The term "immunity" originated from the Latin word "immunitas" - liberation, getting rid of something. He entered medical practice in the 19th century, when they began to denote "liberation from illness" (French dictionary Litte, 1869). But even long before the term appeared among physicians, there was a concept of immunity in the meaning of a person's immunity to disease, which was designated as "the self-healing force of the body" (Hippocrates), "vital force" (Galen) or "healing force" (Paracelsus). Doctors have long known the inherent immunity (resistance) in humans from birth to animal diseases (for example, chicken cholera, dog plague). Now it is called innate (natural) immunity. Since ancient times, doctors have known that a person does not get certain diseases twice. So, back in the 4th century BC. Thucydides, describing the plague in Athens, noted the facts when people who miraculously survived could take care of the sick without the risk of getting sick again. Life experience has shown that people can develop a persistent resistance to reinfection after suffering severe infections, such as typhus, smallpox, scarlet fever. This phenomenon is called acquired immunity.

In the late 18th century, Englishman Edward Jenner used cowpox to protect humans from smallpox. Convinced that artificial human infection is a harmless way to prevent serious illness, he conducted the first successful experiment on humans in 1796.

In China and India, smallpox vaccination was practiced for several centuries before its introduction in Europe. The sores of a person who had had smallpox scratched the skin of a healthy person, who usually then transferred the infection in a weak, not fatal form, after which he recovered and remained resistant to subsequent infections with smallpox.

100 years later, the fact discovered by E. Jenner formed the basis of L. Pasteur's experiments on chicken cholera, which culminated in the formulation of the principle of prevention of infectious diseases - the principle of immunization with weakened or killed pathogens (1881).

In 1890, Emil von Bering reported that after the introduction of not whole diphtheria bacteria into the body of an animal, but just a certain toxin isolated from them, something appears in the blood that can neutralize or destroy the toxin and prevent the disease caused by the whole bacterium. Moreover, it turned out that preparations (serums) prepared from the blood of such animals healed children who were already sick with diphtheria. The substance that neutralized the toxin and appeared in the blood only in its presence was called antitoxin. Subsequently, substances similar to him began to be called a general term - antibodies. And the agent that causes the formation of these antibodies began to be called the antigen. For these works, Emil von Behring was awarded the 1901 Nobel Prize in Physiology or Medicine.

Later P. Ehrlich developed on this basis the theory of humoral immunity, i.e. immunity provided by antibodies, which, moving through the liquid internal media of the body, such as blood and lymph (from Latin humor - liquid), infect foreign bodies at any distance from the lymphocyte that produces them.

Arne Tiselius (1948 Nobel Prize in Chemistry) showed that antibodies are just ordinary proteins, but with a very high molecular weight. The chemical structure of antibodies was deciphered by Gerald Maurice Edelman (USA) and Rodney Robert Porter (UK), for which they received the Nobel Prize in 1972. It was found that each antibody consists of four proteins - 2 light and 2 heavy chains. Such a structure in an electron microscope looks like a "slingshot" (Fig. 2). The part of an antibody molecule that binds to an antigen is very variable, which is why it is called variable. This region is located at the very tip of the antibody, so the protective molecule is sometimes compared to tweezers, using sharp ends to grasp the smallest details of the most intricate clockwork. The active center recognizes small areas in the antigen molecule, usually consisting of 4-8 amino acids. These regions of antigen fit into the antibody structure "like a key to a lock." If antibodies cannot cope with the antigen (microbe) on their own, other components and, first of all, special "eater cells" will come to their aid.

Later, the Japanese Susumo Tonegawa, based on the achievement of Edelman and Porter, showed what no one, in principle, could even expect: those genes in the genome that are responsible for the synthesis of antibodies, unlike all other human genes, have an amazing ability to repeatedly change their structure in individual cells of a person during his life. At the same time, varying in their structure, they are redistributed in such a way that they are potentially ready to ensure the production of several hundred million different antibody proteins, i.e. much more than the theoretical amount potentially acting on the human body from the outside of foreign substances - antigens. In 1987, S. Tonegawa was awarded the Nobel Prize in Physiology or Medicine "for the discovery of the genetic principles of antibody generation."

Simultaneously with the creator of the theory of humoral immunity, Ehrlich, our compatriot I.I. Mechnikov developed the theory of phagocytosis and substantiated the phagocytic theory of immunity. He proved that animals and humans have special cells - phagocytes - capable of absorbing and destroying pathogenic microorganisms and other genetically foreign material that appears in our body. Phagocytosis has been known to scientists since 1862 from the works of E. Haeckel, but only Mechnikov was the first to connect phagocytosis with the protective function of the immune system. In the subsequent long-term discussion between the supporters of the phagocytic and humoral theories, many mechanisms of immunity were revealed. Phagocytosis, discovered by Mechnikov, was later called cellular immunity, and antibody formation, discovered by Ehrlich, was called humoral immunity. It all ended with the fact that both scientists were recognized by the world scientific community and shared the Nobel Prize in Physiology or Medicine for 1908.

