Early - Warning System Immunity ’ s

A woman is riding an elevator when her fellow passengers start to sneeze. As she wonders what sort of sickness the other riders might be spreading, her immune system swings into action. If the bug being dispersed by the contagious sneezers is one the woman has met before, a battalion of trained immune cells—the foot soldiers of the so-called adaptive immune system—will remember the specifi c invader and clear it within hours. She might never realize she had been infected. But if the virus or bacterium is one that our hapless rider has never wrestled, a different sort of immune response comes to the rescue. This “innate” immune system recognizes generic classes of molecules produced by a variety of disease-causing agents, or pathogens. When such foreign molecules are detected, the innate system triggers an infl ammatory response, in which certain cells of the immune system attempt to wall off the invader and halt its spread. The activity of these cells—and of the chemicals they secrete—precipitates the redness and swelling at sites of injury and accounts for the fever, body aches and other fl ulike symptoms that accompany many infections. The infl ammatory assault, we now know, is initiated by Toll-like receptors (TLRs): an ancient family of proteins that mediate innate immunity in organisms from horseshoe crabs to humans. If TLRs fail, the entire immune system crashes, leaving the body wide open to infection. If they work too hard, however, they can induce disorders marked by chronic, harmful infl ammation, such as arthritis, lupus and even cardiovascular disease. Discovery of TLRs has generated an excitement among immunologists akin to that seen when Christopher Columbus returned from the New World. Scores of researchers are now setting sail to this new land, where they hope to fi nd explanations for many still mysterious aspects of immunity, infection and disorders involving abnormal defensive activity. Study of these receptors, and of the molecular events that unfold after they encounter a pathogen, is already beginning to uncover targets for pharmaceuticals that may enhance the body’s protective activity, bolster vaccines, and treat a range of devastating and potentially deadly disorders.