Who discovered antibodies and created humoral ones. History of the study of immunity. Distinctive features of phagocytes

During the second half of the 19th century, doctors and biologists of that time actively studied the role of pathogenic microorganisms in the development of infectious diseases, as well as the possibility of forming artificial immunity to them. These studies led to a study of the facts about the body's natural defenses against infection. Pasteur proposed to the scientific community the idea of \u200b\u200bthe so-called "depleted power". According to this theory, viral immunity is a condition in which the human body is not a beneficial breeding ground for infectious agents. However, this idea could not explain a number of practical observations.

Mechnikov: cellular theory of immunity

This theory appeared in 1883. The creator of the cellular theory of immunity was based on the teachings of Charles Darwin and was based on the study of digestion processes in animals, which are located at various stages of evolutionary development. The author of the newly-appeared theory found some similarity in the intracellular digestion of substances in endoderm cells, amoebae, tissue macrophages and monocytes. Actually, the famous Russian biologist Ilya Mechnikov created immunity. His work in this area continued for a long time. They began in the Italian city of Messina, where a microbiologist observed the behavior of larvae.

The pathologist found that the wandering cells of the observed creatures surrounded and then absorbed foreign bodies. In addition, they dissolve and then destroy those tissues that the body no longer needs. He put a lot of effort into developing his concept. The creator of the cellular theory of immunity introduced, in fact, the concept of "phagocytes", derived from the Greek words "phages" - to eat and "kitos" - a cell. That is, the new term literally meant the process of eating cells. The scientist came to the idea of \u200b\u200bsuch phagocytes a little earlier, when he studied intracellular digestion in various cells of the connective tissue in invertebrates: sponges, amoebas and others.

In representatives of the higher animal world, the most typical phagocytes can be called white blood cells, that is, leukocytes. Later, the creator of the cellular theory of immunity proposed to divide such cells into macrophages and microphages. The correctness of this division was confirmed by the achievements of the scientist P. Ehrlich, who differentiated different types of leukocytes by means of staining. In his classic works on the pathology of inflammation, the creator of the cellular theory of immunity was able to prove the role of phagocytic cells in the elimination of pathogens. Already in 1901, his fundamental work on immunity to infectious diseases was published. In addition to Ilya Mechnikov himself, a significant contribution to the development and spread of the theory of phagocytic immunity was made by I.G. Savchenko, F. Ya. Chistovich, L.A. Tarasevich, A.M. Berezka, V.I. Isaev and a number of other researchers.

Immunology as a definite area of \u200b\u200bresearch arose from the practical need to combat infectious diseases. As a separate scientific direction, immunology was formed only in the second half of the twentieth century. The history of immunology as an applied branch of infectious pathology and microbiology is much longer. Centuries-old observations of infectious diseases laid the foundation for modern immunology: despite the widespread plague (V century BC), no one fell ill twice, at least fatally, and those who had been ill were used to bury the corpses.

There is evidence that the first smallpox vaccinations were carried out in China a thousand years before the birth of Christ. The inoculation of the contents of smallpox pustules to healthy people in order to protect them from the acute form of the disease then spread to India, Asia Minor, Europe, and the Caucasus.

Inoculation was replaced by the vaccination method (from the Latin “vacca” - cow), developed at the end of the 18th century. English doctor E. Jenner... He drew attention to the fact that thrush women caring for sick animals sometimes fell ill in an extremely mild form of smallpox of cows, but never got sick with smallpox. Such an observation gave the researcher a real opportunity to combat the disease of people. In 1796, 30 years after the beginning of his research, E. Jenner decided to test the vaccination method with vaccinia. The experiment was successful and since then the method of vaccination according to E. Jenner has found wide application throughout the world.

The origin of infectious immunology is associated with the name of an outstanding French scientist Louis Pasteur... The first step towards a targeted search for vaccine preparations that create a stable immunity to infection was made after Pasteur's observation of the pathogenicity of the pathogen of chicken cholera. From this observation, Pasteur concluded that an aged culture, having lost its pathogenicity, remains capable of creating resistance to infection. This determined for many decades the principle of creating a vaccine material - in one way or another (for each pathogen its own) to achieve a decrease in the virulence of the pathogen while maintaining its immunogenic properties.
Although Pasteur developed the principles of vaccination and applied them successfully in practice, he was not aware of the factors involved in protecting against infection. The first to shed light on one of the mechanisms of resistance to infection were Emil von Bering and Kitazato... They demonstrated that serum from mice previously immunized with tetanus toxin, injected into intact animals, protected the latter from a lethal dose of the toxin. The serum factor, antitoxin, formed as a result of immunization, was the first specific antibody found. The work of these scientists laid the foundation for the study of the mechanisms of humoral immunity.
The Russian evolutionary biologist was at the origin of the knowledge of cellular immunity Ilya Ilyich Mechnikov... In 1883, he made the first report on the phagocytic theory of immunity at the congress of physicians and naturalists in Odessa. A person has amoeboid motile cells - macrophages, neutrophils. They "eat" food of a special kind - pathogenic microbes, the function of these cells is to fight microbial aggression.
In parallel with Mechnikov, a German pharmacologist was developing his theory of immune protection against infection Paul Ehrlich... He knew about the fact that in the blood serum of animals infected with bacteria, proteins appear that can kill pathogenic microorganisms. These substances were later called "antibodies" by him. The most characteristic property of antibodies is their pronounced specificity. Having formed as a protective agent against one microorganism, they neutralize and destroy only it, remaining indifferent to others.
Two theories - phagocytic (cellular) and humoral - at the time of their emergence stood on antagonistic positions. The schools of Mechnikov and Ehrlich fought for scientific truth, unaware that every blow and every parry of it brought opponents closer together. In 1908, both scientists were simultaneously awarded the Nobel Prize.
By the end of the 40s - the beginning of the 50s of the twentieth century, the first period of the development of immunology ends. A whole arsenal of vaccines has been created against the widest range of infectious diseases. Plague, cholera and smallpox epidemics have ceased to kill hundreds of thousands of people. Individual, sporadic outbreaks of these diseases are still encountered, but these are only very local cases that do not have epidemiological, and even more so pandemic, cases.


