Autoimmunity and apoptosis--therapeutic implications.
Acquisition of a complex immune system during evolution provided organisms with the most effective defense mechanism against "foreign" or "non-self" invaders. This efficient protection against pathogens, however, has been achieved at the expense of a higher risk for "self"-directed reaction or autoimmunity. Establishment of self-tolerance and homeostasis in the immune system is regulated at different physiological stages of immune cells development. The breakdown in discrimination between "self" and "non-self" causes an aberrant immune response against autoantigens that promote damage to the "self" cells and tissue(s), resulting in various autoimmune phenotypes. Whereas activation and clonal proliferation of autoreactive T- and B- lymphocytes underlies the pathogenesis of autoimmune diseases, the mechanism by which self-tolerance is lost and autoimmune responses are induced is not clear yet. Autoimmunity is a multi-step process that occurs as a consequence of complex interaction between genetic susceptibility and non-genetic factors. Programmed cell death, as a key mechanism to regulate immune system function, has a crucial influence on both the selection process of immune cells and the maintenance of this immune tolerance in peripheral repertoire. Thus, defects in apoptotic death pathways may contribute to the development of autoimmune response in susceptible individuals in certain conditions.
Rashedi
Iran
I
Department of Biochemistry and General Genetics, University of Manitoba, Winnipeg, Canada.
Panigrahi
Soumya
S
Ezzati
Peyman
P
Ghavami
Saeid
S
Los
Marek
M
D000818:Animals; D017209:Apoptosis; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D007107:Immune System / Q000502:physiology*; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D001324:Autoantigens; D016207:Cytokines