TY - JOUR
T1 - Autoimmunity as an immune defense against degenerative processes
T2 - A primary mathematical model illustrating the bright side of autoimmunity
AU - Nevo, Uri
AU - Golding, Ido
AU - Neumann, Avidan U.
AU - Schwartz, Michal
AU - Akselrod, Solange
PY - 2004/4/21
Y1 - 2004/4/21
N2 - Self-tolerance, or the ability of the immune system to refrain from destroying the organism's own tissues, is a prerequisite for proper immune system operation. How such self-tolerance is achieved is still a subject of debate. The belief that autoimmunity poses a continuous threat to the organism was challenged by data demonstrating that autoimmunity has a protective function after traumatic injury to the central nervous system. This finding led us to suggest the 'comprehensive immunity' approach by which autoimmunity is viewed as a special case of immunity, namely as a defense mechanism that operates by fighting against the threat of potential destructive activity originated or mediated within the organism, similarly to the immune defense that operates against the threat from exogenous pathogens. We present a primary mathematical spatio-temporal model that supports this concept. The numerical solutions of this model illustrate the beneficial operation of a well-controlled immune response specific to self-antigens residing in the site of lesion. The model also explains how the response to self might be tolerated on a day-to-day basis. In addition, we demonstrate that the same autoimmune response, operating at different levels of regulation, can lead to either an autoimmune disease or a degenerative disorder. This preliminary qualitative model supports our contention that the way autoimmunity is perceived should be revised.
AB - Self-tolerance, or the ability of the immune system to refrain from destroying the organism's own tissues, is a prerequisite for proper immune system operation. How such self-tolerance is achieved is still a subject of debate. The belief that autoimmunity poses a continuous threat to the organism was challenged by data demonstrating that autoimmunity has a protective function after traumatic injury to the central nervous system. This finding led us to suggest the 'comprehensive immunity' approach by which autoimmunity is viewed as a special case of immunity, namely as a defense mechanism that operates by fighting against the threat of potential destructive activity originated or mediated within the organism, similarly to the immune defense that operates against the threat from exogenous pathogens. We present a primary mathematical spatio-temporal model that supports this concept. The numerical solutions of this model illustrate the beneficial operation of a well-controlled immune response specific to self-antigens residing in the site of lesion. The model also explains how the response to self might be tolerated on a day-to-day basis. In addition, we demonstrate that the same autoimmune response, operating at different levels of regulation, can lead to either an autoimmune disease or a degenerative disorder. This preliminary qualitative model supports our contention that the way autoimmunity is perceived should be revised.
KW - Autoimmune disease
KW - Autoimmunity
KW - Mathematical model
KW - Multiple sclerosis
KW - Neuronal degeneration
KW - Self-tolerance
UR - http://www.scopus.com/inward/record.url?scp=1642294055&partnerID=8YFLogxK
U2 - 10.1016/j.jtbi.2003.11.031
DO - 10.1016/j.jtbi.2003.11.031
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C2 - 15038992
AN - SCOPUS:1642294055
SN - 0022-5193
VL - 227
SP - 583
EP - 592
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
IS - 4
ER -