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Stanford Medicine Scope -April 4th, 2016 - by Bruce Goldman
Many of ur-psychoanalyst Sigmund Freud’s pet concepts have long since been debunked, and debunked again, under a steady onslaught of neuroscience and pharmacology. But the man knew how to turn a phrase.
In his classic treatise Civilization and Its Discontents, Freud coined a wonderful term- “the return of the repressed” – to denote the resurfacing of primitive urges long stifled, but never annihilated, in the service of sustaining sophisticated societal stability. Should those urges resurface, you’ve got the makings of a horror flick.
If ever a disorder was completely nailed by the phrase “return of the repressed,” it’s the one called shingles. (The technical name is herpes zoster.)
Shingles is no fun, and way too common. “Every second person gets it with age,” says Stanford immunologist Jorg Goronzy, MD. It’s also (about half the time, anyway) preventable by an available vaccine. “Everybody older than 50 should have the vaccination,” according to Goronzy.
Shingles results from the failure of aging immune systems to prevent the re-activation of the chickenpox virus, varicella zoster, which has ensconced itself in the DNA of sensory nerve cells in anyone who’s ever had chickenpox. There’s nothing the slumbering virus would rather do than wake up and make trouble; but whenever it tries to do that, the healthy immune system slaps it down.
However, our immune systems weaken with advancing age. When this reaches a critical point, the erstwhile latent virus can reconstitute itself and travel down these long nerve pathways to produce an excruciating rash on whatever patch of skin the resurgent pathogen manages to randomly reach.
The mere brushing of a bathrobe or a bedsheet against an affected area can elicit howls of pain. Shingles can cause loss of vision.
A new study led by Goronzy and featured in Science Translational Medicine provides evidence as to why a single shot is insufficient for roughly half of those vaccinated, and suggests why, for them, booster shots might make vaccination more effective.
The immune response to viral infection relies on a set of circulating soldiers known as T cells. When a T cell senses an invading pathogen’s presence, it goes on offense. Stated loosely, every mature T cell is dedicated to responding to a particular biochemical shape (or, in science-ese, “antigen“). But any given T cell proliferates and mounts an attack against only pathogens bearing the antigen to whose shape the T cell is attuned. Most pathogens sport more than a single antigen, so a variety of T cells collectively targeting diverse antigens of the same pathogen is desirable.
Goronzy’s team found that older people differ among one another in how many different varieties of herpes-zoster-virus-specific T cells they have, and how many of those varieties (and which ones, and how well) a single vaccination dose actually activates. That, in turn, may determine the quality of the immune response to a resurgence of the virus.
As Freud himself put it: “Every normal person, in fact, is only normal on the average.”
This new knowledge could spawn a blood test that could helps physicians figure out who belongs to the half of the population that would benefit from booster shots of the shingles vaccine.
