Nevo Uri, Golding Ido, Neumann A U Avidan U, Schwartz Michal, Akselrod Solange
Abramson Center for Medical Physics, School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv, Israel.
J Theor Biol. 2004 Apr 21;227(4):583-92. doi: 10.1016/j.jtbi.2003.11.031.
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.
自身耐受性,即免疫系统避免破坏机体自身组织的能力,是免疫系统正常运作的前提条件。如何实现这种自身耐受性仍是一个有争议的话题。认为自身免疫对机体构成持续威胁的观点受到了数据的挑战,这些数据表明,自身免疫在中枢神经系统遭受创伤后具有保护作用。这一发现促使我们提出“综合免疫”方法,据此自身免疫被视为免疫的一种特殊情况,即一种防御机制,它通过对抗机体内部产生或介导的潜在破坏活动的威胁来发挥作用,类似于针对外源病原体威胁的免疫防御。我们提出了一个支持这一概念的初级数学时空模型。该模型的数值解说明了针对损伤部位自身抗原的良好控制的免疫反应的有益运作。该模型还解释了日常情况下如何耐受对自身的反应。此外,我们证明,在不同调节水平下起作用的相同自身免疫反应可能导致自身免疫性疾病或退行性疾病。这个初步的定性模型支持了我们的观点,即应该修正对自身免疫的认知方式。