Autoimmunity and Alloimmunity – by Products of Adoptive Immunity and Sources of Anti-tumor Immunity Failure

MD Bubanovic^a, S Najman MD PhD^b

^aDepartment of Obstetrics and Gynecology – “Medica Center” - Nis, Serbia and Montenegro, ^bInstitute for Biology, University Medical School – Nis, Serbia and Montenegro

In all vertebrates, a functional immune system is able to react against foreign antigens while remaining unresponsive to self-antigens. This self-tolerance is acquired and maintained by combination of central and peripheral tolerances. There are evidences that many auto-immune diseases and alloimmunity are characteristic of vertebrates and that they are associated with MHC molecules. The protective mechanisms which evolved in response to the auto-immunity-imposed evolutionary pressure or, more precisely, co-evolved with the phenomenon of auto-immunity, are related to various forms of immune tolerance, strong and multileveled control immunomodulatory and suppressive factors like sex hormones, IL-10, TGF-, Th2 activity, apoptosis and/or anergy of self reactive clones, blood-barrier sequestration of “self” molecules, cells, tissues and organs. In addition, with the appearance of viviparity and placentation as possible models of natural allotransplantation, the phenomenon of alloimmunity acquired the role of factor of selection pressure. Alloimmunity can be another by-product of evolution of the adoptive immunity which emerged under selection pressure of microbes and “latently” accumulated enormous strength. With the emergence of viviparous mammals, the further evolution of adoptive immunity and reproduction became closely associated with alloimmunity as a new powerful factor of selection pressure in direct connection with reproductive efficacy. As in the case of autoimmunity, selection pressure of alloimmunity caused the emergence of fine mechanisms for the control of immune reaction on one hand and absence of expression of MHC molecules on placental tissues, on the other – except for monomorphic and low-polymorphic MHC class Ib molecules. Controlling mechanisms for the prevention of auto-immunity are very similar to mechanisms of immunotolerance in pregnancy and mechanisms of tumor escape. Therefore, controlling/protective mechanisms of immunotolerance in pregnancy could represent a more effective and sophisticated advancement of the controlling mechanisms for the prevention of auto-immunity. In addition, there are large body of data that same or very similar controlling/protective mechanisms are included in tumor escape.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 1091 (Vaccine trials).