About Indians and Chiefs: The Immune System

If you already want to go home, there are no objections. But I would recommend staying longer, it will be interesting. Do you want to know who does the cleaning in the lungs and maintains order? Who protects them and repairs them if necessary, and who destroys them? Who is a simple worker and soldier here, and who is the boss? Who doesn’t let in uninvited guests or shoo them out? At the same time, you will get acquainted with schemers living in the bronchi, ordinary and ritual murderers, cannibals, suicides. Come in boldly, here we have a whole menagerie!

A real drama is being played out in the lungs! The immune defense here is not organized in the same way as in other organs, but in a hurry. For nine long months, the lungs are splashed in a completely sterile maternal nutrient solution, and suddenly, for no reason at all, the first breath comes. Any other organ is given at least a little time to adapt to the “dirty” environment, or it is generally protected from it, like most internal organs. But it’s not like that with the lungs. From the first breath, from the first liter of air, hundreds of thousands of microbes enter the respiratory tract. This is a real invasion — millions of inanimate particles, dust, allergens, chemicals. And all you needed was a breath of oxygen! It’s like a party out of control. Who invited all these people here? What happens in the lungs in the first hours and days after birth can be compared to a trash can that someone emptied in the operating room: a stream of garbage literally falls on the lungs. Naturally, in such conditions, you will not want to cut the umbilical cord connecting you to the baby.

But there is no reason to panic. The lungs are coping. In most cases. And quite well. They have excellent organizational skills and seem to recruit assistants out of nowhere — quietly, quickly, and efficiently. An impressive achievement when you consider that the immune system of the lungs for nine months did nothing at all. No inflammation, no pathogens, nothing: sterile amniotic fluid runs through the respiratory tract, the immune system is in a state of complete relaxation. Just a fairy-tale idyll like working at the post office? Not really. The spirit of neoliberalism lives in your lungs. During pregnancy, they carried out such a rationalization of the immune system that they brought it almost to complete destruction. Some employees were sent on unpaid leave, the few remaining were transferred to a reduced working day. All that remains is to make coffee and deliver the mail once a week. Nothing else.

But shortly before the birth, the activity increases. In the bone marrow, there is a massive production of immune cells — white blood cells that enter the blood. Such a concentration of them in the blood, as now, will never be again. They circle around in the circulatory system, waiting for the signal. And now it’s time for the first breath! In an instant, the pores of the blood vessels open and an avalanche of white blood cells literally falls on the lungs. For the first two days after birth, their number in the lungs increases by 30 times! And they have something to do there. If the protective products contained in the mother’s milk are well protected from pathogens in the gastrointestinal tract of the newborn, then the lungs are absolutely defenseless. They need as many immune cells as possible, primarily in the areas of contact with the air, that is, on the bronchial mucosa and in the alveoli. The need for such cells is simply gigantic, so the recruitment of personnel is carried out without much discrimination. Immediately after birth, the immune system of the lungs consists of rather dark and uneducated individuals, only after some time they have leaders and there is a certain order. Stop shooting at anything that moves, because it may be a colleague. Protection begins to be carried out more carefully. Now, not every bacterium that timidly knocks on the door or just decides to pass by is subject to immediate destruction, often a polite warning is enough. But due to the lack of education, this team does not recognize any scammers at all, it still has a lot to learn. This process takes time. At the age of six, the immune system of the lungs is properly organized: tasks and positions are distributed, promotions are promised, hierarchy is observed, recruitment and training services, archives, all other departments are working like clockwork, at least this is the impression. Because in fact, this microcosm remains a grotesque and excitable company of indecisive personalities for the rest of its life. This is a microscopic version of the events taking place in the TV series Stromberg or more recently in the Oval Room of the White House. That’s why no one is surprised by the fact that events get out of hand from time to time and mistakes happen. And then the immune system, instead of solving problems, turns into a problem itself. The result is chronic inflammation and allergies. And, like any bad boss, the immune system is very reluctant to admit its mistakes, let alone correct them.

