2011 medicine Nobel goes to immunology researchers

Medical researchers recognized for work on innate, adaptive defenses

Three scientists who deciphered key aspects of the body’s defense against infection have won the 2011 Nobel Prize in Physiology or Medicine.

Bruce Beutler of the University of Texas Southwestern Medical Center in Dallas, and Jules Hoffmann of the Molecular and Cellular Biology Institute in Strasbourg, France, will share half of the $1.5 million award for discovering the role of toll-like receptor proteins in immune reactions. Beutler and Hoffmann concentrated on innate immunity, a primitive branch of the body’s defense system.

The other half of the prize goes to the late Ralph Steinman of Rockefeller University in New York City for his discovery of immune sensors called dendritic cells, which bring pathogens to the attention of immune enforcers called T cells. His findings established dendritic cells as a link between innate and adaptive immunity, in which the body develops a memory specific to a given pathogen.

Steinman died on September 30. Nobel rules forbid awarding the honors posthumously, but, given the timing, the committee says Steinman’s award will stand.

The immune system primarily provides its host with a defense against infectious agents. Some scientists are now trying to harness the immune system’s defenses to attack cancer. Others are looking to shut down runaway immunity in inflammatory diseases. The findings honored by the 2011 award have improved scientists’ chances of achieving these goals, the Nobel Committee said.

Toll-like receptors are key players in innate immunity, the front line of defense against invaders. Since the body endures a nonstop assault by pathogens at the microscopic level, it requires constant surveillance to determine whether a substance that a cell encounters is friend or foe. Toll-like receptors are central to this task.

Toll-like receptors “recognize different components shared by many microbes or viruses; they don’t need to be very specific,” says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. “They deliver the first foot in the battle.”

In the 1990s, Hoffmann was studying fruit flies when he found that mutations in a gene called Toll left them unable to fend off bacterial or fungal infections. Later that decade, Beutler discovered that the protein encoded by mammalian versions of the gene served as a receptor on cells. This “toll-like receptor” acted like a trip wire, he noted, alerting first-line immune defenses to a foreign bacterial compound and triggering inflammation.

Some pathogens evade detection by the innate immune forces; that’s where the more specialized adaptive immune system comes into play. Steinman had previously discovered a cell called a dendritic cell, and ultimately showed that it could sense innate immune responses and trigger an adaptive immune reaction — a handoff that provided highly specialized protection. “This is a situation where these three investigators complemented each other very well,” Fauci says.

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