Causes of allergies

2024 Author: Malcolm Clapton | [email protected]. Last modified: 2023-12-17 03:44

What is an allergy - a disease or a protective reaction of the body, developed over the centuries? Scientists have different opinions, and, apparently, this is why a medicine that would once and for all relieve us of unpleasant symptoms has not yet been found. We bring you an article with interesting facts and research that sheds light on this problem.

I have never had a pronounced congenital allergy to something. Once at the age of six I was sprinkled due to the fact that I ate too much strawberries - that's all I can tell about my allergic reactions. Some of my friends have allergic reactions to the flowering of certain plants (poplar fluff) already in adulthood, and some of them stopped worrying about allergies after 13 years.

Why does this happen, how to protect yourself from it, is it possible to avoid it and what to do if it is hereditary?

Allergy (ancient Greek.

How allergies arise is still unclear

Scientists have not yet come to a common denominator and cannot say for sure where allergies come from, but the number of people suffering from one form or another of it is growing. Allergens include latex, gold, pollen (especially ragweed, amaranth and common cockle), penicillin, insect venom, peanuts, papaya, jellyfish stings, perfume, eggs, house tick feces, pecans, salmon, beef and nickel.

As soon as these substances start a chain reaction, your body sends out its response with a fairly wide range of reactions - from an annoying rash to death. A rash appears, the lips swell, chills may begin, stuffy nose and burns in the eyes. Food allergies can cause vomiting or diarrhea. In a very unlucky minority, allergies can result in a potentially fatal reaction known as anaphylactic shock.

There are medications, but none of them can permanently get rid of allergies. Antihistamines relieve symptoms, but they also cause drowsiness and other unpleasant side effects. There are drugs that really save lives, but they need to be taken for a very long time, and some types of allergies are treated only with complex methods, that is, one version of the drug is clearly not enough.

Scientists will be able to find a cure that will once and for all rid us of allergies, only if they understand the main causes of this disease. But so far they have decoded this process only partially.

Allergy is not a biological mistake, but our defense

It is this fundamental question that worries Ruslana Medzhitova, a scientist who has made several fundamental discoveries related to the immune system over the past 20 years and has won several important awards, including 4 million euros from the Else Kröner Fresenius Award.

At the moment, Medzhitov is studying a question that could revolutionize immunology: why do we suffer from allergies? So far, no one has an exact answer to this question.

There is a theory that allergy is a reaction to the venom of parasitic wormsliving in our body. In more developed and almost sterile countries, where this is rare, the unaccustomed immune system gives a sharper, more massive blow in response. That is, a child from some developing country who lives almost in a hut and calmly eats unwashed fruits may not even know what an allergy is, while children whose parents constantly wipe everything with sanitizers and twice a day they wash the floors of the apartment, have a whole bunch of “We can't do that! We are allergic to this!"

Medzhitov believes that this is wrong and that allergies are not just a biological mistake.

Allergy is a defense against harmful chemicals. Protection that helped our ancestors for tens of millions of years and still helps us today.

He admits that his theory is quite controversial, but he is confident that history will prove him right.

But sometimes our immune system hurts us

Ancient healers knew a lot about allergies. Three thousand years ago, Chinese doctors described an "allergic plant" that caused a runny nose in the fall.

There is also evidence that the Egyptian pharaoh Menes died from a wasp sting in 2641 BC.

What is food for one, poison for another.

Lucretius the Roman philosopher

And only a little over 100 years ago, scientists realized that such different symptoms could be the heads of one hydra.

Researchers have found that many diseases are caused by bacteria and pathogens, and our immune system fights these offenders - an army of cells that can release deadly chemicals and highly targeted antibodies.

It has also been found that, in addition to being protective, the immune system can be harmful.

At the beginning of the 20th century, French scientists Charles Richet (Charles Richet) and Paul Porter (Paul Portier) studied the effects of toxins on the body. They injected small doses of sea anemone venom into the dogs and then waited several weeks before introducing the next dose. As a result, the dogs received anaphylactic shock and died. Instead of protecting the animals, the immune system made them more susceptible to this poison.

Other researchers noticed that certain medications caused rashes and other symptoms. And this sensitivity developed on an increasing basis - a reaction inverse to the protection from infectious diseases that antibodies provide to the body.

Austrian physician Clemens von Pirke (Clemens von Pirquet) studied whether the body can change the body's response to incoming substances. To describe this work, he coined the word "allergy" by combining the Greek words alos (others) and ergon (work).

For the immune system, the allergic process is an understandable thing

In the decades that followed, scientists discovered that the molecular steps in these reactions were remarkably similar. The process was triggered when the allergen was on the surface of the body - skin, eyes, nasal passage, throat, respiratory tract, or intestines. These surfaces are filled with immune cells that act as border guards.

When the "border guard" encounters an allergen, it absorbs and destroys uninvited guests, and then supplements its surface with fragments of the substance. The cell then localizes some lymphatic tissue, and these fragments are passed on to other immune cells, which produce special antibodies known as immunoglobulin E or IgE.