Figure: 1. Scientists-immunologists: E. Jenner, L. Pasteur, II. Mechnikov, P. Erlich.

A new stage in the development of immunology is associated primarily with the name of the outstanding Australian scientist M.F. Burnet... It was he who largely defined the face of modern immunology. Considering immunity as a reaction aimed at differentiating everything “us” from everything “foreign”, he raised the question of the importance of immune mechanisms in maintaining the genetic integrity of the organism during the period of individual (ontogenetic) development. It was Burnet who drew attention to the lymphocyte as the main participant in a specific immune response, giving it the name "immunocyte". It was Burnet who predicted, and the Englishman Peter Medawar and Czech Milan Hasek experimentally confirmed a state opposite to immune reactivity - tolerance. It was Burnet who pointed out the special role of the thymus in the formation of the immune response. And, finally, Burnet remained in the history of immunology as the creator of the clonal selection theory of immunity. The formula for this theory is simple: one clone of lymphocytes is capable of responding to only one specific, antigenic, specific determinant.
Particularly noteworthy are Burnet's views on immunity as such a reaction of the body that distinguishes everything “ours” from everything “foreign”. After Medavar proved the immunological nature of the rejection of a foreign transplant, after the accumulation of facts on the immunology of malignant neoplasms, it became obvious that the immune response develops not only to microbial antigens, but also when there are any, albeit insignificant, antigenic differences between the organism and that biological material (transplant, malignant tumor) with which he meets.

Today we know, if not all, then many of the mechanisms of the immune response. We know the genetic basis of a surprisingly wide variety of antibodies and antigen-recognizing receptors. We know which cell types are responsible for the cellular and humoral forms of the immune response; the mechanisms of increased reactivity and tolerance are largely understood; much is known about the processes of antigen recognition; identified molecular participants in intercellular relationships (cytokines); in evolutionary immunology, the concept of the role of specific immunity in the progressive evolution of animals has been formed. Immunology, as an independent branch of science, has risen on a par with the truly biological disciplines: molecular biology, genetics, cytology, physiology, evolutionary doctrine.


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 some diseases twice. So, back in the IV 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 typhoid, 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 infection of a person 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 smallpox infections.

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 Behring reported that after introducing into the body of an animal not whole diphtheria bacteria, but only 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 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 it 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 resembles a "slingshot" (Fig. 2). The part of an antibody molecule that binds to an antigen is highly 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 will come to their aid and, first of all, special "eater cells".

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.

In 1908 Ilya Ilyich Mechnikov and Paul Ehrlich became Nobel laureates for their work on immunology, and they are rightly considered the founders of the science of the body's defenses.

II Mechnikov was born in 1845 in the Kharkov province and graduated from Kharkov University. However, the most significant scientific research Mechnikov conducted abroad: for more than 25 years he worked in Paris, at the famous Pasteur Institute.

Investigating the digestion of a starfish larva, the scientist discovered that it has special mobile cells that absorb and digest food particles.

  • Immunity. Types of immunity;
  • Types of immunity;
  • Immunization;
  • Defense mechanisms of the body's cellular homeostasis.

Mechnikov suggested that they also "serve in the body to counteract harmful agents." The scientist called these cells phagocytes. Phagocyte cells were found by Mechnikov in the human body. Until the end of his life, the scientist developed the phagocytic theory of immunity, investigating human immunity to tuberculosis, cholera and other infectious diseases. Mechnikov was an internationally recognized scientist, an honorary academician of six academies of sciences. He died in 1916 in Paris.

