Why does the immune system attack its own cells? What destroys our immunity and how can it be strengthened? Measures to strengthen immunity

The immune system is the real defense of our body; it protects the human body from attacks by viruses, fungi, bacteria and other pathogenic organisms and substances. The immune system is capable of destroying body cells if they have degenerated into a malignant tumor. But sometimes the immune system cannot cope with a malignant tumor, for example, it may be a genetic reason, and the tumor begins to grow. A large tumor can affect the immune system in such a way that it stops responding to a malignant tumor. In this case, the tumor can affect the “protective” cells, and they begin to destroy the host body. If doctors can understand how tumors suppress the immune system, this will be a breakthrough in the treatment of cancer.

Immunity and tumor

For a long time, doctors believed that the immune system reacts poorly to cancer cells. Because the latter are very similar to normal cells. The immune system best resists malignant tumors that are of viral origin; the incidence of viral tumors increases in people with immunodeficiency. After some time, it became clear to doctors that not only the “similarity” of cells is the reason for the poor fight of the immune system against cancerous tumors.

It turned out that malignant tumors not only suppress the immune cells next to them, but also reprogram them, the immune cells begin to “serve” the cancer. The degeneration of an immune cell has several stages: at first it actively fights cancer, but then, dividing, it becomes part of the tumor. Scientists call this process “immunoediting.”

The first stage of immunoediting is the elimination process. External carcinogenic factors or mutations affect a normal cell, and it begins to “transform.” The cell gains the ability to divide unlimitedly, but it stops responding to regulatory signals that come from the body. The cell begins to synthesize “tumor antigens” on its surface and then sends “danger signals.”
Macrophages and T cells respond to these signals. The body’s “messengers” effectively destroy transformed cells, and tumor development is interrupted. But it happens that “precancerous” cells trigger an immune response. The transformed cell is weak and synthesizes fewer tumor antigens. Such cells are poorly recognized by the immune system; “traitor” cells survive the first immune response and then continue to divide.

The second stage of interaction between the body and the tumor begins. Which is called the “equilibrium stage”. The immune system can no longer completely destroy the tumor, but limits its growth. In this state, tumors “live” in the body for years; they are not detected during routine diagnostics.

Microtumors are not static; the properties of the cells they consist of gradually change as a result of the effects of mutations. Next comes selection; those cells that can most strongly resist the effects of the immune system remain to exist. Immunopresor cells appear. These cells passively avoid destruction and suppress the immune response. As a result, this evolutionary process leads to the fact that the body begins to die from cancer.

The third stage begins, which is called the “avoidance stage.” The tumor becomes practically insensitive to the effects of the immune system; the tumor begins to turn the activity of immune cells to its benefit. The tumor metastasizes and grows, there comes a time when doctors can diagnose the tumor. The previous stages proceed unnoticed; ideas about them are only an interpretation of several indirect data.

The significance of the dual behavior of the immune response in carcinogenesis

Today you can find many scientific articles that describe the fight of the immune system against malignant tumors. Almost the same amount of scientific material describes Negative influence the presence of immune cells in the tumor, which provoke its growth and the appearance of metastases. The concept of immunoediting explained the change in behavior of cells of the immune system.

Cells of the immune system are very plastic, so they can reorient themselves to the side of the tumor. The immune response, in our understanding, is the body’s fight, but in addition to the fight, the body must also spend energy on eliminating the damage that remains after the destruction of harmful cells. Cancer affects the body in such a way that white blood cells begin to perceive cancer cells as if they need help and begin to treat them.

Take for example macrophages, which are called “war cells” or “healing cells.” The tumor “deceives” macrophages in much the same way as leukocytes. Macrophages were discovered by Metchnikoff; these cells are capable of absorbing harmful substances. This phenomenon is called "phagocytosis", which became the basis of all immunology. Macrophages detect the “enemy” and rush towards it; in addition, they attract other cells with them that are responsible for protecting the body. After destroying the “intervenors,” macrophages help other cells clear the “battlefield”; they produce substances that promote rapid healing of damage. It is this ability of macrophages that cancer cells use for their own benefit.

