‘Is the real goal of immune cells to protect us or is it just profitable for us to think so?’

Mark Goloviznin on how a person’s immune system works and what viruses live in our body

‘Is the real goal of immune cells to protect us or is it just profitable for us to think so?’
Photo: shalamov.ru

“Can the immune cell act reasonably in the interests of the whole organism or other cells that will eat the rest of the “alien” and share with it? These aspects of the behaviour of immune cells need to be withdrawn from “the scientific unconscious” and modelling. At times we make up immune functions and study not what exists in fact but our own, probably delusive ideas of immunity,” thinks Candidate for Medical Sciences, Docent of Moscow State University of Medicine and Dentistry Mark Goloviznin. In an interview with Realnoe Vremya, he explained why the immune system looks like an anthill, what signs allow considering viruses living organisms and if immunity has single management.

“Just a handful of all microorganisms that live in a person turn out ‘wreckers’”

What viruses do live in the human body? Why don’t they harm it?

Firstly, indeed, viruses that inhabited it in the process of human life live in our organism, for instance, the well-known herpes virus or less known Epstein-Barr virus. In general a human is a super-organism that is inhabited not only by a virus but also a huge number of bacteria. The whole intestines are inhabited by bacteria that are mainly saprophytes and work for the good of the organism. Bacteria and viruses live in bronchopulmonary structures, on the skin, in the mucous membrane. In other words, there is some symbiosis of the human and bacteria, viruses also take part in it.

Secondly, during evolution many millions of years ago, genes of retroviruses built in the genome of the mammals (like modern AIDS virus) and began to produce a number of proteins of the immune system, that’s to say, the viruses became “anti-viruses” if we speak the computer language. This evolutionary biology really surprises, but this is true — we are a super-organism.

Do viruses penetrate the baby when it is in the mum’s uterus?

Not only a virus but also a number of big bacteria can penetrate inside the placenta. The treatment of tuberculosis in children is based on it. The famous BCG vaccine appeared because the infection of babies in the uterus or during the labour from ill mothers created a big problem. The babies died from severe forms of tuberculosis. The micro-bacterium of tuberculosis compared to the virus is a dinosaur against a mouse. This is why, of course, the virus goes through a series of biological barriers, it is normal.

Photo: yandex.ru
The famous BCG vaccine appeared because the infection of babies in the uterus or during the labour from ill mothers created a big problem

Why don’t viruses seriously harm the baby in the uterus?

There is a specialised system of immunity. It is mobile cells — lymphocytes and macrophages that interact with all “aliens” and somehow limit their activity. Just a handful of all microorganisms that live in a person turn out “wreckers”. There must appear some specific conditions when the immune system allows pathogens to develop.

The immune system is ambiguous if we simplify our story about it. There is inherent immunity that a new-born baby has and it has it regardless of the contact with the environment. And there is acquired immunity that develops when the organism contacts with the environment. Both of them work to make sure the organism will survive. Some immune cells refer to inherent immunity, the other part is to the acquired one.

By the way, does the inherent immunity in people from different continents differ?

Inherent immunity is also a complex system. The cells that belong to it have receptors recognising the so-called “images of pathogenicity” — it is recalcitrant proteins that are characteristic of a big number of kinds and types of different microorganisms. And inherent immunity reacts to them. In other words, it is a system of “carpet-bombing”, it isn’t strictly specific that acts against a specific virus or specific bacterium. Judging by existing research, many microorganisms have identical “images of pathogenicity” wherever they exist. While acquired immunity is a more specific system that has racial, regional and individual peculiarities.

“Without doubt a virus is a living organism”

Can a virus be considered as a living organism?

There is Engel’s definition that doesn’t satisfy everybody that life is a means of living of protein bodies. A virus is a protein body. Also, it has hereditary molecules — either DNA or RNA. In other words, it can proliferate, it reproduces its kind, sometimes in large quantities like we see now in the coronavirus case. It adapts to the environment, this is why without doubt a virus is a living organism. Though science knows living protein organisms that don’t contain molecules of nucleic acids, the so-called prions, agents of progressive nervous diseases of the human and animals. This is an issue at the intersection of immunology, medicine and philosophy.

Back to the virus: it has three very significant signs of living organisms — it has protein, reproduction of its kind with the help of nucleic acids and exchange of information with the environment.

Photo: lentachel.ru
Virus has three very significant signs of living organisms — it has protein, reproduction of its kind with the help of nucleic acids and exchange of information with the environment.

How is our organism constantly scanned for viruses?

Immunology as science has a very interesting dilemma. On the one hand, undoubtedly, our brain has a dominant, our individuality that asks the question “Me or not Me”. And as there is our mental and biological individuality, there must be factors that protect us. The second moment is that different viruses, saprophytes, pathogens objectively co-exist in our organism, and there are mobile “immune” cells — phagocytes, lymphocytes that interact with aliens, work in the organism. And the question is: “Is their real goal to protect us or is it just profitable for us to think so?”

I personally think that mobile immune cells are a kind of anthill. They live their own complicated life inside us, including during this life they perform a specific protective function, they can realise or not realise it. Another thing is that our ideas of their role may not comply with reality.

And as we are a super-organism, bacteria and viruses participate in the formation of our immune system. And if for some reasons the intestines or other organs of the person aren’t inhabited by bacteria at an early age, the immune system either doesn’t develop or develops poorly. There are such laboratory animals whose intestines are bereft of flora, and their immune system, especially acquired immunity, have signs of total underdevelopment.