These antibodies will trigger a response if they again stumble upon an allergen. The reaction will begin immediately after the antibodies activate the components of the immune system - mast cells, which trigger a flurry of chemicals.

Some of these substances can snag nerves, causing itching and coughing. Sometimes mucus starts to be produced, and contact with these substances in the respiratory tract can cause breathing problems.

This picture has been painted by scientists over the last century, but it only answers the question "How?", But does not explain at all why we suffer from allergies. And this is surprising, since the answer to this question is clear enough for most parts of the immune system.

Our ancestors faced the effects of pathogens, and natural selection left mutations that helped them repel these attacks. And these mutations are still accumulating so that we too can give a worthy rebuff.

Seeing how natural selection could create allergies was the hardest part. A strong allergic reaction to the most harmless things was hardly part of the survival system of our ancestors.

Allergies are also oddly selective.

Not all people are allergic, and only some substances are allergens. Sometimes people develop allergies at a fairly adult age, and sometimes children's allergies disappear without a trace (we say "outgrown").

The relationship between these parasites and allergies

For decades, no one really understood what IgE was for. He did not show any special abilities that could stop a virus or bacteria. Rather, it looks like we evolved to get one particular kind of antibody to get us in great trouble.

The first clue came to us in 1964.

Parasitologist Bridget Ogilvy (Bridget Ogilvie) investigated how the immune system responds to parasitic worms. She noticed that the body of rats infected with worms began to produce in large quantities what would later be called IgE. Subsequent studies showed that these antibodies signaled the immune system to attack and destroy the worms.

Parasitic worms pose a serious threat not only to rats, but also to humans.

For example, hookworms can draw blood from the intestines. Hepatic flukes can damage liver tissue and cause cancer, and tapeworms can cause cysts in the brain. More than 20% of people carry these parasites, and most of them live in low-income countries.

In the 1980s, a group of scientists vigorously advocated the link between these parasites and allergies. Perhaps our ancestors developed the body's ability to recognize proteins on the surface of worms and respond by producing IgE antibodies. The antibodies embedded by the cells of the immune system into the skin and intestines reacted quickly as soon as any of these parasites tried to enter the body.

The body has about an hour to bring the parasite's chances of survival to zero, he said. David Dunn (David Dunne), a parasitologist at the University of Cambridge.

According to the theory of parasites, the protein of parasitic worms is similar in shape to other molecules that our body encounters in our daily life. As a result, if we are confronted with harmless substances, the form of which is similar to the form of the protein of parasites, our body raises the alarm and the defense works idle. Allergy in this case is just an unpleasant side effect.

During his internship, Medzhitov studied the theory of worms, but after 10 years he began to have doubts. According to him, there was no point in this theory, so he started developing his own.

Basically, he thought about how our bodies perceive the world around us. We can recognize patterns of photons with our eyes and patterns of air vibration with our ears.

According to Medzhitov's theory, the immune system is another pattern recognition system that recognizes molecular signatures instead of light and sound.

Medzhitov found confirmation of his theory in the work Charles Janeway (Charles Janeway), an immunologist at Yale University (1989).

Advanced immune system and overreacting to invaders

At the same time, Janeway believed that antibodies have one big drawback: it takes several days for the immune system to develop its response to the aggressive actions of a new invader. He suggested that the immune system may have another line of defense that fires faster. Perhaps she can use the pattern recognition system to quickly detect bacteria and viruses and quickly begin fixing the problem.

After Medzhitov turned to Janeway, scientists began to work on the problem together. They soon discovered a new class of sensors on the surface of certain types of immune cells.

When confronted with invaders, the sensor grips the intruder and triggers a chemical alarm that helps other immune cells find and kill pathogens. It was a quick and accurate way to recognize and eliminate bacterial invaders.

So they discovered new receptors, now known as toll-like receptorswhich showed a new dimension in immune defense and which have been hailed as a fundamental principle of immunology. It also helped solve a medical problem.

Infections sometimes lead to catastrophic inflammation throughout the body - sepsis. In the United States alone, it strikes millions of people every year. Half of them die.

For years, scientists believed that bacterial toxins could cause the immune system to malfunction, but sepsis is just an exaggerated immune response against bacteria and other invaders. Instead of acting locally, it engages a line of defense throughout the body. Septic shock is the result of these defense mechanisms being activated much more strongly than the situation actually requires. The result is death.

Home alarm system for the body that gets rid of allergens

Despite the fact that initially Medzhitov was engaged in science not in order to treat people, his discoveries allow doctors to take a fresh look at the mechanisms that trigger sepsis, and thus find an appropriate treatment that will target the real cause of this disease - overreaction of toll-like receptors.

Medzhitov went further. Since the immune system has special receptors for bacteria and other offenders, perhaps it also has receptors for other enemies as well? That's when he started thinking about parasitic worms, IgE and allergies. And when he thought about it, something didn't work out.

Indeed, the immune system triggers the production of IgE when it encounters parasitic worms. But some research suggests that IgE is not really the main weapon against this problem.