There are two groups of macrophages, each group has its own predominant activity. M1 macrophages are “classically activated”, they are responsible for the destruction of foreign objects, including cancer cells. M1 macrophages can also attract other blood cells, such as killer T cells, to destruction. M2 macrophages are “healers”; they are responsible for tissue regeneration (recovery).

If the tumor contains big number M1-macrophages, then this makes it grow poorly, and as a result, complete remission may occur. M2 macrophages, on the contrary, secrete growth factors that promote the division of cancer cells. Experiments have shown that there are always many M2 cells around the tumor. Under the influence of M2 macrophages, M1 macrophages are reprogrammed and turn into the former. The “killers” can no longer cause damage or synthesize antitumor cytokines, but begin to release substances that promote tumor growth.

Proteins of the NF-kB family are the leading “programmers”; they control many genes that are so necessary for the activation of M1 macrophages. Important members of the family are p50 and p65, which form a p65/p50 heterodimer that influences gene activation in M1 macrophages. The p65/p50 heterodimer activates TNF in M1 macrophages, which responds to the acute inflammatory process, chemokines, interleukins, and cytokines. Excitation of these genes in M1 attracts to the focus a large number of immune cells. The NF-kB family homodimer or p50/p50 binds to promoters and blocks excitation. The degree of inflammation decreases. It is very important that there is a balance between heterodimer and homodimer in the body. Scientists have proven that the tumor disrupts the synthesis of p65 in M1 and promotes the accumulation of the p50/p50 complex.

Reactivation of the immune response

It turns out that there are cells around the tumor that destroy it, etc. who restore it. The future of cancer will depend on where the proportion shifts.

Experiments in modern medicine have shown that the process of “reprogramming” is reversible. Today, the most promising direction in onco-immunology is considered to be the development of an idea that can reactivate M1 macrophages.

Some types of tumors, such as melanoma, are perfectly treated with reactivation. The lactate molecule appears in tumors when there is a lack of oxygen due to rapid growth. Lactate enters the membrane channels of M1 macrophages. After this, the macrophage changes; oncological therapy will consist of blocking the M1 channels.

If scientists learn to control the immune response the way tumors control it, then the time will come when a person will be able to defeat cancer.

Scientists hope to find the causes of autoimmune diseases at the molecular genetic level.
Photo by Reuters

The immune system is designed to protect the body. But in some situations, its functioning is disrupted, and immune defense factors become aggressors in relation to the body’s own tissues. Treatment of such autoimmune diseases is very difficult: the main goal of therapy is the balance between reducing the activity of the immune system against its own body and preserving immunity.

One such disease is systemic lupus erythematosus. This is a severe systemic connective tissue disease that affects various internal organs. The disease has been known since ancient times, and received its name because of the characteristic rash on the bridge of the nose and cheeks, reminiscent of wolf bites. 90% of patients are women aged 20–40 years. In Russia, the number of patients with systemic lupus erythematosus increases annually and is already approaching 80 thousand, and in 40 thousand the disease steadily progresses and leads to early disability and death.

The cause of lupus is unknown. In developed countries, on average 3.5 years after diagnosis, 40% of patients are forced to stop working. Patients experience damage to the skin, joints, muscles, mucous membranes, heart, lungs, nervous system, more than half have kidney damage. Periods of exacerbation are followed by remission, but an active, constantly progressive course also occurs.

A conference held at the Research Institute of Rheumatology of the Russian Academy of Medical Sciences in Moscow was devoted to the problems of systemic lupus erythematosus.

The molecular genetic basis of the disease is poorly understood, so until recently there was no specific treatment. Academician of the Russian Academy of Medical Sciences Evgeniy Nasonov, director of the Research Institute of Rheumatology of the Russian Academy of Medical Sciences, emphasized that the entire arsenal of drugs used in rheumatology is used to treat systemic lupus erythematosus medicines, including non-steroidal anti-inflammatory drugs, hormones, anti-cell division agents, anti-malarial drugs and even extracorporeal blood purification methods. Most of them are used for systemic lupus erythematosus for off-label indications.

Understanding of the need to improve the pharmacotherapy of systemic lupus erythematosus has become an incentive to conduct large-scale clinical studies of various drugs. And first of all – genetically engineered biological drugs.

