A man came one day to the Royal Perth Hospital in Australia saying he was tired. He had been tired for two years, and now, in the summer of 1980, he decided it was time to find out what was wrong with him. His health wasn’t perfect, but it wasn’t terrible either. He had been a heavy smoker in his teens and twenties, but at forty-four, his only indulgence was a glass of white wine each night.
His doctor could feel through his skin that his liver was swollen. On an ultrasound image, two of its three lobes loomed too large. Yet, there were no signs of the kinds of trouble the doctor would expect to find, such as a tumor or cirrhosis. It was when the doctor got the report on the man’s stool that he realized what had happened: the stool was loaded with the spiny eggs of Schistosoma mansoni—blood flukes found only in Africa and Latin America.
The doctor had the man walk him through his life. It had started roughly. He had been born in Poland in 1936. The Soviet army had taken his family during the Second World War and held them in a Siberian prison camp. Toward the end of the war they had escaped, traveling through Afghanistan and Persia, finally ending up in a refugee camp in East Africa. For six years, savannas were his playgrounds, until 1950, when his family emigrated to Australia. He had remained there for the rest of his life.
The math is simple enough, yet hard to believe: the only time in the man’s life when he was anywhere near Schistosoma mansoni was in the late 1940s. When he swam and bathed in Tanzanian lakes, at least one pair of flukes had invaded his skin and journeyed into his veins; they had traveled with him to Australia and started a new life with him, and male and female flukes had gone on living, quietly entwined and pumping out eggs, for over thirty years.
What makes the longevity of the blood flukes all the more impressive is that they attained it under perpetual menace and attack. Lankester was under the impression that once inside a host, a parasite was home free. It needed to do nothing more than drink up the food that bathed it, and could in fact do nothing more. But he wrote his essay “Degeneration” in 1879, when immunology, the science of the body’s defenses, was still little better than alchemy. Physicians knew that they could protect people from smallpox by injecting a bit of a pox sore into them, but they had no idea how they were actually saving lives. Within a few years of Lankester’s essay, scientists would discover predatory cells roving our bodies and devouring bacteria, and immunology was born.
To sum up what scientists have learned since then about the immune system is like trying to reproduce the Sistine Chapel in crayon. It is orchestral in its complexity, with a huge diversity of cells, all communicating among each other with a dictionary’s worth of signals, along with dozens of kinds of molecules designed to help the cells decide what should be destroyed and what should be spared. It acts like a blood-borne brain. But here, at any rate, is a brief survey of the most important ways in which our bodies kill parasites.
The immune system attacks an intruder—bacteria crawling into a cut, for instance—in a succession of waves. One of the first waves is a collection of molecules called complement. When complement molecules hit the surface of bacteria, they latch on and change their shape so that they can snag other passing complement molecules. Gradually the molecules build up on the surface. They assemble themselves into tools of destruction, like drills that can open a hole in the bacteria’s membranes. They also act like beacons, making the bacteria more visible to immune cells. Complement molecules also land on our own cells, but they do no harm. Our cells are coated with molecules that can clamp onto a complement molecule and cut it apart.
Also arriving early at the cut are wandering immune cells, the most important of which are the macrophages. They have some crude ways of recognizing bacteria if they happen to bump into them, and they can suck the invaders into their cores and slowly digest them. At the same time, the macrophages also release signals that bring the rest of the immune system’s attention to the site. Some of these signals make the infection swell up by loosening the neighboring blood vessel walls. That lets other immune cells and molecules flood into the tissue. The signaling molecules released by the macrophages also latch onto immune cells that happen to be flowing by in nearby blood vessels. They lead the cells through the vessel wall and to the infection, like a boy dragging his mother by the hand down a toy store aisle.
With enough time, the immune system can organize a new wave of attack, using much more sophisticated cells: B and T cells. Most of our cells come with a standard issue of receptors on their surface. One red blood cell looks pretty much like the next. But when B and T cells form, they shuffle the genes that make the receptors on their surface. The cells use the altered genes to build new receptors with shapes not found in any other immune cell. This shuffling can produce hundreds of billions of different shapes, so that each new B or T cell is as distinct as a human face.
Because they are so diverse, B and T cells can grab a huge range of molecules, including the ones on the surface of invaders. (Foreign molecules that trigger an immune response are called antigens.) First, though, the cells have to get a proper introduction to the antigens. This job is accomplished by macrophages and other immune cells. As they engulf bacteria or their cast-off fragments the immune cells cut them up into little pieces. They then bring these antigens to their surface, displaying them in a special cup (the major histocompatibility complex, or MHC for short). Parading these conquests, the immune cells travel into the lymph nodes. There they bump into T cells. If a T cell has the right kind of receptor, it can lock onto the antigens displayed by a macrophage. As soon as it recognizes the antigen, the T cells start multiplying quickly into a battalion of identical cells, all equipped with the same receptor.
These T cells can take one of three forms, each of which kills the invaders in a different style. Sometimes they become killer T cells, which search the body for cells that have been invaded by pathogens. They recognize infected cells, thanks again to MHC. Like macrophages, most cells in the human body can display antigens on MHC receptors of their own. If the killer T cell recognizes these signs of trouble, it commands an infected cell to commit suicide. The parasite within dies along with it.
In other cases, activated T cells set out to coordinate other immune cells to do a better job of killing. Sometimes they help by becoming inflammatory T cells. These cells crawl their way to the macrophages that are struggling to fight the rising tide of bacteria. They lock onto the antigen displayed on the macrophage’s MHC. That locking acts like a trigger, turning the macrophage into a more violent killer, spraying more poisons. At the same time, the inflammatory T cells help make the cut swell far more than the macrophages can manage on their own. The inflammatory T cells also kill off tired old macrophages and spur the production of new ones to devour their elder cousins. They’re like battle-hungry generals: they’re good to have around in a war but can’t be allowed to get out of control. Too much inflammation, too many poisons created by macrophages, and the immune system will start destroying the body itself.
In the third form that T cells take, they help B cells make antibodies. B cells have the same diversity of surface molecules as T cells, so they also have the potential to snag onto billions of different kinds of antigens. After a B cell has latched onto a fragment, a helper T cell may come along and hook onto it at the same time. In these unions, the T cell can give the B cell signals to start making antibodies. Antibodies are a kind of free-floating version of a B cell receptor, also able to clasp onto an antigen from an invader.