T cells subdivide into two further categories: helper T cells and killer T cells. Killer T cells, as the name suggests, kill cells that have been invaded by pathogens. Helper T cells help other immune cells act, including helping B cells produce antibodies. Memory T cells remember the details of earlier invaders and are therefore able to coordinate a swift response if the same pathogen shows up again—what is known as adaptive immunity.
Memory T cells are extraordinarily vigilant. I don’t get mumps, because somewhere inside me are memory T cells that have been protecting me from a second attack for more than sixty years. When they identify an invader, they instruct B cells to produce proteins known as antibodies, and these attack the invading organisms. Antibodies are clever things because they recognize and fight off previous invaders quickly if they dare come back. That’s why so many diseases only make you sick once. It is also the process at the heart of vaccination. Vaccination is really a way of inducing the body to produce useful antibodies against a particular scourge without actually making oneself sick.
Microbes have developed various ways of fooling the immune system—by sending out confusing chemical signals, for instance, or by disguising themselves as benign or friendly bacteria. Some infectious agents, like E. coli and salmonella, can trick the immune system into attacking the wrong organisms. There are a lot of human pathogens out there, and much of their existence is devoted to evolving new and cunning ways to get inside us. The wonder isn’t that we get sick sometimes but that we are not sick far more often. In addition, as well as killing invasive cells, the immune system must endeavor to kill our own cells when they misbehave, as when they turn cancerous.
Inflammation is essentially the heat of battle as the body defends itself from damage. Blood vessels in the vicinity of an injury dilate, allowing more blood to flow to the site, bringing with it white blood cells to fight off invaders. That causes the site to swell, increasing the pressure on surrounding nerves, resulting in tenderness. Unlike red blood cells, white blood cells can leave the circulatory system to pass through surrounding tissues, like an army patrol searching through jungle. When they encounter an invader, they fire off attack chemicals called cytokines, which is what makes you feel feverish and ill when your body is battling infection. It’s not the infection that makes you feel dreadful, but your body defending itself. The pus that seeps from a wound is simply dead white cells that have given their lives in defense of you.
Inflammation is a tricky thing. Too much and it destroys neighboring tissues and can result in unnecessary pain, but too little and it fails to stop infection. Faulty inflammation has been linked to all kinds of maladies, from diabetes and Alzheimer’s disease to heart attacks and strokes. “Sometimes,” Michael Kinch, from Washington University in St. Louis, explained to me, “the immune system gets so ramped up that it brings out all its defenses and fires all its missiles in what is known as a cytokine storm. That’s what kills you. Cytokine storms show up again and again in many pandemic diseases, but also in things like extreme allergic reactions to bee stings.”
Much of what happens in the immune system at the cellular level is still very imperfectly understood. Quite a lot is not understood at all. During my visit to Manchester, Davis took me into his lab, where a team of postdoctoral scholars were hunched over computer screens studying images taken from very high-resolution microscopes. A postdoc named Jonathan Worboys showed me something they had only just discovered—rings made of protein scattered across the cell’s surface, like portholes. No one outside this lab had ever seen these rings before.
“They’re clearly formed for a reason,” Davis said, “but we don’t know yet what that reason is. It looks important, but it could be trivial. We just don’t know. It may be four or five years before we really unravel it. It is the kind of thing that makes science exciting and difficult at the same time.”
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If the immune system has a patron saint, it is surely Peter Medawar, who was one of the very greatest of twentieth-century British scientists, as well as possibly the most exotic. The child of a Lebanese father and an English mother, he was born in 1915 in Brazil, where his father had business interests, though when Medawar was a boy the family moved to England. Medawar was tall, good-looking, and athletic. Max Perutz, a contemporary, described him as “vivacious, sociable, debonair, brilliant in conversation, approachable, restless, and intensely ambitious.” Stephen Jay Gould called him “the cleverest man I have ever known.” Although Medawar trained as a zoologist, it was his work with humans during World War II that brought him permanent fame.
In the summer of 1940, Medawar was sitting with his wife in their garden in Oxford enjoying a sunny afternoon when they heard a plane sputtering overhead and looked up to see an RAF Spitfire falling from the sky. It crashed in flames just two hundred yards from their home. The pilot survived but suffered terrible burns. A day or so later, Medawar was presumably surprised to be asked by army doctors if he would come and have a look at the young pilot. Medawar was a zoologist, after all, but he was engaged in research on antibiotics, and there was a chance he might be able to help. It was the beginning of a wonderfully productive relationship that eventually culminated in a Nobel Prize.
The doctors were particularly troubled by the problem of getting skin grafts to take. Whenever skin was taken from one person and grafted onto another, it was accepted at first but then swiftly withered and died. Medawar was immediately gripped by the problem and couldn’t understand why the body rejected something so clearly beneficial. “For all the clinical good-will and perhaps even mortal urgency that accompanies their transplantation, skin homografts are treated as if they were a disease of which their destruction is the cure,” he wrote.
“People thought there was some problem with the surgery, that if surgeons could perfect their technique it would be all right,” says Daniel Davis. But Medawar realized there was something more than that. Whenever he and his colleagues repeated a skin graft, it was always rejected even more quickly the second time. What Medawar subsequently found was that the immune system learns early in life not to attack its own normal, healthy cells. As Davis explained to me, “He discovered that if a mouse was exposed to skin from another mouse when it was very young, then when the mouse grew up, it would be able to accept a skin transplant from that second mouse. In other words, he discovered that at a young age the body learns what is self—what not to attack. You can get a skin transplant from one mouse to another as long as the recipient mouse has been trained in early life not to react to it.” This was the insight that would, years later, win Medawar a Nobel Prize. As David Bainbridge has noted, “Although we take it for granted today, this sudden joining of transplantation and the immune system was a crucial point in medical science. It told us what immunity actually is.”
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