Immunology is the science of the body's defense reactions aimed at preserving its structural and functional integrity and biological individuality. It is closely related to microbiology.

At all times there were people who were not affected by the most terrible diseases that claimed hundreds and thousands of lives. In addition, even in the Middle Ages, it was noticed that a person who suffered an infectious disease becomes immune to it: that is why people who recovered from plague and cholera were attracted to caring for the sick and to the burial of the dead. Physicians became interested in the mechanism of resistance of the human body to various infections for a very long time, but immunology as a science arose only in the 19th century.

Vaccine development

The pioneer in this area can be considered the Englishman Edward Jenner (1749-1823), who managed to save humanity from smallpox. Observing cows, he drew attention to the fact that animals are susceptible to infection, the symptoms of which are similar to smallpox (later this disease in cattle was called "cowpox"), and on their udders, bubbles are formed that strongly resemble smallpox. During milking, the fluid contained in these vesicles was often rubbed into people's skin, but milkmaids rarely had smallpox. Jenner could not provide a scientific explanation for this fact, since then it was not yet known about the existence of pathogenic microbes. As it turned out later, the smallest microscopic creatures - viruses that cause cowpox, are somewhat different from those viruses that infect humans. However, the human immune system reacts to them as well.

In 1796, Jenner inoculated a liquid taken from the pock marks of cows into a healthy eight-year-old boy. The latter developed a slight discomfort, which soon passed. A month and a half later, the doctor inoculated him with smallpox. But the boy did not get sick, because after the vaccination, antibodies developed in his body, which protected him from the disease.

The next step in the development of immunology was made by the famous French physician Louis Pasteur (1822-1895). Based on Jenner's work, he expressed the idea that if you infect a person with weakened microbes that cause a mild illness, then in the future the person will not get sick with this ailment. His immunity works, and his leukocytes and antibodies will easily cope with pathogens. Thus, the role of microorganisms in infectious diseases has been proven.

Pasteur developed a scientific theory that allowed vaccination against many diseases, and, in particular, created a vaccine against rabies. This extremely dangerous disease for humans is caused by a virus that infects dogs, wolves, foxes and many other animals. In this case, the cells of the nervous system are affected. The sick person develops hydrophobia - it is impossible to drink, because the water causes cramps in the pharynx and larynx. Death can result from paralysis of the respiratory muscles or cessation of cardiac activity. Therefore, if a dog or other animal bites, it is necessary to urgently carry out a course of vaccinations against rabies. The serum, created by a French scientist in 1885, is successfully used to this day.

The immunity against rabies only lasts for 1 year, so in case of repeated bites after this period, vaccinations should be done again.

Cellular and humoral immunity

In 1887, the Russian scientist Ilya Ilyich Mechnikov (1845-1916), who worked for a long time in Pasteur's laboratory, discovered the phenomenon of phagocytosis and developed the cellular theory of immunity. It consists in the fact that foreign bodies are destroyed by special cells - phagocytes.

In 1890, the German bacteriologist Emil von Bering (1854-1917) established that in response to the introduction of microbes and their poisons, the body produces protective substances - antibodies. Based on this discovery, the German scientist Paul Ehrlich (1854-1915) created the humoral theory of immunity: foreign bodies are eliminated by antibodies - chemicals delivered by the blood. If phagocytes can destroy any antigens, then antibodies are only those against which they were developed. Currently, the reactions of antibodies with antigens are used in the diagnosis of various diseases, including allergic ones. In 1908, Ehrlich, together with Mechnikov, was awarded the Nobel Prize in Physiology or Medicine "for his work on the theory of immunity."

Further development of immunology

At the end of the 19th century, it was found that when transfusing blood, it is important to take into account its group, since normal foreign cells (erythrocytes) are also antigens for the body. The problem of the individuality of antigens became especially acute with the emergence and development of transplantation. In 1945, the English scientist Peter Medawar (1915-1987) proved that the main mechanism of rejection of transplanted organs is the immune: the immune system perceives them as foreign and throws antibodies and lymphocytes to fight them. And only in 1953, when a phenomenon opposite to immunity was discovered - immunological tolerance (loss or weakening of the body's ability to respond to a given antigen), transplant operations became much more successful.

Immunity is the body's defense system against external influences. The term itself comes from the Latin word translated as "liberation" or "getting rid of something." Hippocrates called it "the self-healing power of the body", and Paracelsus called it "healing energy." First of all, you need to understand the terms associated with the main defenders of our body.

Natural and acquired immunity

Even in ancient times, doctors knew the immunity of humans to animal diseases. For example, plague in dogs or chicken cholera. This is called innate immunity. It is given to a person from birth and does not disappear throughout life.

The second appears in a person only after he suffers an illness. For example, typhus and scarlet fever are the first infections to which doctors have discovered resistance. During the process of illness, the body creates antibodies that protect it from certain microbes and viruses.