At the same time, the problems of immunity were studied by a German scientist Paul Ehrlich (1854-1915). Ehrlich's hypotheses formed the basis of the humoral theory of immunity. He suggested that in response to the appearance of a toxin that a bacterium produces, or, as they say today, an antigen, an antitoxin is formed in the body - an antibody that neutralizes the aggressor bacterium. In order for certain cells in the body to start producing antibodies, the antigen has to recognize receptors on the cell surface. Ehrlich's ideas found their experimental confirmation after a decade.

Paul Ehrlich

Mechnikov and Ehrlich created various theories, but none of them sought to defend only their own point of view. They saw that both theories were correct. Now it has been proven that both immune mechanisms are actually working in the body - both Mechnikov's phagocytes and Ehrlich's antibodies.

The internal environment of the human body is made up of blood, tissue fluid and lymph. Blood performs transport and protective functions. It consists of liquid plasma and corpuscles: erythrocytes, leukocytes and platelets.

Red blood cells containing hemoglobin are responsible for the transport of oxygen and carbon dioxide. Platelets, together with plasma substances, provide blood clotting. Leukocytes are involved in the creation of immunity.

Distinguish between nonspecific innate and specific acquired immunity; in each of the types of immunity, cellular and humoral links are distinguished.

Due to lymph and blood, the constancy of the volume and chemical composition of tissue fluid is maintained - the environment in which the cells of the body function.

Tags: Ilya Ilyich Mechnikov Immunity Paul Ehrlich

theory of immunity - Which scientist is considered the creator of the cellular theory of immunity? - 2 answers

The cellular theory of immunity created

In the section Schools to the question Which scientist is considered the creator of the cellular theory of immunity? given by the author Irina Munitsyna the best answer is The first to shed light on one of the mechanisms of resistance to infection were Behring and Kitasato, who demonstrated that serum from mice pre-immunized with tetanus toxin administered to intact animals protects the latter From a lethal dose of toxin. The serum factor formed as a result of immunization - antitoxin - was the first discovered specific antibody. The work of these scientists laid the foundation for the study of the mechanisms of humoral immunity. Russian evolutionary biologist Ilya Mechnikov was at the origins of the knowledge of cellular immunity. In 1883, he made the first report on the phagocytic (cellular) theory of immunity at the congress of physicians and naturalists in Odessa. Mechnikov then argued that the ability of mobile cells of invertebrates to absorb food particles, ie, to participate in digestion, is in fact their ability to absorb in general everything "foreign" that is not characteristic of the body: various microbes, inert particles, dying body parts. A person also has amoeboid motile cells - macrophages and neutrophils. But they "eat" food of a special kind - pathogenic microbes.

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Answer from LANA The Russian evolutionary biologist Ilya Mechnikov was the origin of the knowledge of cellular immunity. In 1883, he made the first report on the phagocytic (cellular) theory of immunity at the congress of doctors and natural scientists in Odessa. Mechnikov then argued that the ability of mobile cells of invertebrates to absorb food particles, ie, to participate in digestion, is actually their ability to absorb in general everything "foreign" that is not characteristic of the body: various microbes, inert particles, dying body parts. A person also has amoeboid motile cells - macrophages and neutrophils. But they "eat" food of a special kind - pathogenic microbes. Evolution has retained the absorption capacity of amoeboid cells from unicellular animals to higher vertebrates, including humans. However, the function of these cells in highly organized multicellular organisms has become different - it is the fight against microbial aggression. In parallel with Mechnikov, the German pharmacologist Paul Ehrlich was developing his theory of immune protection against infection. He knew about the fact that in the blood serum of animals infected with bacteria, proteins appear that can kill pathogenic microorganisms. These substances were later called "antibodies" by him. The most characteristic property of antibodies is their pronounced specificity. Having formed as a protective agent against one microorganism, they neutralize and destroy only it, remaining indifferent to others. Trying to understand this phenomenon of specificity, Ehrlich put forward the theory of "side chains", according to which antibodies in the form of receptors pre-exist on the surface of cells. In this case, the antigen of microorganisms acts as a selective factor. Coming into contact with a specific receptor, it provides enhanced production and circulation of only this specific receptor (antibody). Ehrlich's perspicacity is striking, since with some changes this generally speculative theory has now been confirmed. Two theories - cellular (phagocytic) and humoral - at the time of their emergence stood on antagonistic positions. The schools of Mechnikov and Ehrlich fought for scientific truth, unaware that every blow and every parry of it brought opponents closer together. In 1908. both scientists were simultaneously awarded the Nobel Prize. A new stage in the development of immunology is associated primarily with the name of the outstanding Australian scientist M. Burnet (Macfarlane Burnet; 1899-1985). It was he who largely determined the face of modern immunology. Considering immunity as a reaction aimed at differentiating everything “us” from everything “foreign”, he raised the question of the importance of immune mechanisms in maintaining the genetic integrity of the organism during the period of individual (ontogenetic) development. It was Burnett who drew attention to the lymphocyte as the main participant in a specific immune response, giving it the name “immunocyte”. It was Burnet who predicted, and the Englishman Peter Medavar and the Czech Milan Hasek experimentally confirmed the state opposite to immune reactivity - tolerance. It was Burnet who pointed out the special role of the thymus in the formation of the immune response. And finally, Burnet remained in the history of immunology as the creator of the clonal selection theory of immunity (Fig. C.9). The formula for this theory is simple: one clone of lymphocytes is capable of responding to only one specific antigenic specific determinant.