Who does what here? At first, the participants in your immune system receive the same basic education. All white blood cells mature in the bone marrow and, upon completion of primary school, have the right to enter the blood and go with it to the organs intended for them. In the blood, the grains are separated from the chaff: lymphocytes are sent for additional training, and simple workers — phagocytes — directly begin to serve in their organs. What happens to the selected lymphocytes? As the name suggests, their destination is the lymph nodes and the goiter gland. Its size is 6 centimeters, in humans it is located in the chest cavity. As puberty progresses, the goiter gland shrinks and disappears. This is a sign that the formation of the immune system is completely complete. In the lymph nodes and the goiter, the lymphocytes receive additional education necessary to perform more complex tasks. A group of B-lymphocytes will then be engaged in the production of so — called antibodies-specific proteins that neutralize pathogens. B-lymphocytes are highly skilled workers, but they never get to leadership positions and are subordinate to T-lymphocytes all their lives. These are like Harvard graduates who were trained in the goitre gland itself. There they not only learned to distinguish the cells of their own body from those of strangers, but also mastered some administrative functions.

At the head of the immune system of the lungs are the so-called T — helpers (from the English, help-to help). It turns out that these are helper cells? How so? And you thought… Don’t worry, it’s just a trick and a little coquetry. After all, at all management seminars, they say that “the main thing is the team” and so on. In fact, T-helpers have unlimited power. All decisions pass through their desk, and all information flows to them. They are the epitome of an overactive manager — a short-tempered choleric with a tendency to bipolarity. One moment he is soft and calm, the next he is suddenly on the verge of a heart attack. T-helper prefers not to get his hands dirty, he gives orders. It has employees to do the dirty work-phagocytes and cytotoxic T-lymphocytes.

In fact, the latter were also trained in an elite school, but then they realized that they did not have a soul for clerical work. Instead of building a career, they went underground and at their own risk patrol the lungs in the role of mysterious avengers: looking for cells infected with viruses, and degenerated cancer cells. At the same time, cytotoxic T-lymphocytes are guided by the principle “it is better to have one victim more than one less”, the possible consequences are not taken into account. However, despite all their independence, they also follow the instructions of T-helpers, although they are not always loyal enough to the management. They, like agents, can be “turned over”, and then they will destroy healthy cells of the body. The result is autoimmune diseases such as rheumatism or multiple sclerosis.

The supreme leadership also includes the headquarters of the advisors-regulatory T-lymphocytes. They should influence the most important decisions of T-helpers and prevent overly active defensive reactions. They are also responsible for deciding on the complete cessation of immune reactions and correcting erroneous decisions of T-helpers. But this rarely happens. More often than not, they evade responsibility and have only a limited influence on the T-helpers.

Complete the formation of the memory cell headquarters. By their nature, they are similar to accountants: they are always on their own mind and never contradict the instructions of their superiors. In the immune system, these cells play an important role, accumulating all the noteworthy information about the worst enemies and providing long-term immunity from pathogens of diseases such as measles, mumps, tetanus, diphtheria, scarlet fever. Microbes can deceive the immune system once, and the second time will not work: thanks to the memory cells, it will already be ready for their attack. Memory cells collaborate with antibody manufacturers, B lymphocytes, who receive precise instructions for making the right antibody for each infection. B-lymphocytes work quickly and efficiently. In the event of an infection, the production of antibodies increases dramatically and is adjusted to a specific pathogen. If we are talking about particularly dangerous infections, the protection does not stop even after recovery. Some B-lymphocytes continue to produce minimal amounts of the corresponding antibodies, and the body remains immune to this disease for many years. With a repeated attack of the same pathogen, the available antibodies quickly neutralize the aggressor, after which it will become an easy prey for phagocytes.

Phagocytes do not need higher education. After finishing elementary school, they risk their own lives and immediately start doing dirty work in their organs, including their lungs. Here, always, due to constant contact with the air, a large number of phagocytes is required. Among them, granulocytes and macrophages are distinguished, which can be translated as “big gluttons”.

Phagocytes are programmed to independently recognize the components of microbes and destroy them. However, they do not respond to training and fight only those pathogens that are programmed, without noticing all the others. For them, there are no semitones, their motto is “all or nothing”. They, like the Viking horde, in the course of their military campaigns against pathogens, sometimes cause serious damage to the lungs. In most cases, this side effect should be eliminated, but not always. Phagocytes have an extensive arsenal of enzymes and toxic proteins, with which they can destroy pathogens, however, like other cells. In general, these are quite primitive creatures that spend most of their time in gyms. But someone has to do the dirty work, too.

