The human fetus is a natural allograft, at risk of T cell-dependent alloimmune rejection the presence of two fetal-maternal immune interfaces in human pregnancy pregnancy, interface I comprises a localized tissue interaction in the decidua between maternal NK cells and invasive, fetal extravillous cytotrophoblast. The syncytiotrophoblast at the surface of the hemochorial placenta forms interface II in contact with maternal blood. Interface I regresses in the second half of pregnancy with loss of the invasive trophoblast (3) and the associated decidual lymphocytes (4). Interface II is activated with onset of the uteroplacental circulation at 8-9 wk (5) and enlarges with placental growth to become the main maternal-fetal immune interface after 20 wk of pregnancy. in later pregnancy the dominant immune interaction at interface II involves the innate rather than the adaptive systems and is characterized by a mild systemic inflammatory state in activation of circulating leukocytes (6), the associated acute phase response and the parallel endothelial activation (9).
We have shown that pre-eclampsia is associated with more exaggerated systemic inflammatory changes (6) and argued that pre-eclampsia is what happens when the response is so intense as to provoke the features of the disorder
Pre-eclampsia the second half of pregnancy, comprising variable combinations of signs of which hypertension and proteinuria including dysfunction of clotting and of the liver. to crises which can be fatal include convulsions and the acute hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome,3 which is characterized by disseminated intravascular coagulation, acute hemolysis, and liver damage cause of the inflammatory response is not known that alloimmune reactivity to the fetoplacental unit (11) is possible in relation to murine rather than human pregnancy equivalent. Inflammatory responses are not Ag specific and our current hypothesis is that one or more factors derived from the placenta are the stimuli, which does not depend on, or evolve into, Ag-specific immunity. The relevant issues are the intensity and quality of the maternal inflammatory response and its relation to the maternal syndrome of pre-eclampsia excessive inflammatory response of pre-eclampsia: TNF-_, IL-12, IL-18, and IFN-_.Shwartzman reaction, which is a lethal response to endotoxin after a prior priming injection.
Pregnant animals are uniquely sensitive to the Shwartzman Reaction of endotoxin is not needed (
12). A notable feature of the HELLP syndrome is its hyperacute presentation in some women which matches the acute time course of the Shwartzman response. a positive feedback loop in which activated monocytes secrete IL-12 and IL-18 that stimulate lymphocytes to produce IFN-_, which magnifies further the degree of activation of the monocytes
14). Hepatic necrosis, which is a typical consequence of the HELLP syndrome, occurs in a murine variant of the Shwartzman reaction (15), in which it has been shown that IL-18, IL-12, IFN-_ and TNF-_ all contribute to the experimental pathology.
Totally prevented by prior administration of anti-IL-18 but is only partially ameliorated by anti-IFN-_ or anti-TNF-_ in human pregnancy, circulating monocytes are primed to produce IL-12 may indicate that a human equivalent to the Priming
Candidate stimulants for the systemic inflammatory response of pregnancy include circulating cytokines or antiangiogenic factors (18), products of oxidative stress (19), or subcellular debris shed from the syncytial surface of the placenta in human hemochorial placentation, the outermost layer of the placenta, the syncytiotrophoblast, is in direct contact with maternal blood. microparticulate
Debris from the placenta will be shed into the maternal circulation and could interact with both maternal leukocytes and vascular endothelium. Furthermore, the syncytiotrophoblast is both class I and class II MHC negative and will therefore not provoke classical T cell allograft responses. of flow cytometric measurement of the binding of syncytiotrophoblast membrane Ags to peripheral blood monocytes.
Such binding occurred in normal pregnancy and, if so, at what stages of pregnancy it could be detected and if pre-eclampsia changed the degree of binding the role of syncytiotrophoblast membrane microparticles (STBM) that are shed can stimulate the production of proinflammatory cytokines.
Purpose, microparticles were prepared from placentas from healthy pregnancies, both by the standard mechanical method (mSTBM) cotyledons (pSTBM), which may better represent the particles shed in vivo, and used in coculture experiments with PBMCs.
The systemic inflammatory
Response of pregnancy and pre-eclampsia, its evolution during normal pregnancy the changes that are associated with pre-eclampsia.
Cytokines TNF-_, IL-12, IL-18, and IFN-_ importance in the Shwartzman reaction how early during normal pregnancy circulating STBMs can be detected, whether they circulate in maternal blood bound to PBMCs, specifically monocytes, and whether they stimulate secretion of inflammatory cytokines from PBMCs when cultured ex vivo an enhanced inflammatory response can be elicited from PBMCs from the first trimester onwards, that it is characterized by suppression of lymphocyte production of IFN-_ and that this suppression is partially released in pre-eclampsia with enhanced IL-18 production. STBMs are proinflammatory in culture and could contribute to the systemic inflammatory response that we observe, both in normal pregnancy and in pre-eclampsia.