For instance, the imprintedIgf2gene acts within the labyrinth to regulate the diffusion exchange characteristics of the mouse placenta

For instance, the imprintedIgf2gene acts within the labyrinth to regulate the diffusion exchange characteristics of the mouse placenta. of natures great mysteries. Since the fetus and its placenta are derived from both mother and father this organ is usually in essence a tissue transplant. In an uncomplicated pregnancy the placenta is usually a semi-allograft in which the paternally derived antigens are incompatible with the maternal immune system. In contrast, in a donor oocyte or surrogate pregnancy the placenta may be a full allograft which is usually genetically unrelated to Maropitant the host mother. The immune paradox of pregnancy, in which the mother must tolerate the placenta and fetus yet not succumb to contamination, was first elaborated by Sir Peter Medawar more than half a century ago. However, Mouse monoclonal to Tyro3 how much is actually known about how maternal tolerance is usually achieved and how mother and fetus survive what should be an immune discord? The workshop focused on three specific questions: 1) Are uterine natural killer (uNK) cells required for human pregnancy; 2) Where and what is the maternalfetal interface: uterus, lymph, maternal blood?; 3) Antigen specific tolerance: can we generate tolerance – are there antigens to do this? == 1.2. Summary == The Chairpersons opened the workshop by briefly presenting a case history of an abdominal pregnancy in a woman after total hysterectomy. Although 22 such pregnancies had been previously reported, this was the first in which the fetus was live-born. This appropriately launched the first question in the light of this case are uNK cells essential for pregnancy? Anne Croy examined immune deficient mouse strains with very few to no Maropitant uNK cells but successful gestation, indicating that uNK cells are not essential for murine pregnancy. The benefit of uNK cells, defined by murine studies, lies in protection of maternal and fetal hearts from abnormal compensation to the elevated cardiovascular demands of pregnancy. Judith Bulmer indicated that while the role of uNK cells in normal pregnancy has been intensively researched, decidual macrophages and T lymphocytes are receiving much less attention. Uterine NK cells potentially interact directly with extravillous trophoblast (EVT). In addition they secrete many cytokines, angiogenic growth factors and proteases, levels of which differ with gestational Maropitant age. In tubal pregnancy EVT invades the fallopian tube wall and arteries, ultimately resulting in tube rupture/haemorrhage. Tubal implantation sites contain T cells and macrophages but, unless there is decidualisation Maropitant of tubal mucosa, uNK cells are absent. In placenta accreta, decidua (and uNK cells) Maropitant is at least focally absent but trophoblast invades myometrium and arteries. Uterine NK cells are present in ectopic decidua in pregnancy and in decidualised tissue. Successful extra-uterine pregnancy may reflect areas of extra-uterine decidualisation with uNK cells in ectopic decidua interacting with EVT. Alternatively, there is likely to be redundancy within the system and other cell types may fulfill uNK cell function at extra-uterine sites. Peter Parham explained how interactions of killer cell immunoglobulin-like receptors (KIR) with human leukocyte antigen (HLA) class I molecules regulate these functions and are specific to simian primates, where co-evolution of receptors with ligands is usually evident. Emerging in hominoids as superior KIR ligands, the C1 and C2 epitopes of HLA-C are the only variable epitopes on trophoblast cells and thus able to bind uNK cell KIR. The combination of fetal C2 and maternalKIR Ahaplotypes correlates with pregnancy disorders that cause death, non-competitive offspring, and barrenness. The selection pressure they impose is usually writ in the impressive inverse correlation between C2 andKIR Afrequencies worldwide. Human survival has clearly benefited from your contribution of uNK cells. This does not rule out rare occurrences of human reproduction without uNK cell function, but suggests it would not be a competitive evolutionary strategy in the long run. In some circumstances dramatic change can be effective, as illustrated in gibbons that lost HLA-C, HLA-G and all but one KIR. Such simultaneous losses also point to the importance of uNK cell receptors and ligands in human reproduction. Ted Golos explained how CD56+/perforin+uNK cells in the rhesus monkey have morphological heterogeneity, including small.