Your favorite food in life will be crabs, these gigantic, funny-looking spiders that crawl around the bottom of the ocean, have weird textures and are delicious. After months of mindful eating and dieting for a while, today is your night to indulge with friends. There is wine and a lot of crabs. But after the first bite of the crab, something strange happened. The body began to feel a little strange, a little uncomfortable.
You feel hot and start to sweat, and your ears, face, and hands feel a little weird. Suddenly you find it difficult to breathe, which makes you panic a little. After getting up, you have to sit down immediately because you feel dizzy. That’s when your friend asks if you’re okay. Then you wake up in an ambulance rushing to the hospital with a needle in your arm dripping chemicals into your body, quelling what nearly killed you.allergic reaction. You suddenly realize – you can no longer eat crabs.
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As we have seen many times in this book, the immune system is very tightly controlled. If it doesn’t react strongly enough, even a small infection can quickly turn into a fatal disease and kill you.
But if the reaction is violent, it can do more damage than any infection—the immune system can put your survival at greater risk than any pathogen. Think about Ebola, even this very sick horrible disease takes about six days to kill you. The immune system has the ability to kill you in about fifteen minutes. Anyone with allergies has experienced defenses against the dark side of the web.
It becomes deadly when the immune system loses its ability to calm itself. Thousands of people die every day from anaphylactic shock. Why does the immune system do this?
An allergy is an overreaction of the immune system to something that might not be so dangerous. This stands for mobilizing immune troops and getting ready to fight, even though no real threat exists. About one in five people in the West suffer from some form of allergy—the most common being immediate hypersensitivity, meaning symptoms are triggered quickly within minutes of exposure. It’s a bit like finding a bug in your living room and calling in the army to nuke the city you live in. This certainly solves the bug problem, but maybe it’s unnecessary to turn your house into a glowing pile of rubble. The most common immediate allergic reactions in developed countries are hay fever, asthma and food allergy, which vary in severity. Basically, you can have an allergic reaction to anything.
Some people are allergic to latex and can neither wear latex gloves nor a full-body latex suit (which is a real tragedy if that’s their preference). Others are allergic to the bites of certain insects, from bees to lice. There are also many kinds of food allergies, and of course you can be allergic to any kind of medication.
What makes the immune system make these responses are antigens, molecules of harmless substances. In the case of allergies, the antigens are called allergens, even though they are functionally the same—short stretches of protein, like those from crabmeat. As long as it is recognized by acquired immune cells and antibodies and can cause allergies, it is an allergen.
Why does the immune system think this is a good idea? Well, it doesn’t. It doesn’t think or do anything on purpose, but some mechanism is severely dysfunctional. In this case, the source of the allergic reaction is blood. This is where the most annoying part of the entire immune system, the IgE antibody, comes into play. You can thank IgE antibodies for much of the allergy-related suffering.
Specialized B cells that produce IgE are not resident in lymph nodes, but instead in the skin, lungs and gut. These are the places where IgE antibodies can do the most damage—they’re meant to deal with enemies breaking through the walls of defense, but now they’re directed at you. What do IgE antibodies actually do when you have an allergic reaction?
Anaphylaxis is produced in two steps
Allergies are always developed in two steps—first, a new mortal enemy needs to be encountered. Then, you must meet them again.
For example, you eat something like crab or peanuts, or you get stung by a bee. The first time it happened, everything was fine. The allergen is injected into your system, but for some reason, the B cells in the receptors that bind to the allergen are activated. They started making IgE antibodies against allergens like crabmeat protein, but now everything is quiet and nothing happens. Think of this step as having a bomb ready.
Now, after exposure to crab meat, a lot of IgE antibodies that are able to attach to the crab meat allergen are present in your system. But the IgE antibodies themselves don’t pose a problem because they aren’t particularly long-lived and dissolve after a few days. They need help from specialized cells in the skin, lungs, and gut — mast cells — that are especially receptive to IgE antibodies, to be a problem.