The enormous importance of immunity is that after a cure, the body is ready to face re-infection. This is facilitated by:

• preservation of the antibody model for life;
• recognition by the body of a "familiar" disease and rapid organization of defense.

There is a milder way to acquire immunity - this is vaccination. There is no need to fully experience the disease. It is enough to introduce a weakened disease into the bloodstream to "teach" the body to fight it. If you want to know what the discovery of immunity gave humanity, you should first find out the chronology of the discoveries.

A bit of history

The first vaccination was given in 1796. Edward Gener was convinced that artificial infection with smallpox from the blood of a cow was the best option for acquiring immunity. And in India and China, people were infected with smallpox long before they began to do it in Europe.

Preparations made from the blood of such animals came to be called serums. They became the first remedy for disease, which gave humanity the discovery of immunity.

Serum as a last chance

If a person is sick and cannot cope with the disease on their own, he is injected with serum. It contains ready-made antibodies that the patient's body, for whatever reason, cannot develop on its own.

These are extreme measures, they are only necessary if the patient's life is in danger. Serum antibodies are obtained from the blood of animals that are already immune to the disease. They receive it after vaccination.

The most important thing that was given to mankind by the discovery of immunity is an understanding of the work of the body as a whole. Scientists have finally figured out how antibodies appear and what they are for.

Antibodies - fighters against dangerous toxins

Antitoxin began to be called a substance that neutralizes the waste products of bacteria. It appeared in the blood only in case of ingestion of these dangerous compounds. Then all such substances began to be called a general term - "antibodies".

Laureate Arne Tiselius experimentally proved that antibodies are ordinary proteins, only having a large A, two other scientists - Edelman and Porter - deciphered the structure of several of them. It turned out that the antibody consists of four proteins: two heavy and two light. The molecule itself is shaped like a slingshot.

And later, Susumo Tonegawa showed the amazing ability of our genome. The DNA regions that are responsible for the synthesis of antibodies can change in every cell of the body. And they are always at the ready, in any danger they can change so that the cell begins to produce protective proteins. That is, the body is always ready to produce many different antibodies. This diversity more than exceeds the number of possible alien influences.

The value of the discovery of immunity

The very discovery of immunity and all the theories put forward about its action allowed scientists and doctors to better understand the structure of our body, the mechanisms of its reactions to viruses, and This helped to defeat such a terrible disease as smallpox. And then vaccines were found for tetanus, measles, tuberculosis, whooping cough, and many others.

All these advances in medicine have made it possible to greatly increase the average person and improve the quality of medical care.

In order to better understand what the discovery of immunity gave humanity, it is enough to read about life in the Middle Ages, when there were no vaccinations and serums. Look at how dramatically medicine has changed, and how much better and safer life has become!

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Every person is familiar with the mysterious word "immunity" - the body's defense mechanism against harmful and foreign objects. But how does the immune system work, is it coping, and how can we help it? How did the discoveries take place in this area and what did they give and give?

Ilya Mechnikov and his discovery

Even in ancient times, people understood that the body has special protection. During epidemics of smallpox, plague and cholera, when the funeral teams did not have time to remove corpses from the streets, there were those who coped with the disease or those whom it did not touch at all. This means that there is a mechanism in the human body that protects it from external infections. It was called immunity (from the Latin immunitas - liberation, getting rid of something) - this is the body's ability to resist, neutralize and destroy foreign cells, various infections and viruses.

Even in ancient China, healers noticed that a person who had once been ill no longer fell ill with smallpox (a smallpox epidemic first swept across China in the 4th century). These observations led to the first attempts to protect against infection by artificial infection with infectious material. Physicians began to blow crushed smallpox scabs into the noses of healthy people, and made "injections" to healthy people from the contents of the vesicles of smallpox patients. In Turkey, the first "guinea pigs" were girls who were raised for a harem so that their beauty would not suffer from smallpox scars.

Scientists have long struggled to explain these phenomena.

The founding father of immunology at the end of the 19th century is the famous French physician Louis Pasteur, who believed that the body's immunity to microbes and diseases is determined by the fact that the human body is not suitable for microbes as a breeding ground, but he could not describe the mechanism of the immune process.

For the first time this was done by the great Russian biologist and pathologist Ilya Mechnikov, who from childhood showed an interest in natural science. After graduating from the 4-year course of the natural department of Kharkov University in 2 years, he was engaged in research in the embryology of invertebrates and at the age of 19 he became a candidate of sciences, and at 22 he became a doctor of sciences and headed the newly organized Bacteriological Institute in Odessa, where he studied the action of the protective cells of a dog , rabbit and monkey on microbes that cause various infectious diseases.

Later, Ilya Mechnikov, studying the intracellular digestion of invertebrates, observed under a microscope the larva of a starfish and a new idea dawned on him. Just as in humans, inflammation occurs with a splinter, when the cells oppose a foreign body, he suggested that something similar should happen with a splinter inserted into any body. He inserted a rose thorn into the mobile transparent cells of a starfish (amoebocytes) and after a while saw that amoebocytes had accumulated around the splinter and tried to either absorb the foreign body, or created a protective layer around it.

