The immunological paradox of pregnancy: a reappraisal

The survival of the allogeneic conceptus has long been an immunological paradox. Medawar was the first to propose an evasive mechanism based on the concept of self/non-self recognition described in classical transplantation immunology. Since then, several newer models of self/non-self recognition have been proposed, such as the PAMP/PRR system, the Missing Self and the Danger Hypothesis. The present paper considers the fetal-maternal relationship in the context of all these models. The conclusion reached is that none of them is really appropriate because the interface between trophoblast cells of the fetal placenta and the leukocytes of the maternal decidua is unique. Pregnancy is not simply a case of acceptance or rejection like a transplant. The immunological mechanism must provide a balanced environment whereby the conceptus is nurtured by the mother and yet prevented from excessive invasion. Future identification of trophoblast ligands and their respective receptors on uterine Natural Killer cells and other leukocytes is likely to offer the best insight as to how this symbiotic state is achieved.