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Deja Vu: Adults' immune systems "remember" microscopic monsters they've never seen before

Probably no human whose age consists of two digits hasn't at one time or another experienced a case of deja vu, the uncanny sense of having been through this (whatever  "this" may be) before.

Well, it turns out that (as the scary narrator of a kitchy sci-fi TV series I inhaled with both nostrils as a kid might say about UFOs and the like), "We're not alone..." Our own immune systems, among whose chief functions is to fight off invading pathogens, also entertain "memories" of infectous microbes they've never, ever encountered. And that's a lucky thing.

A human has only 20,000 or so genes, so it's tough to imagine just how our immune systems are able to recognize potentially billions of differently shaped microbial body parts (or "epitopes" in immune-speak). Stanford immunologist Mark Davis, PhD, tore the cover off of immunology in the early 1980s by solving that riddle.

Now, in a just published study in Immunity, Davis and his team have used an advanced technique developed in his lab in the 1990s to  show that a surprising percentage of adult humans' workhorse immune cells targeting one or another microbial epitope are poised to pounce on the particular epitope they target (and the bug it rode in with) despite having never come across it before. This hypervigilant configuration, called the "memory" state, was previously supposed to be limited to immune cells that have previously had a run-in with the epitope of interest.

Davis think's he's got the dirt on what's behind the phenomenon: Dirt. He reasons that the kind of immune cells in question have more flexibility than has been thought, so each of them can "cross-react" to a small set of similarly but not identically shaped "lookalike" epitopes it's never experienced. Our daily exposures to ubiquitous, mostly harmless micro-organisms that dwell in dirt, on doorknobs, and in our diets gradually produces an aggregate immune "memory" of not only these microbes' body parts, but those of other bugs as well - including some nasty ones like HIV (the virus that causes AIDS), herpesvirus, and more.

Because cells in the "memory" configuration can react much, much faster to an infectious pathogen than "naive" cells targeting the exact same pathogen, this eerie foreknowledge can spell the difference between life and death.

But this immune memory still depends on having been exposed to something. In the study, the immune cells in blood from newborns' umbilical cords showed no "memory" of anything at all.

As I wrote in my release on the new findings:

[This discovery] could explain why young children are so much more vulnerable to infectious diseases than adults. Moreover, the findings suggest a possible reason why vaccination against a single pathogen, measles, appears to have reduced overall mortality among African children more than can be attributed to the drop in measles deaths alone.

"It may even provide an evolutionary clue about why kids eat dirt," Davis told me.

Previously: Immunology escapes from the mouse trap,  Age-related drop in immune responsiveness may be reversible and Common genetic Alzheimer's risk factor disrupts healthy older women's brain function, but not men's
Photo by Damian Gadal

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