So Mechnikov got the idea that there are cells that perform a protective function in the body.

In 1883, Mechnikov spoke at the congress of naturalists and doctors in Odessa with a report "The healing powers of the body", where he first voiced his idea of ​​the special organs of the body's defense. In his report, he first suggested that the spleen, lymph glands and bone marrow should be included in the system of healing organs of vertebrates.

This was said more than 130 years ago, when doctors seriously believed that the body was freed from bacteria only with the help of urine, sweat, bile and intestinal contents.

In 1987, Mechnikov and his family left Russia and, at the invitation of the microbiologist Louis Pasteur, began to head a laboratory at the private Pasteur Institute in Paris (Louis Pasteur is known for having developed vaccinations against rabies, using the dried brain of rabies infected with rabies, against anthrax, cholera chickens, rubella pigs).

Mechnikov and Pasteur introduced a new concept of "immunity", by which they understood the body's immunity to various kinds of infections, any genetically foreign cells.

Mechnikov called the cells that either absorbed or enveloped a foreign body that entered the body phagocytes, which in Latin means "eaters", and the phenomenon itself - phagocytosis. It took the scientist more than 20 years to prove his theory.

Phagocytic cells include leukocytes, which Mechnikov divided into microphages and macrophages. "Radars" of phagocytes detect a harmful object in the body, destroy it (destroy, digest) and expose the antigens of the digested particle to the surface of their cell membrane. After that, coming into contact with other cells of the immune system, the phagocyte transmits them information about the harmful object - bacteria, viruses, fungi and other pathogens. These cells "memorize" the presented antigen, so that when it hits it again, they can fight back. That was his theory.

Speaking about Ilya Mechnikov, I will add that he created the first Russian school of microbiologists, immunologists and pathologists, was multifaceted in his knowledge (for example, he was interested in aging issues) and died in a foreign land in 1916 after suffering heart attacks at the age of 71. Mechnikov had to endure the death of his first wife from tuberculosis, a violent scientific confrontation with German microbiologists Paul Ehrlich and Robert Koch, who completely rejected the theory of phagocytosis. Then Mechnikov came to the Hygienic Institute in Berlin led by Koch to show some of the results of the work on phagocytosis, but this did not convince Koch and only 19 years after the first meeting with the Russian researcher, in 1906, Koch publicly admitted that he was wrong. Mechnikov also worked on a vaccine against tuberculosis, typhoid fever and syphilis. He developed a prophylactic ointment, which he tested on himself, specially infected with syphilis. This ointment protected many soldiers, among whom the prevalence of the disease reached 20%. Now a number of bacteriological and immunological institutes in Russia are named after I.I. Mechnikov).

For the discovery of the phagocytic (cellular) theory of immunity, Ilya Mechnikov received the Nobel Prize in Physiology or Medicine, together with Paul Ehrlich, the author of the humoral theory of immunity.

Paul Ehrlich argued that the main role in protection against infections belongs not to cells, but to the antibodies discovered by them - specific molecules that are formed in the blood serum in response to the introduction of the aggressor. Ehrlich's theory was called the theory of humoral immunity (this is a part of the immune system that performs its function in the body's fluids - blood, interstitial fluids).

In 1908, when the scientists who opposed Mechnikov and Ehrlich were awarded the prestigious prize for two, the then members of the Nobel Committee did not even assume that their decision was visionary: both scientists were right in their theories.

They revealed only some of the key points of the "first line of defense" - the innate immune system.

Two types of immunity, their relationship

As it turned out, in nature there are two lines of defense or two types of immunity. The first is the innate immune system, which is aimed at destroying the cell membrane of a foreign cell. It is inherent in all living things - from the Drosophila flea to humans. But if, nevertheless, any foreign protein molecule managed to break through the "first line of defense", the "second line" - acquired immunity - is dealt with it. Congenital immunity is passed on to the baby during pregnancy, by inheritance.

Acquired (specific) immunity is the highest form of protection that is inherent only in vertebrates. The mechanism of acquired immunity is very complex: when a foreign protein molecule enters the body, white blood cells (leukocytes) begin to produce antibodies - a specific antibody is produced for each protein (antigen). First, the so-called T-cells (T-lymphocytes) are activated, which begin to produce active substances that trigger the synthesis of antibodies by B-cells (B-lymphocytes). The strength or weakness of the immune system is usually measured by the number of B and T cells. Then the produced antibodies "sit" on harmful proteins-antigens, which are on the surface of the virus or bacteria, and the development of infection in the body is blocked.

Like innate immunity, acquired immunity is divided into cellular (T-lymphocytes) and humoral (antibodies produced by B-lymphocytes).

The process of producing protective antibodies does not start immediately, it has a certain incubation period, depending on the type of pathogen. But if the activation process has started, then when the infection tries to re-enter the body, B-cells, which can stay in a "dormant state" for a long time, instantly react with the production of antibodies and the infection will be destroyed. Therefore, for some types of infections, a person develops immunity for the rest of his life.