In the group of granulocytes in the lungs, two main representatives can be distinguished: neutrophils (named for their “neutral” color under the microscope) and eosinophils (having a red color and named after the goddess of dawn Eos). Neutrophils make up more than 95 percent of the total number of granulocytes and play an important role in protecting against pathogens, especially bacteria and fungi. But they can also be activated by tobacco smoke and other air pollutants and cause various diseases, in particular chronic bronchitis and COPD. The small group of eosinophils was originally designed to protect against parasites and worms. Thanks to the hygiene measures taken, they are practically left out of business in many parts of the world and now from idleness they arrange inflammatory foci in the bronchi, which leads to asthma.

The completion of the immune response is no less important than its initiation. It is particularly difficult to control phagocytes when the need for immune protection has disappeared. If this is not done, the recovery process will be difficult, and the inflammation in the worst case can go into a chronic form. That’s why T-helpers don’t stand on ceremony in choosing methods! In other words, they simply destroy phagocytes, though not with their own hands, but with the help of cytotoxic T-lymphocytes. Do you think it’s cruel? Everything is relative. Granulocytes also have an excessively rigid moral: if they are not needed within 24 hours, they voluntarily commit programmed suicide, after which the entire population of granulocytes is replaced with a new one. They say that you can’t enter the same river twice, and just as you can’t meet your granulocyte twice — they’re all new the next day.

Who did we miss? The first lady, the so-called dendritic cell, which serves as the chief strategist. In the immune system of the lungs, dendritic cells play a central role. They are in constant direct contact with the T-helpers and determine their daily agenda. These are the only cells that have the right to access the T-helper cells at any time and whisper solutions to them. Their function is to “present” foreign substances that enter the lungs: the dendritic cell decomposes this substance into workable parts and presents them to T-helpers. And they are already deciding what measures need to be taken. Friend or foe? Ignore, tolerate, or destroy? Should I put it in memory or not? The dendritic cell is able to influence such decisions. To do this, it deftly uses the communication networks of the immune system, and not only its official channels, but also unofficial ones (those “tweets” from cytokines — signaling substances with which immune cells communicate with each other at a distance). To the dendritic cell, all the gossip and rumors flock, and some of them it spreads itself. At best, the dendritic cell is a regulating and compensating element of the immune response, and at worst, it is a schemer who manipulates T-helpers, inciting them to make wrong decisions — with all the negative consequences that follow.

There is still the epithelium-a defensive wall! Epithelial cells form the surface of the airways and their outer protective layer. At the very beginning of the bronchi, this mechanical barrier consists of several layers, but towards the end – in the bronchioles and alveoli-it is barely noticeable. Any foreign substances-viruses, bacteria, fungi, harmful chemicals, allergens — first of all come across the epithelial layer. This is more than a passive barrier: epithelial cells can secrete protective substances into the bronchi, neutralize pathogens and bind harmful particles with mucus, preventing them from entering the deeper respiratory tract. After completing the primary measures, the epithelial cells, through signaling substances, call for help from other immune cells. However, “help” in this case is not quite the right word, in fact, for the epithelial cell, everything usually ends in death. To inform the cytotoxic T-lymphocyte of the attack of the virus is guaranteed to bring death on itself. Is it possible to say that the epithelial cell knows about this and consciously sacrifices itself? We don’t know. Fortunately, this melodrama always takes place in silence and unnoticed, because such a mass heroic death would hardly leave anyone indifferent. But it all depends on the approach. Even in a minor inflammation, if desired, you can see the plot for a Hollywood movie!

How exactly do the most important immune responses in the lungs work? Let’s take a look at the Oval Hall of the Immune System and listen to what is really happening on the upper floors of power.

Infection

Dendrita: Mr. President, I am reporting an invasion of the epithelium by a foreign dictator.

T-helper (President of the Immune System-PIS): What do you have there?

“What?” End it immediately. Send the Marines.

— In addition, we have received messages on Twitter in which he expresses doubts about your leadership abilities.

— Is he crazy?” I order an additional carpet bombing by the Air Force!

— On top of that, he made fun of your hair.”

“Over my hair?” Oh, who would say! Bring me my nuclear briefcase!

Regulatory T-lymphocyte: Mr. President, with all due respect, this is probably too much. We have evidence that the tweet about the hairstyle is fake. The situation is still quite uncertain, and we can’t yet give an unambiguous assessment of all the signals from the protective cells. Excessive defensive reaction can cause damage.

