Immunity146;s master controller

The innate immune system is the body8217;s main line of defence against bad guys8212;a burglar alarm and a police force all in one. 8216;...

The innate immune system is the body8217;s main line of defence against bad guys8212;a burglar alarm and a police force all in one. 8216;8216;When I was in medical school, the innate immune system didn8217;t get much respect,8217;8217; says Dr Arthur Krieg, whose company, Coley Pharmaceuticals, is working on a cure of cancer. What changed all that was the discovery in the late 8217;90s of 8216;8216;toll-like8217;8217; receptors8212; primitive yet powerful microscopic structures that are at the heart of the immune response.

When the body is invaded by germs, the innate immune system figures out whether it8217;s dealing with bacteria or viruses, then immediately turns on its toll-like receptors. The receptors direct a cascade of defences, telling the body to either eat the germs, kill them or generally make life difficult for them. The system can also warn other parts of the body to buck up their own cellular defences. If none of that works, the innate immune system tries yet another strategy, calling its adaptive counterpart into action. The adaptive immune system is the one most people are familiar with, the system of T cells and B cells that remembers how to fight specific germs the body has been exposed to before. Without the innate system, the adaptive system doesn8217;t know when to work. In other words, the innate system is the master controller that makes immunity possible.

Coley Pharmaceuticals started Phase III trials, in conjunction with Pfizer, last month, injecting lung-cancer patients with synthetic DNA that mimics a virus. 8216;8216;We can trick the body into thinking a cancer is a kind of viral infection,8217;8217; says Krieg. Then there8217;s Coley8217;s approach to HIV/AIDS. Vaccines against the virus haven8217;t worked so far, but Krieg says that in a few small trials, he8217;s used his synthetic DNA to boost their effectiveness, resulting in 8216;8216;a highly significant improvement in the immune response8217;8217;.

Boosting the innate immune system, of course, has risks, chief among them the possibility that doctors might overdo it. Doctors know what happens when the immune system is overactivated: the patient gets an autoimmune disease. Some of the mechanisms the innate immune system uses to fight pathogens8212;particularly inflammation8212;are responsible for a host of health problems of their own.

Of course, 8216;8216;controlling8217;8217; the immune system means being able to turn it down, as well as up. If autoimmune diseases result from an overactive system, the thinking goes, why not just reverse the direction of the system? Take allergies, in which everyday substances are mistaken for pathogens. If doctors could use the innate system to stop the body from reacting in those cases, they could eliminate the illnesses. The treatment comes with its own risk: turning the immune system down too much. Doctors would then have to treat those infections with antibiotics. They8217;d be happy to get far enough down the road to face that problem. Newsweek