The innate immune system is nonspecific and does not have a "long-term memory"; it reacts to the molecular structures that make up the cell membrane of bacteria inherent in all pathogenic microorganisms.

It is innate immunity that directs the launch and subsequent work of acquired immunity. But how does the innate immune system signal the acquired immunity system to produce specific antibodies? The 2011 Nobel Prize was awarded for addressing this key issue in immunology.

In 1973, Ralph Steinman discovered a new type of cell, which he called dendritic, since they outwardly resembled dendrites of neurons with a branched structure. Cells were found in all tissues of the human body that came into contact with the external environment: in the skin, lungs, mucous membrane of the gastrointestinal tract.

Steinman proved that dendritic cells mediate between innate and acquired immunity. That is, the "first line of defense" sends a signal through them, which activates T-cells and starts the cascade of antibody production by B-cells.

The main task of dendrocytes is to capture antigens and present them to T and B lymphocytes. They can even protrude "tentacles" through the mucosal surface to collect antigens from the outside. Having digested foreign substances, they expose their fragments on their surface and move to the lymph nodes, where they meet with lymphocytes. They inspect the presented fragments, recognize the "enemy image" and develop a powerful immune response.

Ralph Steinman was able to prove that immunity has a special "conductor". These are special sentry cells that are constantly busy looking for alien invasions into the body. Usually they are located on the skin, mucous membranes and are waiting in the wings to begin to act. Having found "aliens", dendritic cells begin to beat the drum - they send a signal to T-lymphocytes, which in turn warn other immune cells about their readiness to repel an attack. Dendritic cells can pick up proteins from pathogens and present them to the innate immune system for identification.

Further research by Steinman and other scientists showed that dendrocytes regulate the activity of the immune system, preventing attacks on the body's own molecules and the development of autoimmune diseases.

Steinman realized that the “orchestrators” of the immune system could work not only in fighting infections, but also in treating autoimmune diseases and tumors. Based on dendritic cells, he has created vaccines against several types of cancer that are undergoing clinical trials. Steinman's lab is currently working on an HIV vaccine. Oncologists also pin their hopes on them.

He himself became the main subject in the fight against cancer.

Rockefeller University claimed that Steinman's cancer treatment actually extended his life. The scientist managed to live four and a half years, despite the fact that the chances of extending life by at least a year for this type of cancer are no more than 5 percent. A week before his death, he continued to work in his laboratory, and died a few hours before the decision of the Nobel Committee to award him a prestigious prize (although, according to the rules, the Nobel Prize is not awarded posthumously, but in this case an exception was made and the scientist's family received the money) ...

The 2011 Nobel Prize was awarded not only to Ralph Steinman for the discovery of dendritic cells and their role in the activation of adaptive immunity, but also to Bruce Boitler and Jules Hoffmann for the discovery of the mechanisms of innate immunity activation.

Immunity theory

A further contribution to the theory of immunity was made by the American immunobiologist of Russian-Uzbek origin Ruslan Medzhitov, who, after graduating from Tashkent University and postgraduate studies at Moscow State University, later became a professor at Yale University (USA) and a scientific luminary in world immunology.

He discovered protein receptors on human cells and traced their role in the immune system.

In 1996, after several years of joint work, Medzhitov and Janeway made a real breakthrough. They suggested that foreign molecules should be recognized by the innate immunity using special receptors.

And they discovered these receptors that alert a branch of the immune system - T cells and B cells - that ward off attacks from pathogens and are called Toll receptors. Receptors are primarily located on phagocytic cells responsible for innate immunity.

Under high magnification of an electron microscope with a scanning attachment, numerous microvilli are visible on the surface of B-lymphocytes. On these microvilli are located the molecular size of the structure - receptors (sensitive devices) that recognize antigens - complex substances that cause an immune response in the body. This reaction consists in the formation of antibodies by cells of the lymphoid series. The number (density of location) of such receptors on the surface of B-lymphocytes is very large.

It was found that the innate immune system is embedded in the genome of the organism. For all beings on Earth, innate immunity is the main one. And only in the most "advanced" organisms on the ladder of evolution - higher vertebrates - in addition, acquired immunity develops. However, it is the innate who directs its launch and subsequent work.

Ruslan Medzhitov's works are recognized in the world. He has received a number of prestigious scientific awards, including the Shao Prize for Medicine in 2011, often referred to in academia as the "Nobel Prize of the East." This annual award is intended to honor the lifetime of "scientists, regardless of race, citizenship or religious beliefs, who have made significant discoveries in academic and scientific research and development, and whose work has had a significant positive impact on humanity." The Shao Prize has been established since 2002 under the patronage of a philanthropist with half a century of experience Shao Yifu, one of the founders of cinema in China and a number of other countries in Southeast Asia.

In many ways, we ourselves can take care of our health, having useful knowledge in this area. Subscribe to my news - interesting articles about food, plants and a healthy lifestyle.

