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Interrogating Individual Autoreactive Germinal Centers by Photoactivation in a Mixed Chimeric Model of Autoimmunity

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Ecoimmunity: immune tolerance by symmetric co-evolution.

Uri Nevo¹, Ehud Hauben

¹Section on Tissue Biophysics and Biomimetics, Laboratory of Integrative and Medical Biophysics, National Institute of Human Health and Child Development, National Institutes of Health, 13 South Drive, Bethesda, MD 20892, USA. nevouri@mail.nih.gov

Evolution & Development

|November 3, 2007

Summary

The Ecoimmunity model proposes that self-tolerance is a dynamic conflict between immune cells and tissue cells, not a static suppression. This co-evolutionary predator-prey system explains immune tolerance and autoimmunity.

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Area of Science:

Immunology
Systems Biology
Ecology

Background:

Immune tolerance to self is traditionally explained by central and peripheral immune system adaptations.
Mechanisms include T cell deletion, anergy, apoptosis, and regulatory T cell induction.
Existing models struggle to explain all experimental findings on immune tolerance and autoimmunity.

Purpose of the Study:

To introduce the Ecoimmunity model, viewing the immune system and tissue as a co-evolving predator-prey system.
To propose a new framework for understanding self-tolerance and autoimmunity.
To reconcile contradictory observations in immunology.

Main Methods:

Conceptual modeling based on ecological principles.
Ecological generalization applied to immunological phenomena.
Analysis of existing experimental data through the Ecoimmunity lens.

Main Results:

Self-tolerance is framed as a balanced conflict, not a suppressed equilibrium.
Tissue cells adapt phenotypically to avoid immune predation via epigenetic selection.
Self-reactive immune cells target tissue cells lacking adaptive phenotypes.

Conclusions:

The Ecoimmunity model offers a unified explanation for immune tolerance and autoimmunity.
It reconciles classical enigmas and contradictory observations in immunology.
The model provides novel predictions and potential clinical strategies.