What are cytokines for?
Protective mechanisms of organisms
Leonid Margolis, Post-Science
The body's immune system is a stunningly complex system consisting of many stages that have been formed throughout evolution. Cells, individual organisms and the whole population have protective mechanisms to fight viruses. A virologist told post-science about how bacteria, plants and animals are protected from viruses Leonid Margolis.
How does the virus enter the body?
Viruses are very small. For example, the particle size of a coronavirus or HIV is only about 150 nanometers. Due to the size of the virus, it is very easy to enter the body: we can inhale or swallow it, we can touch the surface on which it is located. At the same time, the virus does not have to get into the blood to provoke an infection. Different viruses choose different ways of infecting a person. For example, enteroviruses enter the stomach and cause upset of both the stomach and your plans.
Not every virus will be able to get inside the cell and infect us with something unpleasant. This is provided for evolutionarily: there are a lot of defective viral particles, with a broken sequence of RNA or DNA. Such viruses can penetrate through the cell membrane, but they will not reproduce inside the cell.
It is impossible to say how many virus particles are needed to infect a person for sure. This is a probabilistic process that is influenced by many factors at any given time. Of course, the more particles you are surrounded by, the higher the probability that some of them will be able to get inside and start an infection. But it is impossible to accurately calculate the chances of getting sick.
The work of the immune system
Protecting the body from a viral threat is a war with a constant arms race. Our immune system adapts to new conditions, but the basic principles remain unchanged. In the process of evolution, the human body has developed several stages of protection. They provide for an immune response at the level of a cell, an organism, or even the entire population.
The innate immunity that we have received in the process of evolution allows our body to neutralize a potentially dangerous or alien pathogen even before infecting cells. Such a system reacts to the appearance of a pathogen very quickly, but not accurately enough, since the reaction is provoked not by specific antigens (viruses), but by certain classes of antigens. Acquired immunity, also called adaptive, specific, works on the principle of creating an immunological memory in cells – remembering the reaction to the first contact with the pathogen and strengthening the reaction to each subsequent one. Thanks to this mechanism, for example, it is enough for people to get over chickenpox only once to get immunity to this disease.
Humans have inherited some defense mechanisms from plants and bacteria. Plants, for example, produce new RNA, which prevents the virus from multiplying further. This mechanism is called gene expression suppression (silencing). It binds to the viral genome in such a way that it prohibits replication, that is, reproduction of a new copy of this genome.
Bacteria are able to read a small piece of DNA of a bacteriophage that has entered a cell, and translates this piece into RNA with a gene-cutting mechanism. And it cuts out those genes that belong to the virus, leaving the healthy DNA of the cell.
Molecular memory, called CRISPR, is the bacterial equivalent of an acquired immune system capable of distinguishing beneficial viruses from harmful ones. This system makes changes to the bacterial genome and adds viral genes called spacers to it. Spacers form the memory of past interventional viruses. Special enzymes then recognize and destroy viruses as soon as they attempt to reinfect the bacteria.
The defense system of higher-level organisms is much more complicated. For example, cells can recognize a virus by foreign RNA and induce an intracellular response, namely the production of interferon, a protein responsible for blocking virus replication. It suppresses the reproduction of the virus inside the cell and "notifies" (exits the infected cell) neighboring cells of the body indicate that the enemy is a virus nearby. Thus, there is an inter-level transition from intracellular protection to the level of protection of the whole organism.
When a virus manages to infect a cell and start the replication mechanism of its copies, it can eliminate itself even before the moment when there are too many viral particles and they can force the cell to lyse – dissolve in order to release new viral particles outside. This process of cell self-destruction is called apoptosis.
Another antiviral barrier is special cells designed to recognize the virus entering the body and identify infected cells. Such cells react to virus proteins, which differ from healthy cell proteins in their chemical composition, and produce special agents – antibodies designed to destroy pathogens.
This system has its drawbacks: its calibration takes a lot of time, since the antibodies are specific and configured to recognize only one specific type of viral protein. Therefore, when the system is activated, it takes several days for it to multiply and adjust the production of antibodies. When the virus gets inside, the cell attacks its proteins, "cuts" it breaks them into pieces and exposes them on its surface. Then the antibodies can identify infected cells, because viral proteins remain on the surface of the cell membrane in combination with the histocompatibility complex MHC 1 – a special family of genes for recognizing "friend– foe".