Kazakh-Russian Medical University

CPC

On the topic: The history of the development of immunology. Immunity theory.

Made by: Sarsenova A.B.
Checked: Associate Professor M.G. Sabirova.
Department: Microbiology, Immunology with courses in epidemiology.
Faculty: Medical Prof. Business.
Group: 202 A

Almaty 2011

Content

Introduction
1. The birth of immunology
2. Formation of macrophages and lymphocytes
3. Development of cells of the immune system
4. Infection barriers
4.1 Mechanisms of the body's immunological defense
5. Inflammation as a Mechanism of Nonspecific Immunity
6. Role of T - lymphocytes in the immune response
7. Phagocytosis
8. Humoral and cellular immunity
9. Characteristic features of specific immunity
10. Cellular mechanisms of immunity
11. Effector mechanisms of immunity
12. Immunodeficiency states (IDS)
13. How the body defends itself against viruses
14. How the body defends itself against bacteria
15. Apoptosis as a means of prevention
conclusions
Conclusion
Bibliography
Application

Jenner E.

I. I. Mechnikov
Introduction

Chapter I. Organs and cells of the immune system
1. The origin of immunology
The beginning of the development of immunology dates back to the end of the 18th century and is associated with the name of E. Jenner, who for the first time applied, on the basis of only practical observations, the theoretically grounded method of vaccination against smallpox.
The fact discovered by E. Jenner formed the basis for L. Pasteur's further experiments, which culminated in the formulation of the principle of prevention against infectious diseases - the principle of immunization with weakened or killed pathogens.
The development of immunology for a long time took place within the framework of microbiological science and concerned only the study of the body's immunity to infectious agents. Along this path, great strides have been made in elucidating the etiology of a number of infectious diseases. A practical achievement was the development of methods for the diagnosis, prevention and treatment of infectious diseases, mainly through the creation of various kinds of vaccines and sera. Numerous attempts to elucidate the mechanisms that determine the resistance of the organism against the pathogen were crowned with the creation of two theories of immunity - phagocytic, formulated in 1887 by I.I.Mechnikov, and humoral, put forward in 1901 by P. Erlich.
The beginning of the 20th century is the time of the emergence of another branch of immunological science - non-infectious immunology. As the starting point for the development of infectious immunology were the observations of E. Jenner, so for the non-infectious one, the discovery by J. Bordet and N. Chistovich of the fact of the production of antibodies in the body of an animal in response to the introduction of not only microorganisms, but generally foreign agents. Non-infectious immunology received its approval and development in the doctrine of cytotoxins - antibodies against certain tissues of the body, created by I.I.Mechnikov in 1900, in the discovery of antigens of human erythrocytes by K. Landsteiner in 1901.
The results of the work of P. Medavar (1946) expanded the scope and drew close attention to non-infectious immunology, explaining that the process of rejection of foreign tissues by the body is also based on immunological mechanisms. And it was the further expansion of research in the field of transplant immunity that attracted the discovery in 1953 of the phenomenon of immunological tolerance - the non-response of the organism to the introduced foreign tissue.
I.I.Mechnikov put a phagocyte, or a cell, at the head of his system. The supporters of “humoral” immunity E. Bering, R. Koch, P. Ehrlich (Nobel Prizes of 1901, 1905 and 1908) fiercely opposed this interpretation. Latin "humor" or "humor" means liquid, in this case it meant blood and lymph. All three believed that the body protects itself from microbes with the help of special substances floating in humors. They were called "ant and toxins" and "annt and tela".
It should be noted the sagacity of the members of the Nobel Committee, who, back in 1908, tried to reconcile the two opposing theories of immunity by awarding II Mechnikov and the German Paul Ehrlich. Then the awards for immunologists fell like a cornucopia (see Appendix).
Mechnikov's student, the Belgian J. Bordet, discovered a special substance in the blood, which turned out to be a protein that helps antibodies recognize an antigen.
An t and gen and are called substances that, when they enter the body, stimulate the production of an t. In turn, antibodies are highly specific proteins. By binding to antigens (for example, bacterial toxins), they neutralize them, preventing them from destroying cells. Ant and bodies are synthesized in the body by lymphocytes or lymph cells. Limfoy Greeks called clean and transparent water of underground springs and springs. Lymph, unlike blood, is a clear, yellowish liquid. Lymphocytes are found not only in the lymph, but also in the blood. However, the penetration of antigen into the blood is still not enough for the synthesis of antibodies to begin. The antigen needs to be absorbed and processed by the phagocyte, or macrophage. Thus, the Mechnikov macrophage is at the very beginning of the body's immune response. The outline for this answer might look like this:
Antigen - Macrophage -? - Lymphocyte - Antibodies - Infectious agent
We can say that passions have been boiling around this simple scheme for a century. Immunology has become a theory of medicine and an important biological problem. This is where molecular and cell biology, genetics, evolution and many other disciplines are tied. Not surprisingly, it is immunologists who have received the lion's share of the biomedical Nobel Prizes.

