Self & Other
9. Allergies: When the Guards Panic
In 1902, a French physiologist named Charles Richet was on a yacht in the Mediterranean, owned by Prince Albert I of Monaco, who had a personal interest in marine biology and a habit of recruiting scientists to do research at sea.
Richet was studying the toxin of the Portuguese man-of-war — the long-tentacled, painfully stinging creature that drifts on the ocean’s surface. He wanted to understand the toxin well enough to develop a kind of immunity to it. The strategy seemed obvious. Vaccines worked by exposing animals to small, tolerable doses of a dangerous thing, prompting the immune system to make antibodies. Richet would do the same for jellyfish toxin. He injected dogs with very small doses of the venom, watched them recover, waited a few weeks for their immune systems to remember the encounter, and then injected them with a second small dose to see how much better they handled it.
The dogs died.
Not from the dose. The second dose was tiny — smaller, in some cases, than the first. The dogs that had handled the first injection without much trouble would, after the second injection, collapse within minutes. They would gasp for air. Their tongues would swell. Their hearts would race and then fail. They would be dead within the hour.
Richet was stunned. He had expected the second dose to provoke a milder response than the first, because that was how vaccines worked. Instead, he had produced the opposite. The animals’ immune systems, having “remembered” the toxin from the first encounter, were responding to the second encounter with a violence that the first encounter had never produced. The remembering had made them worse, not better.
He named the phenomenon anaphylaxis — from the Greek ana, against, and phylaxis, protection. Anti-protection. The opposite of immunity. He won the Nobel Prize for this in 1913, which is a strange thing to win a Nobel Prize for, because what he had discovered was, essentially, that the immune system can kill you.
Anaphylaxis is the extreme end of a spectrum. The same kind of immune response — milder, more localized — is what happens when someone with hay fever encounters pollen, when someone with a cat allergy encounters a cat, when someone with a peanut allergy gets a trace of peanut into their food. The mechanism is the same. The severity varies enormously. At one end, a slightly itchy nose. At the other end, Richet’s dogs.
This is the chapter where we ask the question that’s been hanging in the air since Richet: what on earth is this for?
IgE
Most of the antibodies we’ve talked about in this book belong to a class called IgG — the standard antibody, the one your body makes most of, the one that does most of the work of recognizing and tagging foreign things. When your body decides to mount an antibody response against a virus, it mostly makes IgG. When you get vaccinated, the antibodies that protect you are mostly IgG.
Allergies are not driven by IgG. Allergies are driven by a different antibody class, much smaller in normal circumstances, called IgE. The E stands for nothing in particular — it was the fifth class to be discovered, and the letters just continued in alphabetical order.
IgE behaves differently from IgG in two important ways.
First, almost all of the IgE in your body is not floating in your bloodstream. It is stuck to the surface of certain immune cells. Specifically, it is stuck to mast cells, which sit just under the surfaces of your skin and the linings of your nose, throat, lungs, and gut, and to basophils, which are similar cells circulating in the blood. Each mast cell has, on its surface, tens of thousands of IgE molecules, all reaching out into the surrounding tissue, all waiting for something to bind to them.
Second, when an IgE molecule does bind to its target, the response is almost instantaneous. The mast cell does not engage in slow, careful immunology. It is a cell loaded, like a spring trap, with granules full of pre-made chemicals. The most famous of these chemicals is histamine. There are dozens of others. When IgE on the cell’s surface binds to its target, the cell, within seconds, dumps the entire contents of those granules into the surrounding tissue.
Histamine, released into a tissue, does several things very quickly. It makes blood vessels widen and leak. It makes smooth muscle (the kind in your airways and gut) contract. It makes nerve endings fire, producing itching. It recruits more immune cells. And it does all of this within seconds, not hours. This is why an allergic reaction feels so different from a normal infection. A virus takes days to make you sick. An allergen, in the right person, can make you sick in less than a minute.
The runny nose, the itchy eyes, the swelling, the wheezing, the hives — these are all symptoms of mast cells dumping their contents into local tissue. The mechanism is the same regardless of trigger. The pollen-allergic person has IgE on their mast cells that recognizes a particular pollen protein. The peanut-allergic person has IgE on their mast cells that recognizes a particular peanut protein. The substance differs. The cellular machinery is identical.
In anaphylaxis, the same thing happens, but everywhere at once. Mast cells throughout the body dump their granules simultaneously. Blood vessels everywhere widen and leak; the airways narrow; blood pressure crashes. The body, attempting to respond to a tiny exposure, briefly mounts a response so violent that it cannot survive its own defense.