Evolution of (our) Concepts on Key Determinants of a Successful Pregnancy

Abstract

In this paper, I outline briefly the concepts that led to the evolution of Reproductive Immunology. The history starts in 1971, with the "Medawar paradigm", and as a consequence in the 70 s-90 s, the placental barrier and immunosuppression concepts were proposed. The first conceptual breakthrough started with the "vaccination against abortion in mice", leading to immunotrophysm, and the importance of cytokines emerged, which lead to the disapproval of the Th1:Th2 paradigm. It was necessary to revise this approach, and, notably, it was recognized that NK cells were not only "bad guys", but in fact were required for successful pregnancy. NK cells are involved in the transformation of the local vessels. We are interest in the control of NK activation by various interleukins (notably the Il-12, IL-18, NK tripod) as well as tumour necrosis factor-related weak inducer of apoptosis (TWEAK) in mice and human.One must now recognize "suppression" as Tregs emerged, and recognize signals of the embryo. We also discuss here FF G-CSF and sHLA-G. Microarrays, as well as studies on innate immunity, which are amongst our latest interests, while combining studies in mice and human, with spin off consequences for the clinician.

Feto-Marenal Interactions – Undisputable Evidence for the Concept of Neuroimmune Biology

“…Finally it became gradually clear that the immune system plays a very active role during gestation. It helps actively growth and development of the fetus with growth factors, cytokines and possible even classical hormones [3]. The immune system is capable of producing cytokines, chemokines and also classical hormones, which is delivered into target areas, such as the fetus [4].…”

“…NK cells are involved in the transformation of the local vessels. NK cells are activated by Il-12, IL-18, NK tripod, and by tumour necrosis factor-like, weak inducer of apoptosis (TWEAK) in mice and human [3]. Uterine natural killer (uNK) cells will ultimately represent up to 50%-70% of the cellular content of the basal decidual stroma.…”

“…Recently regulatory T cells (Tregs) emerged, which recognize signals of the embryo. Newly emerged factors are follicular fluid granulocyte-macrophage colony stimulating factor (FF-GCSF) and sHLA-G [3].…”

“…would affect fetal development. Suppressor-regulatory T cells (Tsr), which recently gained recognition as involved with pregnancy [3] is an innate immune cell, which is regulated by glucocorticoids and catecholamines [27].…”