Stewart J, Varela F J, Coutinho A
Centre d'Etudes Transdisciplinaires, Paris, France.
J Autoimmun. 1989 Jun;2 Suppl:15-23. doi: 10.1016/0896-8411(89)90113-3.
According to a classical, antigen-driven view of the immune system, autoimmunity is due to the presence of self-reactive lymphocyte clones which have not been eliminated. However, computer simulations of the immune network show that the greater the degree of connectivity of a clone, the greater its degree of tolerance to chronic antigenic stimulation. This tolerance does not correspond to an absence of response on the part of the system as a whole. On the contrary, stimulation by a 'tolerogenic antigen' results in widespread modification and overall activation of the whole network. This suggests that on an autopoietic network view of the immune system, autoimmunity arises not because of the presence of self-reactive clones, which is completely normal, but because such clones are inadequately connected to the network. This amounts to a complete reversal in perspective, whose significance for the clinical treatment of autoimmunity and the future of immunology is discussed.
根据免疫系统的经典抗原驱动观点，自身免疫是由于未被清除的自身反应性淋巴细胞克隆的存在。然而，免疫网络的计算机模拟表明，克隆的连接程度越高，其对慢性抗原刺激的耐受程度就越高。这种耐受并不等同于整个系统没有反应。相反，由“致耐受性抗原”刺激会导致整个网络的广泛修饰和整体激活。这表明，从免疫系统的自组织网络观点来看，自身免疫的产生不是因为自身反应性克隆的存在（这是完全正常的），而是因为这些克隆与网络的连接不充分。这相当于观点的彻底转变，文中讨论了其对自身免疫临床治疗和免疫学未来的意义。
