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Diversity emergence and dynamics during primary immune response: a shape space, physical space model
1School of Computing, Dublin City University, Dublin 9, Ireland, jburns@computing.dcu.ie.
Theory in Biosciences = Theorie in Den Biowissenschaften
|February 1, 2008
Summary
This study models how T-cell receptor diversity and pathogen genetics influence immune system efficiency. Broad T-cell receptor activation, not just activity, indicates successful viral clearance and reduced cytotoxic lymphocyte levels.
Area of Science:
- Immunology
- Computational Biology
- Systems Biology
Background:
- T-cell receptor (TCR) diversity and pathogen genetic variation are key factors in immune response.
- Immune system states can be efficient or inefficient, impacting disease outcomes.
- Local immune dynamics influence system-wide states, particularly during primary immune responses.
Purpose of the Study:
- To present a computational model of T-cell receptor and MHC:peptide complex dynamics.
- To investigate how T-cell receptor cross-reactivity and pathogen genetic variation shape immune system states.
- To understand the relationship between local and system-wide immune dynamics and infection outcomes.
Main Methods:
- Development of a computational model combining shape space and physical space concepts.
- Simulation of immune system evolution under varying conditions of T-cell receptor cross-reactivity and pathogen genetics.
- Analysis of system-wide and local immune dynamics, including lymphatic system responses.
Main Results:
- Demonstrated that immune system efficiency is influenced by T-cell receptor cross-reactivity and pathogen genetic variation.
- Showed that localized immune dynamics significantly determine system-wide immune states.
- Modeled the emergence of highly variable clinical outcomes from similar initial infection conditions.
- Found that immune cell activity alone is not a reliable indicator of infection suppression.
Conclusions:
- Successful viral clearance is characterized by broad T-cell receptor activation in shape space.
- Effective viral clearance results in low average concentrations of activated cytotoxic lymphocyte cells.
- The model provides insights into the complex interplay of factors determining immune system effectiveness.
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