Immunological control of pathogenetic mechanisms became possible with the discovery of a molecular pathway that, by acting on it, can to some extent inhibit the development of systemic lupus erythematosus. This pathway involves a protein called B-lymphocyte stimulator (BLyS), from the tumor necrosis factor family. It has been found that suppressing BLyS can somewhat contain the runaway immune system.

The researchers, wanting to specifically block BLyS, relied on a human monoclonal antibody called belimumab. Against the background of its use, a decrease in the overall frequency of exacerbations and severe exacerbations of the disease was observed.

Academician Evgeniy Nasonov noted that in clinical trial Russian rheumatology centers in Moscow, St. Petersburg and Yaroslavl took part in the study of the monoclonal antibody belimumab. Its development is inextricably linked with progress basic research in the field of immunopathology of human diseases and is a striking example of the practical implementation of the concept of translational medicine. We can say that a new era is opening in the treatment of systemic lupus erythematosus, associated with the beginning of the widespread use of genetically engineered biological agents and the creation of a new class of drugs - BLyS inhibitors, which may have important therapeutic potential not only for systemic lupus erythematosus, but also for a wide range of human autoimmune diseases.

This system is a miracle of nature when it protects the body from foreign proteins, but it can also attack the very tissues it is designed to protect. The process of self-destruction is characteristic of all autoimmune diseases. It was as if the body had decided to commit suicide.

One of the fundamental mechanisms of such self-destructive effects is called molecular mimicry. Sometimes it happens that the enemy invaders that our cell soldiers are trying to destroy are very similar to ours own cells. The “casts” of the immune system that correspond to these foreign cells also correspond to our own. Then, under certain circumstances, the immune system destroys everything that resembles these “casts,” including the cells of its own body. This is an extremely complex process of self-destruction, involving many strategies developed by the immune system, all of which have one fatal flaw in common - the inability to distinguish foreign proteins from the body's own proteins.

What does all this have to do with our diet? Sometimes antigens that trick our body into attacking its own cells can be found in food. For example, during the digestion process, some proteins enter our bloodstream from intestinal tract without breaking down completely into amino acids. The remains of undigested proteins are perceived by our immune system as foreign bodies, and it creates “casts” for their destruction, triggering a self-destructive autoimmune process.

One of the food products that serves as a source of many foreign proteins that mimic proteins in our body is cow's milk. Most of the time, our immune system is quite smart. Just as the army has precautions to avoid shooting at its own people, the immune system has preventive mechanisms to prevent an attack on the body it is designed to protect. And although a foreign antigen looks exactly the same as one of the types of cells in the body’s own, the system is still able to distinguish its cells from foreign ones. She can use cells from her own body to train herself to create “imprints” against foreign antigens without destroying your own cells .

This can be compared to military exercises. When our immune system is functioning properly, we use our own body cells, which resemble antigens, to train without destroying them to prepare our soldiers to fight off foreign invaders. This is another example1 of nature’s exceptional ability to self-regulate.

The immune system uses a very delicate process to determine which proteins to attack and which to leave alone11. It is not yet clear how this incredibly complex process fails in autoimmune diseases. All we know is that the autoimmune system loses the ability to distinguish its own cells from foreign antigens and, instead of using its cells for training, destroys them along with the cells of the invaders.

Autoimmune diseases are diseases characterized by a malfunction of the immune system, due to which it begins to attack healthy tissues of the body. Symptoms of autoimmune diseases can vary greatly depending on the type of disease.

Even healthy tissue cells can have antigens.

Normally, the immune system reacts only to antigens of foreign or dangerous substances, but as a result of certain disorders, it can begin to produce antibodies to normal tissue cells - autoantibodies.

An autoimmune reaction can lead to inflammation and tissue damage. Sometimes, however, autoantibodies are produced in such small quantities that autoimmune diseases do not develop.

Expert opinion

Doctors still don't fully understand how the immune system works... and what happens when it starts working against us.

At least 80 autoimmune diseases are currently known, including lupus, multiple sclerosis, and diabetes. Type 1 and celiac disease - but there are at least 40 or more other diseases associated with malfunctions of the immune system.

The immune system has mechanisms that prevent an immune response to its own normal antigens. But there is always a possibility that these mechanisms can break down, and the older the individual, the higher the likelihood of some kind of failure. When this happens, autoantibodies are formed (antibodies that can interact with “self” antigens).