However, viruses have also learned to bypass this system. There are, for example, viruses that suppress the mechanism of exposure of foreign proteins, and the cell cannot signal infection. Our immune system has an answer to this, too. Lymphocytes, which are called natural killers, react to the absence of the histocompatibility complex MHC 1 on the cell surface, which suppresses the virus. For lymphocytes, the absence of MHC 1 is already a sufficient reason to destroy such a cell.
Another helper in the fight against the invasion of viruses is temperature. The temperature increase through the pyrogen and hypothalamus is directly affected by interferon and cytokines interleukins 1 and 6. Many bacteria and viruses are temperature-dependent: under the influence of high temperature, they are destroyed or reduce their activity. Therefore, it is not necessary to bring down a non-life-threatening temperature: so you can interfere with the body's natural fight against the disease.
Interferon and cytokines
Interactions between immune cells that attack the virus are very complex. In order to neutralize the virus, some of them produce special molecules – cytokines (from Lat. cyto – "cell", kines – "movement"). Cytokines regulate the immune system of cells, their interaction with each other, are responsible for apoptosis, stimulation and suppression of their growth.
One of the classes of cytokines is the well-known interferon. In fact, there are many interferons, and their task is to regulate the interaction between immune cells. Interferons trigger processes in cells that lead to suppression of viral protein synthesis, assembly and release of viral particles. Interferons also activate genes that are important for protecting cells from viruses.
Currently, science is still far from understanding the mechanisms by which cytokines bind to each other. But it is already known, for example, that one cytokine can replace another: if you don't have any of the necessary cytokines, another one will take over its function.
Each cytokine is extremely important, but the mechanism of their action can be dangerous and lead to a disproportionately strong reaction of the immune system to the threat – a cytokine storm. When the body is unable to cope with the disease, the immune system begins to release cytokines uncontrollably and instead of helping to harm the body, destroying healthy cells along with the affected ones.
Suppression of immunity and excessive activation
The human body exists in a very delicate, special balance: it needs to alternate stimuli and suppression of stimuli. A constantly activated immune system is more dangerous for a person than useful. Many human diseases are associated with overly activated immunity – from diabetes to aging (although old age cannot be called a disease in the literal sense of the word).
As an example, the flu is familiar to everyone: if you get sick, your immune system has produced cytokines and activated T cells that defeated the virus. But after that, you need to stop them, turn them off, otherwise they can slow down the work of healthy cells.
According to this principle, autoimmune diseases are treated with the help of drugs that suppress immunity. Despite the fact that the mechanism of such diseases is well studied, the cause of their occurrence still remains the subject of scientific research and controversy. Autoimmune diseases, such as lupus or asthma, follow a single scenario: antibodies produced by the body's cells, for some reason, begin to attack the body's own tissues. A vivid example – HIV infection. Despite the fact that this is a disease of the immune system, the disease is supported by immune activation, because the virus multiplies only in activated cells.
Immunity of newborns
A significant part of our immune defense is formed in the womb through the placenta. However, if the immunity of a pregnant woman worked according to all the rules of the immune system, the embryo would not have the slightest chance to survive: the body would reject it as an alien cell. After all, pregnancy is a tissue transplant, in which there are foreign particles for the mother. In order to prevent rejection, there are special regulating T-cells that suppress the immunity of the uterus and allow the fetal egg to gain a foothold.
If we return to the question of whether immunity is transmitted from the mother through the placenta, then the answer is unequivocal: transmitted. Although the placenta filters the molecules, however, it passes the antibodies that have developed in the mother. This allows you to protect the newborn in the first days of life in an aggressive, unfamiliar environment. Quite a lot of antibodies are transmitted to the child with mother's milk, but only in the first few weeks. Then the child develops its own immunity for several months. This period is considered very dangerous in terms of infection with viruses, but thanks to vaccinations, the child's immunity receives additional support.
Of course, the genetic component of immunity is still present - for example, autoimmune diseases that are inherited, or resistance to HIV, which is observed in some people.
About the author: Leonid Margolis – Doctor of Biological Sciences, Head of the Department of Intercellular Interaction of the National Institutes of Health of the USA, Professor of the Faculty of Bioengineering and Bioinformatics of Lomonosov Moscow State University.
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