A host’s immune system notices the arrival of a tapeworm egg and builds antibodies to it, but by the time it has become organized for an attack, the egg has disappeared; the larva has escaped and formed a cyst for itself. Immune cells crowd around the cyst and build an outer wall of collagen, and yet they can do nothing more. While the cyst takes in food it also releases over a dozen kinds of molecules, each of which stuns the immune system. Complement settles onto the cyst, but the tapeworm releases a chemical that binds to the molecule and stops it from combining into membrane-penetrating drills. The immune cells blast the cyst with highly reactive molecules that can kill tissue, but the tapeworm releases other chemicals that disarm them. And like Leishmania, the tapeworms can somehow jam the signals that would normally raise an army of inflammatory T cells. Instead, they encourage the immune system to make antibodies. There’s some evidence that suggests why tapeworms would go out of their way to do this. When the antibodies latch onto a cyst, the tapeworm drags them inside its shell and eats them. The tapeworm grows, in other words, by feeding on the futile efforts of the immune system.
Yet, like Toxoplasma, the tapeworm doesn’t want to kill its intermediate host. It’s only when the cyst begins to falter, when it can no longer hold out in the hope of getting into its final host, that it becomes dangerous. The tapeworm can no longer crank out the chemicals it uses to skew the immune system to antibodies. Now the immune system starts making inflammatory T cells tailored to the tapeworm, and they lead the macrophages and other immune cells into action. With such a huge target, the immune cells are worked up into a frenzy. They launch a violent attack that makes the tissue surrounding the cyst swell up, sometimes causing so much pressure that it can kill a person. It isn’t the parasite that kills the host, but the host itself.
An even more intimate knowledge of the human immune system can be found in the blood fluke, that passenger from Africa to Australia, that thirty-year-old Methuselah. When young flukes first penetrate the skin, they come to the attention of the immune system. Immune cells manage to kill some flukes early on, perhaps as the parasites struggle through the skin or as they pick their way through the lungs. But having cast off their freshwater coat, the flukes quickly put on a new one that the immune system never quite manages to figure out.
The reason their new coat is so confusing is that it’s partially made from the fluke’s host. You can see their disguise at work in a simple experiment. When parasitologists take a pair of the parasites out of a mouse and put them in a monkey, the flukes are unharmed and soon start churning out their eggs again. They aren’t so lucky if the scientists first inject antigens from mouse blood into the monkey. The injection acts like a vaccine, training the monkey’s immune system to recognize and destroy mouse blood antigens. If the flukes are transplanted from the mouse to the vaccinated monkey, the monkey’s immune system annihilates them. In other words, the flukes are so much like their mouse host that the monkey’s immune system treats them as if they were an organ transplanted from the mouse.
Even though the parasites in this experiment died, it demonstrated a brilliant disguise of theirs. Scientists aren’t sure how the flukes cloak themselves, but it seems that their coat is partially made out of the molecules studding our own blood cells. It may be that when the flukes pass by red blood cells or are attacked by white blood cells, they can tear out some of their host’s molecules and attach them to their own surface. Thus, to the eyes of the immune system, the parasites are nothing but red shadows in a red river.
These proteins aren’t the only things that blood flukes steal from our bodies. Complement molecules settle on the surface of our own cells just as they do on parasites. If they were allowed to go about their business of setting up beacons for macrophages, our immune systems would destroy our own bodies. To avoid this, our cells produce compounds such as decay accelerating factor (or DAF for short), which slices apart the complement molecules. Blood flukes can destroy the complement molecules that land on their own surfaces, and parasitologists have isolated the enzyme that they use. It turns out to be DAF.
It’s not clear whether the parasite steals it from its host’s cells or owns a gene for making the enyzme. It’s possible that at some point in the distant past, a virus that infected humans picked up the gene that makes DAF and then jumped to a blood fluke, adding the borrowed DNA to its new host. In either case, the molecule makes blood flukes as comfortable in our veins as the veins themselves.
In 1995, parasitologists studying blood flukes uncovered a paradox on the shores of Lake Victoria. They were studying Kenyan men who wash cars for a living along the lake. Working in the shallow water, they often get schistosomiasis, the disease caused by blood flukes. The prevalence of AIDS is high in the region as well, so that a fair number of the car-washers had both diseases. HIV destroys inflammatory T cells, the battle-hungry generals that lead macrophages against parasites. As these T cells die off, obscure parasites like Toxoplasma rampage through people with AIDS. Yet, blood flukes fare badly alongside HIV. In the Lake Victoria car-washers who had both AIDS and schistosomiasis, the blood flukes shed far fewer eggs than the ones in men who were sick with schistosomiasis alone.
The paradox of the car-washers stems from the fact that blood flukes need to use the human immune system to get their eggs out of their host. Without an immune system, they can’t reproduce. Once a female blood fluke lays her eggs in the vein walls, they begin secreting a cocktail of chemicals that manipulates the nearby macrophages. Under the spell of the eggs, the macrophages produce signaling molecules, the most important of which is called tumor necrosis factor alpha (or TNF-α). TNF-α is particularly good at causing inflammation by making the walls of the vein loosen up and by attracting more immune cells. The immune cells try to kill the egg with a spray of poisons, but the egg is protected by its tough shell. All the immune cells can do is wrap themselves around it, weaving an encapsulating shield of collagen.
The immune cells create this capsule (called a granuloma) in the hope of getting rid of the foreign object inside. If a splinter lodges in your thumb, for example, the cells will form a granuloma around it, which will then be carried up to the surface of the skin and be shed from your body. The same thing happens to a granuloma that forms around a fluke egg lodged in the wall of a vein. The granuloma moves through the vein wall and then through the wall of the intestines. This is exactly what the parasite needs to have happen, because it has to get out of its host’s body and hatch in water. The parasite, in other words, uses the white blood cells as porters to carry it across an impassable barrier. Once it’s on the other side, the immune cells in the granuloma are dissolved in the digestive juices of the intestines, but the tough-shelled egg survives and eventually tumbles out of the body. Hence the paradox of the car-washers of Lake Victoria: AIDS had robbed them of the immune cells the blood flukes needed to send off their young.