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Development of the Science of Immunity | Meddoc

Immunology is the science of the body's defenses aimed at preserving its structural and functional integrity and biological identity. 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.

Edward Jenner

Making vaccines

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 of cattle was called "cowpox"), and on their udders are formed bubbles strongly resembling 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 too.

In 1796, Jenner inoculated a liquid taken from the pock marks of cows into a healthy eight-year-old boy. He 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.

Louis Pasteur

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 suffer. The sick person develops hydrophobia - it is impossible to drink, since the water causes cramps in the pharynx and larynx. Death can occur as a result of 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.

Ilya Ilyich Mechnikov

In 1890, the German bacteriologist Emil von Bering (1854-1917) established that in response to the introduction of microbes and their poisons, protective substances - antibodies - are produced in the body. 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.

Articles: History of the fight against smallpox. Vaccination | Immunological centers in Kiev

Pasteur did not know why vaccinations protect against infectious diseases. He thought that microbes "eat away" from the body something they need.

Pasteur did not know why vaccinations protect against infectious diseases. He thought that microbes "eat away" from the body something they need.

Who revealed the mechanisms of immunity?

Ilya Ilyich Mechnikov and Paul Ehrlich. They also created the first theories of immunity. The theories are very opposite. Scientists have had to argue all their lives.

In that case, maybe they are the creators of the science of immunity, and not Pasteur?

Yes they. But the father of immunology is Pasteur.

Pasteur discovered a new principle, he discovered a phenomenon, the mechanisms of which are still being studied. Just like Alexander Fleming is the father of penicillin, although when he discovered it, he knew nothing about its chemical structure and mechanism of action. The decryption came later. Now penicillin is synthesized in chemical plants. But the father is Fleming. Konstantin Eduardovich Tsiolkovsky is the father of rocket navigation. He substantiated the main principles. The first Soviet satellites in the world, and then the American ones, launched by other people, after the death of the father of rocket navigation, did not overshadow the significance of his work.

“From the earliest to the most recent times, it was taken for certain that the organism possesses some kind of ability to react against harmful influences entering it from the outside. This ability to resist has been called variously. Mechnikov's studies quite firmly establish the fact that this ability depends on the properties of phagocytes, mainly white blood cells and connective tissue cells, to devour microscopic organisms that enter the body of a higher animal. " So told the magazine "Russian Medicine" about the report of Ilya Ilyich Mechnikov in the Society of Kiev Doctors, made on January 21, 1884.

Of course not. The report formulated thoughts that were born in the scientist's head much earlier, during his work. By that time, some elements of the theory had already been published in articles and reports. But you can call this date the birthday of the great debate on the theory of immunity.

The discussion lasted 15 years. A brutal war in which the colors of one point of view were on the banner raised by Mechnikov. The colors of another banner were defended by such great knights of bacteriology as Emil Bering, Richard Pfeiffer, Robert Koch, Rudolf Emmerich. Paul Ehrlich, the author of a fundamentally different theory of immunity, led them in this struggle.

Mechnikov and Ehrlich's theories excluded one another. The dispute was conducted not behind a closed door, but in front of the whole world. At conferences and congresses, on the pages of magazines and books, the next experimental attacks and counter-attacks of opponents were crossed everywhere. The weapon was facts. Just the facts.

The idea was born suddenly. At night. Mechnikov sat alone at his microscope and observed the life of mobile cells in the body of the transparent larvae of sea stars. He recalled that it was on that evening, when the whole family went to the circus, and he stayed to work, a thought struck him. The idea that these motile cells must be related to the body's defense. (Probably, this should be considered a "moment of birth".)

Dozens of experiments followed. Foreign particles - a splinter, paint grains, bacteria - are captured by mobile cells. Under the microscope, cells can be seen gathering around uninvited aliens. Part of the cage stretches out in the form of a cape - a false leg. In Latin they are called "pseudopodia". Foreign particles are covered by pseudopodia and find themselves inside the cell, as if devoured by it. Mechnikov called these cells phagocytes, which means eater cells.

He found them in a wide variety of animals. In starfish and worms, in frogs and rabbits, and, of course, in humans. All representatives of the animal kingdom have specialized phagocyte cells in almost all tissues and blood.

The most interesting thing, of course, is bacterial phagocytosis.

Here the scientist introduces anthrax pathogens into the tissues of the frog. Phagocytes flock to the place of introduction of microbes. Each captures one, two, or even a dozen bacilli. The cells devour these sticks and digest them.

So here it is, the mysterious mechanism of immunity! This is how the fight against pathogens of infectious diseases goes. Now it is clear why one person gets sick during an epidemic of cholera (and not only cholera!), And the other does not. This means that the main thing is the number and activity of phagocytes.

