Mechanisms of over-activated innate immune system regulation in autoimmune and neurodegenerative disorders

Reactions of innate immunity include phagocytosis, the production and activity of cytokines, chemokines, and adhesion molecules, the killing of infected or changed cells by NK cells and complement activated by natural lectins, and the cytokine-dependent resistance of leukocytes to viral infection. All these mechanisms maintain innate immunity. Deficiency in this immunity is sometimes accompanied by frequent bacterial and viral infections. When innate immunity is permanently stimulated and the intensity of the reactions is stronger, these mechanisms may be directed against the host and subsequently stimulate acquired immunity (antibody and cellular immunity). A higher production of cytokines, oxidative stress, and a high production of NO accompany autoimmunity and neurodegeneration. The possible participation of innate immune receptors, cytokines, and other factors in the development of autoimmune and neurodegenerative diseases is discussed. The importance and possible role of blood-derived microglial cells in the prevention or elimination of amyloid deposits and plaque formation is described. A possible regulatory system, based on the presence of suppressors of cytokine signaling (SOCS), receptors of the Tyro-3 family, adenosine and adenosine phosphates, and IL-10, is reviewed. This review presents the mechanisms involved in the control of the innate immune response by microglia in the development of neurodegenerative disorders.