In the context of NK-cell inhibitory and activating receptors and maternal arterial invasion, explain the cause of (A) pre-eclampsia and (B) obstructed labor
Base your response on a pregnancy involving a fetus who has inherited a C2 epitope from the father but whose mother is homozygous for C1.
What will be an ideal response?
A. If a mother is homozygous for the KIR A haplotype, she expresses KIR2DL1 (an inhibitory NK-cell receptor) that binds to the C2 epitope of HLA-C on extravillous trophoblast cells. She does not, however, express KIR2DS1 (an activating NK-cell receptor) that uses the same C2 epitope ligand as KIR2DL1. In this combination, uterine NK cells do not receive sufficient activation to secrete the cytokines and growth factors that are required to adequately promote new blood vessel formation (angiogenesis). The result is shallow trophoblast invasion of the spiral arteries during implantation, which can result in an increased risk of pre-eclampsia in which the baby does not receive sufficient nutrients and the mother's blood pressure rises to dangerously high levels that could lead to hemorrhage.
B. If a mother is homozygous for the KIR B haplotype, she expresses KIR2DS1, which counterbalances the effect of inhibitory C2-specific receptors. In this combination, uterine NK cells are activated in a manner that favors deep placental invasion and over-nourishment during pregnancy. Elevated birth weight can lead to an obstructed labor.
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