At the same time, in the early eighties, scientists in Europe, especially Germany, deciphered the mechanism of immunity in a slightly different way. They believed that microbes in the body are destroyed not by cells at all, but by special substances in the blood and other body fluids. The concept was called humoral, that is, liquid.

And the dispute began ...

1887 year. International Hygiene Congress in Vienna. Mechnikov's phagocytes and his theories are spoken of only incidentally, as something completely improbable. The Munich bacteriologist, a student of the hygienist Max Pettenkofer, Rudolf Emmerich in his report says that he injected immune, that is, previously vaccinated pigs with a rubella microbe, and the bacteria died within an hour. They died without any intervention of phagocytes, which during this time did not even have time to "swim" to the microbes.

What is Mechnikov doing?

He does not scold his opponent, does not write pamphlets. He formulated his phagocytic theory before he saw the consumption of rubella microbes by cells. He does not call on authorities for help. It reproduces Emmerich's experience. The Munich colleague was wrong. Even after four hours, the germs are still alive. Mechnikov reports the results of HIS experiments to Emmerich.

Emmerich repeats the experiments and becomes convinced of his mistake. Rubella germs die in 8-10 hours. And this is exactly the time that phagocytes need to work. In 1891, Emmerich publishes self-refuting articles.

1891 year. Another international hygiene congress. Now he is going to London. Emil Bering, also a German bacteriologist, joins the discussion. Bering's name will forever remain in people's memory. It is associated with a discovery that saved millions of lives. Bering is the creator of the anti-diphtheria serum.

A follower of the humoral theory of immunity, Bering made a very logical assumption. If an animal has suffered some infectious disease in the past and has developed immunity, then the blood serum, its acellular part, must increase its bactericidal force. If this is the case, then microbes, weakened or in small quantities, can be artificially introduced to animals.

You can artificially develop such immunity. And the serum of this animal must kill the corresponding microbes. Bering created an anti-tetanus serum. To get it, he injected rabbits with tetanus bacillus poison, gradually increasing its dose. And now we need to test the strength of this serum. Infect a rat, rabbit or mouse with tetanus, and then inject anti-tetanus serum, the blood serum of the immunized rabbit.

The disease did not develop. The animals remained alive. Bering did the same with diphtheria rods. And this is how diphtheria began to be treated in children and is still treated using serum from previously immunized horses. In 1901, Bering received the Nobel Prize for this.

But what does the eater cells have to do with it? Serum was injected, a part of the blood where there are no cells. And the serum helped fight germs. No cells, no phagocytes entered the body, and nevertheless it received some kind of weapon against microbes. Therefore, cells have nothing to do with it. There is something in the cell-free part of the blood. Hence, the humoral theory is correct. The phagocytic theory is wrong.

As a result of such a blow, the scientist gets an impetus to new work, to new research. Begins ... or rather, the search continues, and, naturally, Mechnikov again responds with experiments. As a result, it turns out that serum does not kill the causative agents of diphtheria and tetanus. It neutralizes toxins and poisons secreted by them, and stimulates phagocytes. Serum-activated phagocytes easily deal with disarmed bacteria, whose poisonous secretions are neutralized by antitoxins in the same serum, that is, antidotes.

The two theories are starting to converge. Mechnikov still convincingly proves that phagocytes play the main role in the fight against microbes. After all, in the end, all the same, the phagocyte takes the decisive step and devours microbes. Nevertheless, Mechnikov is forced to accept some elements of the humoral theory.

Humoral mechanisms in the fight against microbes still work, they exist. After Bering's studies, we have to agree that contact of the body with microbial bodies leads to the accumulation of antibodies circulating in the blood. (A new concept has appeared - an antibody; more on antibodies will be further.) Some microbes, such as cholera vibrios, die and dissolve under the influence of antibodies.

Does this cancel the cell theory? In no case. After all, antibodies must be produced, like everything else in the body, by cells. And of course, phagocytes are responsible for the main job of capturing and killing bacteria.

1894 year. Budapest. Another international congress. And again Mechnikov's passionate polemic, but this time with Pfeiffer. The cities changed, the topics discussed in the dispute changed. The discussion pushed deeper and deeper into the complex relationship of animals with microbes.

The intensity of the controversy, the passion and the intensity of the controversy remained the same. 10 years later, on the anniversary of Ilya Ilyich Mechnikov, Emil Roux recalled these days:

“To this day, I still see you at the Budapest Congress of 1894 arguing against your opponents: your face is burning, your eyes are sparkling, your hair is tangled. You sounded like a demon of science, but your words, your irrefutable arguments, were applauded by the audience. New facts, which at first seemed to contradict the phagocytic theory, soon came into harmonious combination with it. "

That was the argument. Who won it? All! Mechnikov's theory became coherent and all-embracing. The humoral theory has found its main acting factors - antibodies. Paul Ehrlich, combining and analyzing the data of the humoral theory, created in 1901 the theory of the formation of antibodies.