In our super-organism immunity develops in contact with the environment from the intrauterine state and till the teenage. Inherent immunity activates, then acquired immunity catches up with it in development. And what is especially important is that suppressive mechanisms must develop in the immune system. The so-called cytokine storm is a feature of inherent immunity that can easily accelerate but is hard to stop. Acquired immunity is more mobile. It has targeted activation for a specific anti-gene and developed suppressive mechanisms braking the immune reaction when needed. Moreover, there is an organ of the immunity — thymus where those immune cells that can attack its own structures, not others, isolate and die. Cytokine storm can’t be stopped when there is developed inherent immunity, while acquired immunity, especially suppressive mechanisms, is poorly developed.

Photo: vesti.ua
The so-called cytokine storm is a feature of inherent immunity that can easily accelerate but is hard to stop

“An immune reaction can be compared with a car, if it speeded up and the brakes don’t work, it is unclear what is happening

What are cytokines?

It is small protein molecules that are generated by some immune cells, for instance, lymphocytes, macrophages, monocytes to signal and interact with other cells. There is even such a concept as a helper effect. For example, lymphocyte needs cytokines to produce anti-bodies, and this is done by another cell, that’s to say, there is a kind of dialogue. Thanks to cytokines, it was proved that the immune system was really a system, though it had been a theoretic concept for long. As early as Mechnikov stimulated the presence of the immune system but he couldn’t prove it in the early 20th century. When cytokines were discovered 30-40 years ago, it became clear how immune cells contacted each other. And this happens in any situation. This dialogue especially intensifies when there is inflammation, and there is a mass emission of cytokines.

This was known before the coronavirus too. For instance, during sepsis when bacteria end up in the blood and proliferate there intensively, immune cells respond by massively emitting cytokines. Such an occurrence was titled cytokine storm. And it turns out to be a double-edged sword because this storm not only helps but also hits the organism. A fever appears, arterial pressure goes down, generalised vascular penetration increases because cytokines influence not only immune cells but also vascular cells. Then blood clotting ability worsens, a lot of liquid goes to tissues, secondary infections take place there, and a person can die as a result of the cascade of these hyper-reactions.

Allergy is another example when the immune system “scores own goals”. Allergy patients have an increased, unreasonable reaction to the irritants (for instance, pollen) that most people don’t react to. This is also a hereditary defect of immune suppressive mechanisms.

And it is highly likely people who react to a virus infection with cytokine storm have some hereditary defects too, which haven’t been studied thoroughly. The current pandemic should stimulate the study of these factors.

This means that cytokine storm is a kind of disharmony between inherent immunity, which is type- or group-specific, which can easily be activated and is harder to stop, and acquired immunity, must restrict the immune reaction acting against specific agents and stop it on time. So an immune reaction can be compared with a car, if it speeded up and the brakes don’t work, it is unclear what is happening.

Photo: scientificrussia.ru
Cytokines are small protein molecules that are generated by some immune cells, for instance, lymphocytes, macrophages, monocytes to signal and interact with other cells

“It is still debatable if there is constant management of immunity from the single centre

Can the immune cell realise its actions?

As early as Mechnikov was asked such a question. Modern immunology appeared a bit more than a hundred years ago when phagocytosis was discovered. There is a poetic description of phagocytosis when Mechnikov pierced a tong into the body of a starfish and saw cells that gathered around the injury. But it wasn’t as simple then as it seems to us now. He was asked a question during the fight against religion: “Protection is the prerogative of supreme organisms. We can protect descendants, animals too. Do you mean that cells can think, act reasonably?” And Mechnikov managed to answer this question just indirectly. As an evolutionist biologist, he showed that phagocytosis wasn’t “God’s gift”, it appeared at certain stages of evolution of living organisms. Secondly, intercellular digestion came in handy: phagocyte is an absorbing cell. This helped Mechnikov to avoid the complex question of goal setting in immunology.

But a lot of categories of immunology still exist in the scientific unconscious. For instance, there is a concept of lymphocyte killer. Only immunologists were familiar with it until recently, now everybody can understand it is the lymphocyte that kills a microorganism that got in but doesn’t eat it. Why does it do this? Can the immune cell act setting goals in the interests of the whole organism or other cells that will eat the rest of the “alien” and share with it? These aspects of the behaviour of immune cells need to be withdrawn from the scientific unconscious and modelling. At times we make up immune functions and study not exists in fact but our own, probably delusive ideas of immunity.

Does the immune system have single management?

It is a question that scientists still debate. The immune system has its hierarchy, but it isn’t as strict as it is in the nervous system where there is a brain, spinal cord, peripheral nervous system. Everything is clear about the nervous system, and immunologists mainly took it into account when studying the immunity. As for the immune system, one thing is clear: there are mobile cells that migrate in the organism, as a result of the emission of cytokines they can gather in a place, while there are immune organs where these cells mature — marrow where lymphocytes making anti-bodies mature, and T lymphocytes mature that control cells of acquired immunity. Going through thymus is “training” so that the immune system will behave decently and won’t kill its cells and develop a hyperimmune reply because of which a person can die.

But it is still debatable if there is constant management of immunity from the single centre, which is the brain for the nervous system. At least the immune system is the most mobile regulatory system. It means its management is dictated by a specific situation.

By Matvey Antropov