Scientists have observed mice that cannot produce IgE, but the animals can still build up a defense against parasitic worms. Medzhitov was rather skeptical about the idea that the allergens were pretending to be parasite proteins. A large number of allergens, such as nickel or penicillin, have no possible analogs in the molecular biology of the parasite.

The more Medzhitov thought about allergens, the less important their structure seemed to him. Perhaps what connects them is not their structure, but their actions?

We know that very often allergens lead to physical damage. They rip off open cells, irritate membranes, rip proteins to shreds. Perhaps allergens are so damaging that we need to defend ourselves against them?

When you think of all the main symptoms of allergies - a stuffy red nose, tears, sneezing, coughing, itching, diarrhea and vomiting - they all have one common denominator. They are all like an explosion! Allergy is a strategy for ridding the body of allergens!

It turned out that this idea has long surfaced on the surface of various theories, but each time it is drowned again and again. Back in 1991, an evolutionary biologist Margie Profe (Margie Profet) argued that allergies fought toxins. But immunologists dismissed the idea, perhaps because Profe was an outsider.

Medzhitov, with his two students, Noah Palm and Rachel Rosenstein, published his theory in Nature in 2012. Then he began testing her. He first tested the link between injuries and allergies.

Medzhitov and his colleagues injected mice with PLA2, an allergen found in bee venom (which ruptures cell membranes). As Medzhitov predicted, the immune system did not react at all specifically to PLA2. It was only when PLA2 damaged the exposed cells that the body started producing IgE.

In another assumption, Medzhitov said that these antibodies would protect the mice, and not just make them sick. To test this, he and his colleagues gave a second injection of PLA2, but this time the dose was much higher.

And if the reaction to the first dose was practically absent in the animals, then after the second dose the body temperature rose sharply, up to death. But some mice, for reasons not entirely clear, developed a specific allergic reaction, and their bodies remembered and reduced the exposure to PLA2.

On the other side of the country, another scientist was doing an experiment that, as a result, further confirmed Medzhitov's theory.

Stephen Gally (Stephen Galli), chair of the pathology department at Stanford Medical University, spent years studying mast cells, mysterious immune cells that can kill people through an allergic reaction. He speculated that these mast cells might actually help the body. For example, in 2006, he and his colleagues discovered that mast cells destroy a toxin found in snake venom.

This discovery made Galli think about the same thing that Medzhitov thought about - that allergies could actually be a defense.

Galli and his colleagues performed the same experiments with mice and bee venom. And when they injected mice, which had never before encountered this type of poison, IgE antibodies, it turned out that their bodies received the same protection from a potentially lethal dose of poison, as the bodies of mice exposed to the action of this toxin.

Until now, despite all the experiments, many questions remain unanswered. How exactly does the damage caused by bee venom lead to a protective IgE response, and how did IgE protect the mice? These are exactly the questions that Medzhitov and his team are currently working on. In their opinion, the main problem is mast cells and their mechanism of work.

Jamie Cullen (Jaime Cullen) studied how IgE antibodies fix mast cells and make them sensitive or (in some cases) hypersensitive to allergens.

Medzhitov predicted that this experiment would show that allergen detection works like a home alarm system. In order to understand that a thief has entered your house, it is not at all necessary to see his face - a broken window will tell you about this. The damage caused by the allergen awakens the immune system, which picks up molecules in the immediate vicinity and produces antibodies to them. Now the intruder has been identified and it will be much easier to deal with him next time.

Allergies seem to be much more logical from an evolutionary point of view when viewed in the form of a home alarm system. Toxic chemicals, regardless of their source (poisonous animals or plants), have long been a threat to human health. Allergies were supposed to protect our ancestors by flushing these substances out of the body. And the discomfort that our ancestors felt as a result of all this, perhaps, forced them to move to safer places.

Allergy has more advantages than disadvantages

Like many adaptive mechanisms, allergies are not perfect. It reduces our chances of dying from toxins, but it still does not completely remove this risk. Sometimes, due to a too harsh reaction, an allergy can kill, as has already happened in experiments on dogs and mice. Still, the benefits of allergies outweigh the disadvantages.

This balance has shifted with the advent of new synthetic substances. They expose us to a wider range of compounds that can potentially damage and cause allergic reactions. Our ancestors could have avoided allergies simply by going to the other side of the forest, but we cannot get rid of certain substances so easily.

But Dunn is skeptical about Medzhitov's theory. He believes that he too underestimates the amount of proteins that they find on the surface of the parasitic worms. Proteins that could disguise themselves as a huge number of allergens from the modern world.

Over the next few years, Medzhitov hopes to convince skeptics with the results of other experiments. And this will possibly lead to a revolution in the way we treat allergies. And he will start with a pollen allergy. Medzhitov does not hope for a quick victory for his theory. For now, he is simply happy that he manages to change the attitude of people towards allergic reactions and they stop perceiving it as a disease.

You sneeze, which is good, because that way you protect yourself. Evolution doesn't care at all how you feel about it.