15 years of dispute. 15 years of mutual refutations and clarifications. 15 years of dispute and mutual assistance.

1908 year. The highest recognition for a scientist - the Nobel Prize was awarded simultaneously to two scientists: Ilya Mechnikov, the creator of the phagocytic theory, and Paul Ehrlich, the creator of the theory of antibody formation, that is, the humoral part of the general theory of immunity. Opponents throughout the war went forward in one direction. Such a war is good!

Mechnikov and Ehrlich created the theory of immunity. They argued and won. Everyone was right, even those who seemed to be wrong. Science won. Humanity has won. In a scientific debate, everyone wins!

Next chapter\u003e

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Immunity Theory - Chemist's Handbook 21

The Russian evolutionary biologist Ilya Mechnikov was at the origin of the knowledge of the issues of cellular immunity. In 1883, he made the first report on the phagocytic theory of immunity at the congress of physicians and naturalists in Odessa. Mechnikov then argued that the ability of motile cells of invertebrates to absorb food particles, i.e. participate in digestion, there is actually their ability to absorb in general all chu-6

A model theory of immunity is outlined in 17.10.

The development of scientific microbiology in Russia was facilitated by the work of I.I.Mechnikov (1845-1916). The phagocytic theory of immunity developed by him and the doctrine of the antagonism of microorganisms contributed to the improvement of methods for combating infectious diseases.

BERNET F. The integrity of the organism (new theory of immunity). Cambridge, 1962, translated from English, 9th ed. l., price 63 kopecks.

The second fundamental theory, brilliantly confirmed by practice, was II Mechnikov's phagocytic theory of immunity, developed in 1882-1890. The essence of the doctrine of phagocytosis and phagocytes was outlined earlier. Here it is only appropriate to emphasize that it was the foundation for the study of cellular immunity and, in fact, created the prerequisites for the formation of an understanding of the cellular-humoral mechanisms of immunity.

Back in 1882, II Mechnikov discovered the phenomenon of phagocytosis and developed the cellular theory of immunity. Over the past century, immunology has become a separate biological discipline, one of the growth points of modern biology. Immunologists have shown that lymphocytes are able to destroy both foreign cells that have entered the body, and some of their own cells that have changed their properties, for example, cancer cells or cells affected by viruses. But until recently it was not known exactly how lymphocytes do this. Recently it became clear.

The existence on the surface of cells of proteins capable of selectively binding various substances from the environment surrounding the cell was predicted at the beginning of the century by Paul Ehrlich. This assumption formed the basis of his famous theory of side chains - one of the first theories of immunity, far ahead of its time. Later, hypotheses were repeatedly expressed about the existence of receptors of various specificity on cells, but it took many years before the existence of receptors was experimentally proved and their detailed study began.

Analyzing various theories of immunity, the authors show the leading role of oxidative processes in plant defense reactions. The book shows that shifts in the work of the enzymatic apparatus of the cell are a consequence of the effect of the pathogen on the activity of all the most important centers of cell activity, including the nuclear apparatus, ribosomes, mitochondria and chloroplasts.

The work of this complex and surprisingly expedient mechanism has long worried researchers. Since the time of the dispute between Mechnikov (a supporter of the cellular theory of immunity) and Ehrlich (an adherent of the humoral, serum theory), in which, as usual, both were right (and both were simultaneously awarded the Nobel Prize), and to this day, a huge number of various theories have been proposed and discussed immunity. And this is not surprising, since the theory should consistently explain a wide range of phenomena, the dynamics of accumulation of antibodies in the blood with a maximum falling on the 7-10th day, and immune memory - a faster and more significant response to the reappearance of the same antigen tolerance of high and low doses , i.e., the absence of a reaction at very low and very high concentrations of antigen, the possibility of distinguishing oneself from another, i.e., the absence of a reaction to the host's tissues, and autoimmune diseases, when such a reaction still occurs immunological reactivity in cancer and insufficient immunity when cancer can slip out of control.

The creator of the cellular theory of immunity is II Mechnikov, who in 1884 published a paper on the properties of phagocytes and the role of these cells in the immunity of organisms to bacterial infections. Almost simultaneously, the so-called humoral theory of immunity emerged, independently developed by a group of European scientists. Proponents of this theory explained the immunity by the fact that bacteria cause the formation of special substances in the blood and other body fluids, leading to the death of bacteria when they re-enter the body. In 1901, P. Ehrlich, having analyzed and generalized the data accumulated by the humoral trend, created a theory of the formation of antibodies. Many years of fierce polemics between I.I.Mechnikov and a group of the most prominent microbiologists of that time led to a comprehensive verification of both theories and their complete confirmation. In 1908, the Nobel Prize in Medicine was awarded to II Mechnikov and P. Ehrlich as the creators of the general theory of immunity.

