Immunity system complexity: protecting pregnancy (Introduction)

by David Turell , Tuesday, November 14, 2023, 22:38 (374 days ago) @ David Turell

The fetus is a foreign body, but not to the immune system:

https://www.quantamagazine.org/

"The study showed how the placenta — the embryonic organ that connects offspring and mother — uses a molecular trick to feign illness. By pretending it’s under viral attack, it keeps the immune system running at a gentle, steady pace to protect the enclosed fetus from viruses that slip past the mom’s immune defenses.

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"Because antiviral immune weapons can destroy tissues, cells typically turn them on only when there’s an active threat like an infection, Kagan said. Then, once the infection clears, those weapons are turned off as quickly as possible.

"But the placenta breaks these rules, according to the new research. Somehow, it turns on defenses before they are necessary and then leaves them on without harming itself or the fetus.

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"It took years for Totary-Jain and her team to zero in on an answer: The placental cells had crafted a viral look-alike, using RNA harvested from their own genomes, to dupe their immune sensors.

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"But the data implicating Alus was too compelling to ignore. After years of careful experiments, Totary-Jain’s team showed that in the placenta, transcripts of Alu repeats formed snippets of double-stranded RNA — a molecular silhouette our cells recognize as viral in origin. Sensing the fake virus, the cell responded by producing interferon lambda.

“The cell is effectively dressing up as an infectious agent,” Kagan said. “The result is that it convinces itself that it’s infected, and then operates as such.”

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"...cells cry “Virus!” at their own risk. In most tissues, Alu sequences are highly suppressed so that they never get a chance to mimic a viral attack. And yet that is the exact scenario the placenta seems to create on purpose. How does it balance the health of the growing embryo with a potentially risky immune response?

"In experiments with mice, Totary-Jain’s team found that the placenta’s double-stranded RNAs and ensuing immune response didn’t seem to hurt the developing embryos. Instead they protected the embryos from Zika virus infection. The placental cells were able to toe the line — conferring protection on the embryos without cuing a self-destructive immune response — because they called in the gentler defenses of interferon lambda.

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"Typically the first responders to double-stranded Alu RNA escapees are type I and type II interferons, which quickly recruit destructive immune cells to the site of an infection, leading to tissue damage and even autoimmune disease. Interferon lambda, on the other hand, is a type III interferon. It acts locally by communicating only with cells within the tissue, generating a milder immune response — one that can be sustained long term in the placenta.

"How placental cells manage to activate only interferon lambda, keeping the immune response simmering but never boiling over, is still a mystery. But Totary-Jain has an idea about why placental cells evolved this trick that other cells seemingly avoid: Since the placenta is discarded at birth, perhaps it can afford to take immune risks that other tissues can’t.

"The findings reveal a new strategy the placenta has for protecting the fetus, apart from mom’s immune system. Since the mother’s immune response is dampened during pregnancy to prevent attacks on the genetically distinct embryonic cells, the placenta has had to develop extra defenses for the growing baby it supports.

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"It’s possible, then, that this kind of immune trickery is more common than anyone thought. By studying how the immune system seems to break its own rules, scientists can better define what the rules are in the first place.

Comment: a perfect example of irreducible complexity. Attempting to evolve this step by step is impossible. There are too many moving parts at play to be placed in motion all at once. Managing the accommodation of mother's pelvis to enlarging fetal skull size is another issue.