular innate and adaptive immune responses to ischemia/reperfusion injury and solid organ allotransplantation