In 1879, while studying chicken cholera, L. Pasteur developed a method for obtaining cultures of microbes that lose the ability to be the causative agent of the disease, that is, lose virulence, and used this discovery to protect the body from subsequent infection. The latter formed the basis for the creation of the theory of immunity, that is, the body's immunity to infectious diseases.

Discovery of mobile genetic elements Development of clonal selection theory of immunity Development of methods for obtaining myoclial antibodies using hybridomas Disclosure of the mechanism of regulation of cholesterol metabolism in the body Discovery and study of growth factors of cells and organs

Arrhenius sent copies of his dissertation to other universities, and Ostwald in Riga and Van't Hoff in Amsterdam praised it. O tvaJID visited Arrhenius and offered him a position at his university. This support and the resulting experimental confirmation of Arrhenius's theory changed the attitude towards him at home. Arrhenius was invited to lecture in physical chemistry at Uppsala University. Loyal to his country, he also turned down proposals from Gressen and Berlin and eventually became president of the Physicochemical Institute of the Nobel Committee. Arrhenius launched a large research program in the field of physical chemistry. His interests covered such distant problems as lightning bolts, the influence of atmospheric CO2 on glaciers, space physics and the theory of immunity to various diseases.

P. Ehrlich - German chemist - put forward the humoral (from the Latin. Humor - liquid) theory of immunity. He believed that immunity arises as a result of the formation of antibodies in the blood that neutralize the poison. This was confirmed by the discovery of antitoxins - antibodies that neutralize toxins in animals that were injected with diphtheria or tetanus

This central position of the clonal selection theory of immunity has caused great discussions for many years. It was clear that it was preterminated to the antigens that the organism encountered during phylogenesis, but doubts arose whether there really were T-lymphocytes with receptors for new (synthetic and chemical) antigens, the emergence of which in nature is associated with the development of technological progress in the XX century. However, special studies carried out using the most sensitive serological methods revealed normal antibodies to a number of chemical haptens in humans and in more than 10 mammalian species - dinitrophenyl, 3-iodine-4-hydroxyphenylacetic acid, etc. Apparently, the three-dimensional structures of receptors are indeed very diverse, and there can always be several cells in the body, the receptors of which are close enough to the new determinant. It is possible that the final grinding of the receptor to the determinant can occur after their connection during the differentiation of Tr-lymphocytes into Tr-lymphocytes, after meeting with its antigen Tr-cell, by one or two divisions, the cell turns into an antigen-recognizing and activated (committed, primed according to the terminology of different authors ) antigen of a long-lived Tg cell. Tg-lymphocytes are capable of recirculation, can re-enter the thymus, are sensitive to the action of anti-0-, anti-thymocyte and anti-lymphocyte sera. These lymphocytes are the centerpiece of the immune system. After the formation of a clone, i.e., reproduction by division into morphologically identical, but functionally heterogeneous cells, T-lymphocytes are actively involved in the formation of the immune response.

An even more complete system of equations covering almost all aspects of the modern theory of immunity (interaction of B-lymphocytes with T-helpers, T-suppressors, etc.) can be found in the works of Alperin and Isavina. A large number of parameters, many of which cannot be measured in principle, reduce, in our opinion, the heuristic value of these models. Much more interesting is the attempt of the same authors to describe the dynamics of autoimmune diseases by a second-order system with a delay. A detailed model for describing cooperative effects in immunity, containing seven equations, is contained in the work of Verigo and Skotnikova.

Despite the successes of infectious immunology, experimental and theoretical immunology remained in an embryonic state by the middle of the century. Two theories of immunity - cellular and humoral - have only lifted the curtain over the unknown. The subtle mechanisms of immune reactivity, the biological range of action of the immune system remained unclear from the researcher.

A new stage in the development of immunology is associated primarily with the name of the prominent Australian scientist M.F. Burnet. It was he who largely determined the face of modern immunology. Considering immunity as a reaction aimed at differentiating everything that is self from everything that is alien, he raised the question of the importance of immune mechanisms in maintaining the genetic integrity of the organism during the period of individual (ontogenetic) development. It was Vernet who drew attention to the lymphocyte as the main participant in the specific immune response, giving it the name immunocyte. It was Vernet who predicted, and the Englishman Peter Medavar and the Czech Milan Hasek experimentally confirmed the state opposite to immune reactivity - tolerance. It was Vernet who pointed out the special role of the thymus in the formation of the immune response. And finally. Vernet remained in the history of immunology as the creator of the clonal selection theory of immunity. The formula for this theory is simple, one clone of lymphocytes is capable of reacting only to one specific, antigenic, specific determinant.

This theory is the first selective theory of immunity. On the surface of a cell that is capable of forming antibodies, there are side chains that are complementary to the injected plow antigen. The interaction of the antigen with the side chain leads to its blockade and, as a consequence, to compensatory increased synthesis and release of the corresponding chains into the intercellular space, which increase the function of antibodies

Ehrlich suggested that the combination of an antigen with an already existing receptor on the surface of a B cell (now known to be a membrane bound immunoglobulin) causes it to synthesize and secrete an increased number of such receptors. Although, as shown in the figure, Ehrlich believed that one cell is capable of producing antibodies that bind more than one type of antigen, nevertheless he anticipated both the clonal selection theory of immunity and the fundamental idea of \u200b\u200bthe existence of receptors for an antigen even before the immune systems.

