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Adult humans harbor lots of risky autoreactive immune cells, study finds

dangerIf a new study published in Immunity is on the mark, the question immunologists may start asking themselves will be not "Why do some people get autoimmune disease?" but "Why doesn't everybody get it?"

The study, by pioneering Stanford immunologist Mark Davis, PhD, and colleagues, found that vast numbers of self-reactive immune cells remain in circulation well into adulthood, upending a long-established consensus among immunologist that these self-reactive immune cells are weeded out early in life in an organ called the thymus.

A particular type of immune cell, called “killer T cells,” is particularly adept at attacking cells showing signs of harboring viruses or of becoming cancerous. As I wrote in my news release about Davis's study:

[The human immune system generates] a formidable repertoire of such cells, collectively capable of recognizing and distinguishing between a vast array of different antigens - the biochemical bits that mark pathogens or cancerous cells (as well as healthy cells) for immune detection. For this reason, pathogenic invaders and cancerous cells seldom get away with their nefarious plans.

Trouble is, I wrote:

[This repertoire includes] not only immune cells that can become appropriately aroused by any of the billions of different antigens characteristic of pathogens or tumors, but also immune cells whose activation could be triggered by myriad antigens in the body’s healthy tissues. This does happen on occasion, giving rise to autoimmune disease. But it happens among few enough people and, mostly, late enough in life that it seems obvious that something is keeping it from happening to the rest of us from day one.

It's been previously thought that the human body solves this problem by eliminating all the self-reactive T cells during our early years via a mysterious select-and-delete operation performed in a mysterious gland called the thymus that's nestled between your heart and your breastbone. Sometime in or near your early teens, the thymus mysteriously begins to shrink, eventually withering and largely turning to useless fat. (Is that mysterious enough for you? It sure creeps me out.)

But Davis and his team used some sophisticated technology - some of it originally invented by Davis, some of it by Stanford bioengineering professor and fellow study co-author Stephen Quake, PhD - to show that, contrary to prevailing dogma, tons of self-reactive killer T-cells remain in circulation well into adulthood. Then the scientists proceeded to explore possible reasons why the immune system keeps these risky cells around (it boils down to: just in case a pathogen from Mars comes along and we need to throw the kitchen sink at it) and why (at least most of the time) they leave our healthy tissues alone: A still-to-be-fully-elucidated set of molecular mechanisms keeps these self-reactive cells locked in the biochemical equivalent of parking gear, shifting out of which requires unambiguous signs of an actual pathogen's presence: bits of debris from a bacterial cell wall, or stretches of characteristically viral DNA.

That's our immune system, folks. Complicated, mysterious, and yet somehow incredibly efficient. You really don't want to leave home - or even the womb - without it.

Previously: In human defenses against disease, environment beats heredity, study of twins shows, Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology's Holy Grail, In men, a high testosterone count can mean a low immune response and Deja vu: Adults' immune systems "remember" microscopic monsters they've never seen before
Photo by Frederic Bisson

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