Imunska toleranca: Immune tolerance

Background: Regulation of human immune system through mechanisms of immune tolerance is an exceptionally important part of the homeostasis that protects the integrity of our organism. Whenever we talk about immune responses, we primarily consider them as an efficient activation of numerous factors enabling our cellular and humoral immunity to protect us against nocive effects of various forms of pathogens. However, each of these activation processes must be adequately regulated by appropriate immunosuppressive mechanisms, thereby providing a rational extent of immune reactivity without exhausting the organism and at the same time assuring a rather quick reestablishment of normal physiological conditions, which is a basic task of immune homeostasis. Such natural and dynamic yin/yang balance, being crucialfor the wellbeing of each individual, can only be provided by well orchestrated specific interactions between activated effector immune cells, such as Th1, Th2 and Th17 CD4+ lymphocytes, CD8+ cytotoxic T lymphocytes, natural killer cells (NK) and other activating factors on one side, and the oppositely functioning immunoregulatory effectors, such as regulatory CD4+ andCD8+ T lymphocytes, tolerogenic antigen-presenting cells (APC) and other immunosuppressive factors, on the other. In the case of a colapse or an imbalance of this system, there are serious consequences that are reflected inthe occurrence of autoimmune diseases, in which case the immune system is unsuccessfully suppressing the reactivity against self-antigens or the outburst of cancer cells, due to the excessive negative regulatory immune mechanisms that are actively protecting tumors. Conclusions: In this review weare presenting novel findings regarding the mechanisms of tolerance as an important part of immune homeostasis and discussing the potential of translating this knowledge into clinical setting by developing advanced cell therapies, mostly for treating autoimmune diseases and preventing graft rejection following allogeneic tissue and organ transplantation. Izhodišča: Mehanizmi imunske tolerance so pomemben del homeostaze imunskega sistema, ki zagotavlja celovitost našega organizma. Ko govorimo o imunskem odzivu, največkrat pomislimo na učinkovito aktiviranje številnih dejavnikov, ki omogočajo, da se s pomočjo celične in protitelesne oziroma humoralne imunosti uspešno obranimo pred škodljivim delovanjem najrazličnejših telesu tujih snovi in dejavnikov. Pri tem pa večinoma ne razmišljamo o tem, da mora biti vsak aktivacijski obrambni mehanizem uravnan z nasprotno delujočim, zaviralnim procesom. S tem je namreč zagotovljen ustrezen obseg imunske reaktivnosti brez nepotrebnega in škodljivega izčrpavanja organizma ter razmeroma hitro vračanje na raven normalnega, uravnoteženega fiziološkega stanja, kar je osnovni cilj delovanja homeostaznih mehanizmov. Tako naravno, dinamično ravnovesje jin/jang , ki je ključno za zdravje vsakega posameznika,lahko zagotavlja le dobro nadzorovano in uravnoteženo delovanje efektorskih imunskih celic, in sicer tako aktiviranih limfocitov CD4+, vrste Th1, Th2 in Th17, citotoksičnih limfocitov CD8+, naravnih celic ubijalk (NK), limfocitov B in ostalih aktivacijskih dejavnikov na eni strani ter nasprotno delujočih imunosupresivnih celic, med katere uvrščamo različne vrste regulatornih CD4+ in CD8+ limfocitov T in tolerogenih antigene-predstavljajočih celic (APC) ter ostale zaviralne dejavnike, na drugistrani. V kolikor se to ravnovesje poruši in nagne na eno ali drugo stran, se lahko pojavijo bodisi avtoimunske bolezni, ki so posledica nepreprečene reaktivnost zoper lastne antigene, ali pa nebrzdan razrast rakavih celic zaradi prekomernega negativnega imunskega uravnavanja, ki lahko popolnoma izniči protitumorske efektorske mehanizme imunskega sistema. Zaključki: V našem prispevku predstavljamo najnovejša dognanja na področju preučevanja in razumevanja mehanizmov imunske tolerance, ki je pomembni del homeostaze pri človeku, ter potencialne možnosti za njihovo terapevtsko uporabo v obliki naprednega celičnega zdravljenja predvsem avtoimunskih bolezni ter pri preprečevanju zavrnitvenih odzivov po alogenskih presaditvah tkiv in organov.