We briefly touched on mast cells earlier when we talked about inflammation. To refresh your memory, mast cells are big, bloated monsters that carry little bombs filled with extremely potent chemicals, like histamine, that cause rapid and widespread inflammation. Scientists are still debating the job of mast cells—some see it as important for early immune defense, others see it as a minor player. But what is certain is that mast cells can be superchargers for inflammation. Unfortunately, in the case of anaphylaxis, it is overzealous about its work.
Mast cells have receptors that bind and attach to the buttocks of IgE antibodies. So if you develop IgE after your first exposure to an allergen, the mast cells swoop toward the nail like a giant magnet.
So think of a “charged and armed” mast cell as a giant magnet covered with thousands of tiny spines. When allergens pass by, IgE antibodies on mast cells can easily bind to them. To make matters worse, IgE on mast cells can be stable for weeks or even months because binding to mast cells protects them from decay. So when you first come into contact with an allergen, these bombs are ready in your skin, lungs, or gut that can be activated very quickly. As time passed, nothing happened. Until you finally eat another load of crabmeat, flooding your system with allergens, allowing the IgE-coated mast cells to bind to them. Now armed with allergy bombs exploding inside.
Anaphylaxis looks like a chronic event
Armed mast cells degranulate, which is a nice way of saying they spit out all the chemicals. These chemicals are superchargers for inflammation, especially histamine. This can lead to all the extremely unpleasant things you experience during an allergic reaction. It tells the blood to constrict the blood vessels and allow fluid to flow into the tissues, causing redness, heat and swelling, itching and general discomfort.
If this happens in many parts of the body at once, it can lead to dangerous drops in blood pressure, which can be fatal. Histamine also stimulates mucus-producing and secreting cells to step up performance, causing extra and unnecessary snot and mucus production in the respiratory system.
But most dangerously, histamine can cause smooth muscle in the lungs to constrict, making breathing difficult or even impossible.
It’s not that you can’t take in air, it’s that air is trapped in your lungs, making it difficult to get the air out again. All the excess mucus that the mucous membranes make doesn’t help the situation at all. Because the lungs are full of mast cells, having an allergic reaction there can quickly become dangerous, as excess fluid and mucus fill the lungs, making it harder to breathe. The worst-case scenario could be anaphylactic shock, which can be fatal within minutes. Anaphylaxis is no joke.
We gave mast cells a bad name a few paragraphs ago, but that’s a little unfair. Because it doesn’t create all this chaos on its own. Mast cells have an equally harmful buddy. Once the mast cells are activated and degranulated, they also release cytokines, requiring another special cell, the basophil, to enhance the allergic response.
Basophils patrol the body in the blood until called upon. They also have receptors that bind IgE antibodies, which charge after initial exposure to antigen. Basophils are like the second wave of terror. Once mast cells trigger the first wave of an allergic response, they need to replenish their damaging histamine bombs, but are temporarily out of stock. Basophils fill the gap in the middle, ensuring that the allergic reaction doesn’t stop too quickly. They may also be proud of themselves, think they are doing something important, and innocently set their bodies on fire. Meanwhile, you’re scratching your skin or emptying an inflamed bowel. These two types of cells are responsible for the immediate allergic response.
Unfortunately, it’s not over yet. Many people with asthma know sadly that some allergic reactions are more of a chronic event than a one-off. Let’s meet the third (fortunately, the last) type of cell that sees an allergic reaction as a good idea!
Eosinophils ensure that the symptoms of an allergic reaction last for a while – only a few of them are present in the body, the majority are in the bone marrow, away from all the buzzing action. Cytokines released by mast cells and basophils activate them, but it takes a while for them to proliferate and colonize themselves before arriving at the party belatedly, where they unfortunately repeat their previous mistakes errors, causing inflammation and pain. You can rightly ask—why do your own immune cells do this?
The truth is, we don’t yet know why some people develop high levels of IgE antibodies when they come into contact with certain allergens or other substances. However, while not sure why some people are more severely affected than others, we think we know what IgE antibodies are there for in the first place:
They are the immune system’s superweapon, used against large parasites that are too large for phagocytes, macrophages and neutrophils to engulf. Especially the scariest of parasites, Parasitic worms, a menace humanity has had to contend with for millions of years. Let’s learn about the true purpose of IgE antibodies, at least partly to rehabilitate them.