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February 2nd, 2016 - Stanford Medicine Scope - by Bruce Goldman

Even perfectly healthy older people don’t always remember names as quickly as they did when they were younger. So what. They also don’t walk as fast. Big deal.

A bigger deal: Older immune systems don’t respond as quickly or as well to invasions by pathogens. That’s in large part because they fail to remember previous encounters with pathogens (or their defanged doppelgängers, which we call vaccines). Why do they forget? Stanford immunologist Jorg Goronzy, MD, may have a handle on part of the reason.

In a study published in Cell Reports, Goronzy and his colleagues have shown that immune cells of a particular type are more likely to be marked, in older people, by a surface protein that sparks apoptosis, or cellular suicide. As a result, the immune system’s memory of pathogens or vaccinations of yore gets cloudy, leaving the door open to a repeat attack by intruders that a more adept immune system would have summarily squelched.

A healthy immune system bulks up vigorously in response to pathogens or vaccines. Different types of immune cells that are skilled at recognizing and/or warring with the foreign body start to multiply and morph. Many of these cells effectively become front-line warriors, throwing themselves into battle against the invading pathogen (or its harmless vaccine lookalike). Others are more like archers lobbing darts that can knock off the bad guys while sparing innocent bystanders (the body’s own tissues). Still others, known as CD4 cells, coordinate the whole counterattack, sending chemical signals to other cells, or rubbing up against them at close range to whisper secret instructions.

Once the tide of the battle has turned, the numbers of these valiant troops drop back down to peacetime levels — they die off. That’s as it should be. Milling masses of surplus immune warrior cells with time on their hands can cause problems, in the form of autoimmune or inflammatory disease. (Heck, even the U.S. Constitution — see Article I, Section 8, Clause 12 — expressly prohibits appropriation of funds for a standing army for periods of longer than two years.)

Still, an elite intelligence corps of long-lived CD4 cells remains in uniform and on patrol long after a disease (or the “ouchie” of a vaccine) subsides, ready to blow the whistle on any attempted re-entry by marauding pathogens. The persistence of these “memory” CD4 cells – sometimes for many decades after their original exposure – are why we resist so many diseases we’ve had before.

But by comparing immune cells from younger versus older donors, Goronzy and his teammates found aging people’s immune “memory” cells are much likelier than young peoples’ to carry a surface protein that exhausts energy supplies within those cells, tripping off a suicide signal inside the cells. That ends their lives, leaving older people depleted of their veteran immune lookouts.

Exactly why this happens, or what would result from reversing it, isn’t fully clear yet. But identifying a problem is the first step toward fixing it.

Originally published at Stanford Medicine Scope Blog