2. Formation of macrophages and lymphocytes
Anatomically, the immune system appears to be fragmented. Its organs and cells are scattered throughout the body, although in fact they are all connected into a single system by blood and lymphatic vessels. The organs of the immune system are usually divided into central and peripheral. The central organs include Bone marrow and thymus, to peripheral organs - lymph nodes, spleen, lymphoid congestion(different sizes) located along the intestines, lungs, etc. (fig. 3).
Bone marrow contains stem (or germinal) cells - the ancestors of all hematopoietic cells ( erythrocytes, platelets, leukocytes, macrophages and lymphocytes). Macrophages and lymphocytes are the main cells of the immune system. Generally and briefly, it is customary to call them im mu n n o ts and t and m. The first stages of development of immunocytes take place in the bone marrow. This is their cradle.
Macrophages, they are phagocytes, - eaters of foreign bodies and the most ancient cells of the immune system. After going through several stages of development (Fig. 4), they leave the bone marrow in the form monocytes(round cells) and circulate in the blood for a certain time. From the bloodstream, they penetrate into all organs and tissues, where they change their round shape to a trimmed one. In this form, they become more mobile and able to stick to any potential "alien".
Lymphocytes today are considered to be the main figures in immunological surveillance. It is a system of cells with various functional purposes. Already in the bone marrow, the precursors of lymphocytes are divided into two large branches. One of them - in mammals - completes its development in the bone marrow, and in birds in a specialized lymphoid organ - bursa (bursa), from the Latin word bursa. Hence, these lymphocytes are called bursa-dependent, or B-lymphocytes... Another large branch of the precursors from the bone marrow migrates to another central organ of the lymphoid system - the thymus. This branch of lymphocytes is called thymus-dependent, or T-lymphocytes(the general scheme of development of cells of the immune system is shown in Fig. 4).

3. Development of cells of the immune system
B - lymphocytes, like monocytes, undergo maturation in the bone marrow, from where mature cells enter the bloodstream. B-lymphocytes can also leave the bloodstream, settling in the spleen and lymph nodes, and turn into plasma cells.
The most important event in the development of B-lymphocytes is the recombination and mutation of genes related to the synthesis of antigens (proteins from the class of immunoglobulins directed against antigens). As a result of this gene recombination, each B-lymphocyte becomes a carrier of an individual gene capable of synthesizing separate antibodies against one antigen. And since the B-population consists of many individual clones (the offspring of these antibody-producers), in the aggregate they are able to recognize and destroy the entire set of possible antigens. After genes have been formed and antibody molecules have appeared on the cell surface in the form of receptors, B-lymphocytes leave the bone marrow. For a short time, they circulate in the bloodstream, and then penetrate into the peripheral organs, as if in a hurry to fulfill their vital purpose, since the lifespan of these lymphocytes is short, only 7-10 days.
T-lymphocytes during development in the thymus are called thymocytes... The thymus is located in the chest cavity directly behind the sternum and consists of three sections. In them, thymocytes go through three stages of development and learning for immunocompetence (Fig. 5). In the outer layer (subcapsular zone), aliens from the bone marrow are contained as predecessors, pass here as it were adaptation and still lack receptors for the recognition of antigens. In the second section (cortical layer), they are under the influence of thymus (growth and differentiating) factors acquire required by the T-cell population receptors for antigens. After the transition to the third section of the thymus (medulla), thymocytes are differentiated according to their functional characteristics and become mature T cells (Fig. 6).
The acquired receptors, depending on the biochemical structure of protein macromolecules, determine their functional status. Most of the T-lymphocytes become effector cells called Killer T(from the English killer - a killer). The smaller part performs regulatory function: T-helpers(from the English helper - helpers) enhance immunological reactivity, and T-suppressors on the contrary, they weaken it. Unlike B-lymphocytes, T-lymphocytes (mainly T-helpers) with the help of their receptors are able to recognize not just someone else's, but an altered “self”, i.e. a foreign antigen must be presented (usually by macrophages) in combination with the body's own proteins. After completion of development in the thymus, part of the mature T-lymphocytes remains in the medulla, and most leave it and settle in the spleen and lymph nodes.
For a long time it remained unclear why more than 90% of the early precursors of T cells coming from the bone marrow die in the thymus. The famous Australian immunologist F. Burnet suggests that the death of those lymphocytes that are capable of autoimmune aggression occurs in the thymus. The main reason for such massive death is associated with the selection of cells that are able to react with their own antigens. All lymphocytes that have not passed the specificity control die.

