Nevo, Golding, Neumann, Schwartz, Akselrod, 2004

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

It is generally believed that the main function of the immune system is to protect the body from foreign pathogens such as bacteria and viruses. Another important role of the immune system is to prevent the destruction of the organism's own tissues, a phenomenon known as self-tolerance. Several theories as to how the body's immune system achieves this self-tolerance have been proposed. Some of these theories have been described by mathematical models, in an attempt to elucidate the basic mechanisms underlying the autoimmune response, and also to predict its possible consequences.

When self-tolerance breaks down, the immune system synthesises antibodies against the body's own cell and tissue components. This is known as an autoimmune response, and autoimmune responses are often associated with tissue damage (such as in multiple sclerosis and rhumatoid arthritis). However, the idea that autoimmunity always has a negative effect on an organism has recently been challenged. Following traumatic injury to the central nervous system, autoimmunity can play a protective role. This led the authors of the current study to put forward the comprehensive immunity model, where autoimmunity is thought to be a defense mechanism that fights against the potential threat of self-destructive activity within an organism. This is not dissimilar to the standard immune defense that protects the body against foreign, exogenous pathogens.

In the Nevo et al. 2004 publication described here, the authors present a mathematical model which supports the idea of autoimmunity being a protective mechanism (see the figure below). The model describes self-propagating tissue damage after a focal insult. The tissue can be lost via two routes:

  • 1) Through self-perpetuating death, which is induced by the secretion of a damage-inducing factor; or

  • 2) Through immune-mediated death, (an autoimmune response)

These two methods of tissue loss compete locally for the same resource, namely the healthy tissue. In this way, the autoimmune response can stop the progression of tissue damage by firstly shifting tissue loss from the self-perpetuating route to the immune-mediated route, and then the immune-mediated pathway will cease as the feedback, stimulating signal from the self-perpetuating pathway will be lost (again, please see the figure below to make this clearer).

The complete original paper reference is cited below:

Autoimmunity as an immune defense against degenerative processes: a primary mathematical model illustrating the bright side of autoimmunity, Uri Nevo, Ido Golding, Avidan U. Neumann, Michal Schwartz, and Solange Akselrod, 2004, Journal of Theoretical Biology , 227, 583-592. (Full text (HTML) and PDF versions of the article are available on the Journal of Theoretical Biology website.) PubMed ID: 15038992

Schematic diagram of the mathematical model. Healthy cells (H) can be lost via two routes, 1) self-perpetuating death (H-N-D), or 2) immune-mediated loss (H-P-D).