**3. The development of systemic inflammatory response in pregnancy**

There is much experimental evidence of a so-called "physiological", controlled SIR during pregnancy. Similarly to the classic inflammatory response, physiological inflammatory response during pregnancy is a reaction to local damage (matrix remodeling, associated with implantation, placentation and angiogenesis in placenta) [92, 93] and foreign invaders (cells, microparticles and soluble factors of placental origin) [94, 95]. Humoral factors, cellular debris and subcellular particles of trophoblast are considered to be the triggers of SIR, but they can also play a role of adjuvants [95, 96]. Cells-effectors of the maternal innate immunity detect fetal products as pathogen/danger images, implementing cell and molecular protection mechanisms against allogeneic material [97]. The gene products inherited from the father can be regarded as exogenous factors, while endogenous factors are gene products, resulting from trauma, ischemia, necrosis or oxidative stress [97]. Also there are some reports on generation of various new antigens due to inflammatory response; they are variations of the "modified own"; of the neoantigens formed as a result of the post-translational proteins modification [98]; and of antigens, mobilized to membrane from cytoplasm and the inner cell compartments interacting with membrane proteins or phospholipids, and acting as images of danger [99]. The enhanced pro-inflammatory background in normal pregnancy is evidenced by an increase of the level of the soluble cell adhesion molecules (sCAM) in blood, indicating the activation of leukocytes (increase of sE-selectin, sVCAM-1, sICAM-1 levels) and endothelial cells [100, 101].