Unfortunately, doctors can help little - only eliminate symptoms and help patients identify risk factors and subsequently avoid potentially life-threatening situations.

What do we know

Pollution environment is also a risk factor for those who are genetically predisposed to autoimmune disease.

Second-hand smoke, chemicals in food or air, jet fuel fumes, exposure to UV rays and other forms of environmental pollution are triggers for the development of autoimmune diseases.

Vaccines, all vaccines, have an immunosuppressive effect, i.e. suppress immune function. Chemical substances contained in vaccines suppress the immune system; the virus they contain suppresses the immune system, and foreign DNA/RNA from animal tissue suppresses the immune system.

Wheat germ agglutinin (WGA) causes thymic atrophy in rats and can directly bind to and activate leukocytes. Anti-WGA antibodies in human serum cross-react with other proteins, indicating that they may contribute to the development of autoimmune diseases.

All body systems depend on enzymes. Changes in enzymes caused by fluoride can damage the immune system.

Deformed enzymes (with altered structure) are proteins, but they have now become foreign proteins (antigens) that we know cause autoimmune diseases, including lupus, arthritis, asthma and atherosclerosis.

Some nanoparticles have been linked to autoimmune diseases such as systemic lupus erythematosus, scleroderma and rheumatoid arthritis.

Some autoimmune diseases

Autoimmune reactions can be triggered in several ways:

• A substance that is normally present only in a certain part of the body enters the bloodstream. For example, a blow to the eye can cause intraocular fluid to enter the bloodstream; the immune system recognizes the intraocular fluid as foreign and attacks it.
• Substances normal to the body are changed, for example, by viruses, medicines, sunlight or radiation. The immune system may mistake these altered substances for foreign substances.
• Foreign substances that are very similar to natural substances in the body penetrate into the body. The immune system can mistakenly attack not only the first, but also the second. For example, the antigens of bacteria that cause strep throat are similar to heart tissue cells. In rare cases, strep throat may cause the immune system to attack a person's heart (a reaction similar to rheumatic fever).
• Cells that control antibody production - such as B lymphocytes (a type of white blood cell) - may not function properly and produce abnormal antibodies directed against healthy cells in the body.
• A predisposition to developing autoimmune diseases can be inherited. In people with this predisposition, any virus can cause this disorder. Hormonal factors can also influence the development of this type of disease - it is no coincidence that autoimmune disorders are most common in women.

Type 1 diabetes occurs when the pancreas is attacked by immune cells. Scientists at the École Polytechnique Fédérale de Lausanne (EPPL) have discovered what may trigger this attack, opening up new avenues for treatment.

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Type 1 diabetes is the rarest but most aggressive form diabetes mellitus, usually developing in children and adolescents. The patient's own immune cells begin to attack the pancreatic cells that secrete insulin, ultimately eliminating its production in the body. The immune system attacks certain proteins inside insulin-producing cells. However, it remains unclear how this actually happens. Scientists at FPSL have discovered that the attack on immune cells in type 1 diabetes may be caused by the release of proteins from the pancreas itself.

Self-destructive signals

Scientists from the Institute of Bioengineering, led by Steinunn Baekeskov, discovered that pancreatic beta cells actually secrete proteins that are attacked by the immune system. But it’s not just about proteins, it’s also about other components of the cell. It's about O exosomes, a substance that is small vesicles that are secreted by all types of cells to distribute molecules with different functions. But previous research has shown that exosomes can activate the immune system attack. Based on this, researchers from FPSL studied exosomes from human and animal pancreatic beta cells.

The results revealed that pancreatic beta cells from humans and rats secrete three proteins associated with type 1 diabetes and are actually used by clinicians to diagnose it in humans.

The researchers also discovered why the immune system attacks the pancreas first: when insulin-producing beta cells were stressed, they released large amounts of exosomes coated with proteins that activate immune processes. These proteins have potent inflammatory effects and may be involved in the induction of autoimmune responses in diabetes.

It is hoped that this will lead to new directions in the development of more effective methods treatment. Substances may be discovered performing the function of exosomes with molecules that inhibit the immune response. These synthetic molecules will inhibit the attack on pancreatic cells.