— I don’t care. “Fire and Fury”! Bomb the epithelial wall! Completely! The main thing is that this type does not survive.

“Completely?” The entire epithelium? And who will protect us from trespassers?

“It doesn’t matter. Then we’ll build a new wall, but this time a real one! And you know what? I’ll make the epithelial cells take all the expenses!

“Mr. President, calm down. Think about your blood pressure.

“All right. We will leave everything to the discretion of aviation.

Memory cell: Can we get a file, Mr. President?

• Absolutely. I want this soo … well, my son to learn a good lesson and not be annoyed in the future. Distribute flyers to all the posts so that they know him by sight.

Regulatory T-lymphocyte: Mr. President, the Air Force reports that the offensive has been repulsed.

• Great! You can withdraw your troops. And immediately after that, clean up the area.

At first glance, it seems to be an adequate and effective response, when all the persons involved responsibly perform their functions. That’s right. But if only it had always been like this. Unfortunately, it happens in a different way.

In the case of reduced immunity, events can unfold as follows:

IPR: What do you have there? I’m tired.

Dendrita: Mr. President, I am reporting an invasion by a foreign dictator.

“Hmmm.”

• Mr. President?
• Yes?

“A foreign dictator is extremely dangerous!”

“Hmmm.”

• Mr. President!

— Look at this, Dendrita. This guy just tweeted that he appreciates me as a great leader. And that I look good.

• Mr. President?

— And that I have a very large atomic button.” The biggest one. And this he admits to the whole public. I must say, this man is worthy of respect.

• Mr. President, the first news of the fighting and destruction is coming. We must act.
• This is fake news!
• Mr. President, we…

“Leave me alone. I have to go play golf. Is my plane ready?

Regulatory T-lymphocyte: Mr. President, we are defenseless.

“All right, send a granulocyte patrol over there. But only for the purpose of observation. Don’t interfere with anything.

“A patrol?” But that’s not enough.

“And with light weapons.” Let’s not scare a good person. Wow: “Great leader…” He’s a great guy.

Memory cell: Can we at least have a dossier, Mr. President? Just in case.

“No need. “Great leader …” We should invite him to play golf sometime.

• Mr. President!

“That’s it, I’ve already left!”

And with hay fever, the dialog may look like this:

PEASE: I’m bored. What do you have there?

Dendrita: Mr. President, Monsieur Senno has asked to see you.

— Who is this guy?” I don’t know him.

• Mr. President! This is Emanuel Senno, the French president.

“I’ve never heard of it.” Is he not dangerous?

“Definitely not. Maybe ignore it?

“I don’t know. What does he tweet?

• Hm.

“What?”

— You probably won’t be happy about that.”

— Why not?” Come on, speak up!

— In his last tweet, he posted a video with the hashtags #handshake and #weakling.

“Well, well. What else?

— He thinks his wife is better educated than yours.”

— What does he do?” Send the Marines.

• Mr. President?

“Send the Marines!” And aviation.

— But these are the French, our allies.

— I don’t care. I’ll teach this bastard a lesson.

Regulatory T-lymphocyte: Mr. President, with all due respect, this is probably too much. Monsieur Senno, according to our data, does not pose a threat to national security.

— I’m not interested. “Fire and Fury”! Immediately! And send in a squad of eosinophils, not neutrophils. This guy eats worms, doesn’t he?

Regulatory T-lymphocyte: Snails, actually. And in addition, we have no confirmation of these messages on Twitter.

PEASE: Don’t interrupt me. Dendrita, give him alternative facts!

Dendrita: Right away, Mr. President. You see, T-reg, he just tweeted: “I eat worms with Brigitte. Excellent.”

PIS: What an abomination! So, a special group of eosinophils. And I want Slizzy from the Secret Service called in. Immediately!

Memory cell: Yes. Can we get a file, Mr. President?

• Yes, and more! Bigger than my atomic button. Send the B-lymphocytes there. I want this guy drowned in antibodies next time!

Regulatory T-lymphocyte: Mr. President, with all due respect… B-lymphocytes do not produce antibodies against allies.

“Starting today, they’re producing it.” Otherwise, I’ll fire everyone!

“Of course, sir.

Communication is everything. In the lungs, health or disease depends on it. After all, immune cells are also human.