4.1. Mechanisms of the body's immunological defense
Thus, even a brief excursion into the history of the development of immunology makes it possible to assess the role of this science in solving a number of medical and biological problems. Infectious immunology - the progenitor of general immunology - has now become only its branch.
It became obvious that the organism very accurately distinguishes between "its own" and "alien", and the same mechanisms underlie the reactions that arise in it in response to the introduction of foreign agents (regardless of their nature). The study of the totality of processes and mechanisms aimed at maintaining the constancy of the internal environment of the body from infections and other foreign agents - immunity, forms the basis of immunological science (V.D. Timakov, 1973).
The second half of the twentieth century was marked by the rapid development of immunology. It was during these years that the selection-clonal theory of immunity was created, the regularities of the functioning of various links of the lymphoid system as a single and integral system of immunity were revealed. One of the most important advances in recent years has been the discovery of two independent effector mechanisms in a specific immune response. One of them is associated with the so-called B-lymphocytes, carrying out a humoral response (synthesis of immunoglobulins), the other - with the system of T-lymphocytes (thymus-dependent cells), the result of which is a cellular response (accumulation of sensitized lymphocytes). It is especially important to obtain evidence of the existence of an interaction of these two types of lymphocytes in the immune response.
The research results suggest that the immunological system is an important link in the complex mechanism of adaptation of the human body, and its action is primarily aimed at maintaining antigenic homeostasis, the violation of which may be due to the penetration of foreign antigens into the body (infection, transplantation) or spontaneous mutation.
Nezelof envisioned a diagram of the mechanisms that carry out immunological protection as follows:

But, as studies of recent years have shown, the division of immunity into hummoral and cellular is very arbitrary. Indeed, the effect of the antigen on the lymphocyte and the reticular cell is carried out with the help of micro- and macrophages, which process immunological information. At the same time, the reaction of phagocytosis, as a rule, involves humoral factors, and the basis of humoral immunity is made up of cells that produce specific immunoglobulins. The mechanisms aimed at eliminating a foreign agent are extremely diverse. In this case, two concepts can be distinguished - "immunological reactivity" and "nonspecific factors of protection". The first is understood as specific responses to antigens due to the highly specific ability of the body to respond to foreign molecules. However, the body's defense against infections also depends on the degree of permeability to pathogenic microorganisms of the skin and mucous membranes, and the presence of bactericidal substances in their secrets, acidity of gastric contents, and the presence of enzyme systems such as lysozyme in biological fluids of the body. All these mechanisms refer to nonspecific factors of protection, since there is no special response and they all exist regardless of the presence or absence of the pathogen. A certain special position is occupied by phagocytes and the complement system. This is due to the fact that, despite the nonspecificity of phagocytosis, macrophages are involved in the processing of antigen and in the cooperation of T- and B-lymphocytes in the immune response, that is, they participate in specific forms of response to foreign substances. Similarly, complement production is not a specific response to an antigen, but the complement system itself is involved in specific antigen-antibody responses.

5. Inflammation as a mechanism of nonspecific immunity
Inflammation is the body's response to foreign microorganisms and tissue breakdown products. This is the main mechanism of the natural ( congenital, or non-specific) immunity, as well as the initial and final stages of immunity when acquired. Like any defense reaction, it must combine the ability to recognize a particle foreign to the body with an effective way to neutralize and remove it from the body. A classic example is inflammation caused by a splinter that has penetrated the skin and is contaminated with bacteria.
Normally, the walls of blood vessels are impermeable to blood components - plasma and corpuscles (erythrocytes and leukocytes). Increased permeability to blood plasma - due to changes in the walls of blood vessels, the formation of "gaps" between tightly adjacent endothelial cells. In the area of ​​the splinter, inhibition of the movement of erythrocytes and leukocytes (white blood cells) is observed, which begin to stick to the walls of the capillaries, forming “plugs”. Two types of leukocytes - monocytes and neutrophils - begin to actively "squeeze" from the blood into the surrounding tissue between endothelial cells in the area of ​​developing inflammation.
Monocytes and neutrophils are intended for phagocytosis - the absorption and destruction of foreign particles. Purposeful active movement to the focus of inflammation is called chemotaxis. Arriving at the site of inflammation, monocytes turn into macrophages. These are cells with tissue localization, actively phagocytizing, with a “sticky” surface, mobile, as if feeling everything that is in the immediate environment. Neutrophils also come to the site of inflammation, and their phagocytic activity increases. Phagocytic cells accumulate, actively absorb and destroy (intracellularly) bacteria and cell debris.
The activation of the three main systems involved in inflammation determines the composition and dynamics of the “actors”. They include the education system kinins, the system complement and the system activated phagocytic cells.

6. The role of T - lymphocytes in the immune response

7. Phagocytosis
The enormous role of phagocytosis not only in innate, but also in acquired immunity is becoming more and more evident thanks to the work of the last decade. Phagocytosis begins with the accumulation of phagocytes at the site of inflammation. Monocytes and neutrophils play the main role in this process. Monocytes, having come to the focus of inflammation, turn into macrophages - tissue phagocytic cells. Phagocytes, interacting with bacteria, are activated, their membrane becomes "sticky", granules filled with powerful proteases accumulate in the cytoplasm. Oxygen uptake and generation of reactive oxygen species (oxygen explosion) increase, including hydrogen peroxides and hypochlorite, as well as
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