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Immune cells show long-term memory

Almost a century after exposure to the 1918 Spanish flu, survivors’ white blood cells still recognize the virus

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12:23pm, August 17, 2008
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Even after 90 years, the immune system doesn’t forget the face of a mass-murderer. A new study shows that survivors of the 1918 Spanish flu pandemic still have immune cells that remember the culprit virus.

Such long-lived immunity was thought to be impossible without periodic exposure to the microbe that stimulated the immune system in the first place. But a study published in advance online August 17 and slated for an upcoming issue of Nature reveals that immunity to a virus can last nearly a century.

“This is a really extraordinary finding,” says Peter Palese, a virologist at Mount Sinai School of Medicine in New York City who was not involved in the study. “It’s like immunological archaeology.”

Previous research showed that elderly people have antibodies that can recognize the 1918 flu virus, but that those antibodies usually also latch on to more recent viruses of the same subtype as the Spanish flu. The new study demonstrates that the immune system retains a specific memory only for the 1918 virus, which killed more than 20 million people worldwide.

Researchers led by viral immunologist James Crowe of VanderbiltMedicalCenter in Nashville, Tenn., found a type of immune memory cell called B cells in the blood of elderly people who had lived through the 1918 Spanish flu pandemic. B cells are white blood cells that make antibodies against specific features of the proteins of an invading microbe.

In the pandemic survivors, about one in every 4.6 million B cells made antibodies that attack the 1918 virus but don’t latch on to more recent flu viruses that resemble the Spanish flu. That results offer evidence that the immune system remembers a virus for decades without being stimulated by reexposure, Palese says.

Although the 1918 pandemic was particularly virulent, the new study suggests the immune system can probably sustain a lifetime’s worth of defense against less deadly diseases as well, Palese says. And good vaccines should produce similar longevity in the immune response, possibly eliminating the need for frequent booster shots, he says.

Antibodies produced by the pandemic survivors are some of the most potent antibodies ever described, says Crowe. Mice given the antibodies and also infected with the 1918 virus survived.

“This is entirely counter to everyone’s intuition — that elderly people would have such potent antibodies,” Crowe says. Aging typically reduces a person’s ability to build antibodies and develop immunity to diseases, so it was a surprise to find that the elderly survivors of the Spanish flu could still mount such a vigorous defense against the virus.

Should the 1918 virus reappear, antibodies from the survivors might be used as a therapy to treat infected people, Crowe suggests. He and his colleagues produce the antibodies from cell cultures of the survivors’ B cells to prevent the need to keep drawing blood from the survivors.

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