Vaccines Stage A Comeback

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That kind of fine-tuning necessarily makes the immune system complicated--but to understand the vaccination revolution, you first have to understand the complications. The simplest immune reaction--triggered by a mosquito bite, for example, or an allergen--is inflammation. When the insect bites, the immune system uses cellular troops that have had no special training. Cells called leukocytes, neutrophils and mast cells routinely cruise the bloodstream sniffing for an unfamiliar chemical signature. If they find it, they signal for reinforcements that swarm to kill the invader--the equivalent of an infantry attack.

If the invading bugs are too powerful for this first line of defense, the immune system sends in a second wave of cells. These represent what is known as the innate immune system. Unlike the first wave of defenders, which are crude killing machines, these cells are preprogrammed with biochemical weapons that can target specific types of invaders, including common viruses like influenza and rhinovirus (which causes the common cold).

Even this two-stage counterattack isn't always sufficient, however. When that's the case, it's time for the heavy artillery--the even more specialized cells of the acquired immune response. These cells learn from experience. Once they have been exposed to a virus or bacterium, they will recognize it if it shows up a second time. That's why, for example, you can get chickenpox once but rarely twice.

That much was known decades ago; what drives vaccine researchers today is the effort to understand and manipulate this highly tuned system. The acquired immune response, for example, actually comes in two parts. The first involves antibodies, the molecules produced to match, like a key fitting into a lock, the multiple proteins that coat the surfaces of viruses and bacteria. The more keys on the immune cell's ring, the more likely that the cell can lock onto and destroy a pathogen.

Sometimes, though, the bugs use biochemical trickery to disguise themselves and evade antibodies. The acquired immune system's counterstrategy: so-called antigen-presenting cells, including dendritic cells that latch onto invading bugs and strip them of their chemical camouflage. Thus exposed, the pathogens are prepped for destruction by killer T cells, whose job is to engulf and destroy them. The killer Ts are meanwhile lured to the site of infection in the greatest possible numbers by signaling chemicals known as cytokines, released by the dendritic cells.

The whole process resembles a highly trained military force or, in Nabel's happier analogy, a musical collaboration. And while it works beautifully most of the time, the immune system needs extra help against some diseases. "You literally have an immunologic orchestra," Nabel says, "and if the different sections don't come in in the proper sequence or are not harmonized in the proper way, you may end up with a piece that you're not very happy with."