The mother’s immune system learns how to protect the embryo instead of attacking it as foreign material.

The immune system is blind; it has no brain on its own.  It is programmed to identify and fight foreign substances; that it does very well.  How, then, can it identify a firstborn implanted embryo as a feature that needs protection instead of attack?  The embryo contains antigens from the father, and its own unique genetic blend, that should rouse the mother’s immune system to fight it as an invader.

Specific proteins in specific immune cells are there to help.  They “learn” that pregnancy is a good thing, and they remember it when the next baby is on the way.  A paper in Nature described new findings about this elaborate process.

Pregnancy is an intricately orchestrated process where immune effector cells with fetal specificity are selectively silenced. This requires the sustained expansion of immune-suppressive maternalFOXP3+ regulatory T cells (Treg cells), because even transient partial ablation triggers fetal-specific effector T-cell activation and pregnancy loss. .… Here we show that pregnancy selectively stimulates the accumulation of maternal FOXP3+ CD4 cells with fetal specificity using tetramer-based enrichment that allows the identification of rare endogenous T cells. Interestingly, after delivery, fetal-specific Treg cells persist at elevated levels, maintain tolerance to pre-existing fetal antigen, and rapidly re-accumulate during subsequent pregnancy.… Thus, pregnancy imprints FOXP3+ CD4cells that sustain protective regulatory memory to fetal antigen.   (Rowe et al., “Pregnancy imprints regulatory memory that sustains anergy to fetal antigen,” Nature 490, 4 Oct 2012, pp. 102–106, doi:10.1038/nature11462.)

In the same issue of Nature, Alexander G. Betz described the challenge a mother’s immune system faces:

Pregnancy poses a conundrum for the immune systems of placental mammals. A pregnant female’s immune system has to defend both mother and fetus from pathogens, while at the same time tolerating the fetus, which contains antigens that the maternal immune system recognizes as foreign because they are the products of genes inherited from the father. On page 102 of this issue, Rowe et al. demonstrate that, during pregnancy, immune cells called regulatory T cells that recognize these paternal antigens proliferate in the mother and specifically suppress the maternal immune response against the fetus. Furthermore, the authors show that a pool of these cells remains long after delivery, facilitating tolerance in subsequent pregnancies.  (Alexander G. Betz, “Immunology: Tolerating pregnancy,”Nature 490, 4 Oct 2012, pp. 47–48, doi:10.1038/490047a.)….

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