In the immunological period of the development of microbiology, a number of theories of immunity were created: P. Ehrlich's humoral theory, II Mechnikov's phagocytic theory, N. Erne's theory of idiotypic interactions, pituitary-hypothalamic-adrenal body

In the years that followed, immunological reactions and tests with phagocytes and antibodies were described and tested, and the mechanism of interaction with antigens (foreign agent substances) was clarified. In 1948 A. Fagreus proved that antibodies are synthesized by plasma cells. The immunological role of B- and T-lymphocytes was established in 1960-1972, when it was proved that under the influence of antigens, B-cells are transformed into plasma cells, and several different subpopulations arise from undifferentiated T-cells. In 1966, cytokines of T-lymphocytes were discovered, which condition the cooperation (interaction) of immunocompetent cells. Thus, the cellular-humoral theory of Mechnikov-Ehrlich immunity received a comprehensive justification, and immunology - the basis for a deep study of the specific mechanisms of certain types of immunity.

The subsequent post-Pasteur years of the development of immunology were very intense. In 1886, Daniel Salmon and Theobald Smith (USA) showed that the state of immunity causes the introduction of not only live, but also killed microbes. Inoculation of warmed-up bacilli, the causative agents of pig cholera, to pigeons caused a state of immunity to the virulent culture of microbes. Moreover, they suggested that the state of immunity can also be caused by the introduction into the body of chemical substances or toxins produced by bacteria and causing the development of the disease. In the coming years, these assumptions were not only confirmed, but also developed. In 1888, the American bacteriologist George Nettall first described the antibacterial properties of blood and other body fluids. The German bacteriologist Hans Buchner continued these studies and named alexin the heat-sensitive bactericidal factor of acellular serum, later named by Ehrlich and Morgenroth as complement. Employees of the Pasteur Institute (France) Emile Py and Alexander Yersin found that the cell-free filtrate of the culture of diphtheria bacillus contains an exotoxin that can induce disease. In December 1890, Karl Frenkel published his observations indicating the induction of immunity using a heat-killed broth culture of diphtheria bacillus. In December of the same year, the works of the German bacteriologist Emil von Bering and the Japanese bacteriologist and researcher Shibasaburo Kitasato were published. The works showed that the serum of rabbits and mice receiving tetanus toxin, or of a person who had had diphtheria, not only had the ability to inactivate a specific toxin, but also created a state of immunity when transferred to another organism. An immune serum with such properties was called antitoxic. Emil von Behring was the first researcher to be awarded the Nobel Prize for the discovery of the medicinal properties of antitoxic sera. These works were the first to open the world to the phenomenon passive immunity... As T.I. Ulyankina, "the treatment of diphtheria with antitoxin has become the second (post-Pasteur) triumph of applied immunology."
In 1898, another Nobel laureate, Jules Bordet, a Belgian bacteriologist and immunologist who received an award in 1919 for the discovery of complement, established new facts. He showed that the factors that appear in the blood of infected animals and specifically sticky infections are found in the blood of animals immunized not only with microbes or their toxin products, but also in the blood of animals that were injected with non-infectious antigens, for example, sheep erythrocytes. The serum of a rabbit that received ram erythrocytes glued only ram erythrocytes, but not human or other animal erythrocytes.
Moreover, it turned out that such gluing factors (in 1891 they were named by P. Ehrlich antibodies) can also be obtained by injecting foreign serum proteins under the skin or into the bloodstream. This fact was established by a therapist, infectious disease specialist and microbiologist, a student of I. Mechnikov and R. Koch, Nikolay Yakovlevich Chistovich... The works of I.I. Mechnikov, who discovered phagocytes in 1882, J. Bordet and N. Chistovich were the first to give rise to the development non-infectious immunology... In 1899 L. Detre, employee I.I. Mechnikov, introduced the term "antigen" to refer to substances that induce the formation of antibodies.
The German scientist Paul Ehrlich made a huge contribution to the development of immunology. In 1908 he was awarded the Nobel Prize for the discovery of humoral immunity at the same time Ilya Ilyich Mechnikov (Fig. 4), who discovered cellular immunity: the phenomenon of phagocytosis is an active response of the host in the form of a cellular reaction aimed at destroying a foreign body.

Figuratively speaking, the discoveries of P. Ehrlich and L.I. Mechnikov, immunology was likened to a tree that gave rise to two powerful independent scientific branches of knowledge, one of which is called "humoral immunity", and the other - "cellular immunity".

The name of P. Ehrlich is also associated with a host of other discoveries that have survived to this day. Thus, mast cells and eosinophils were discovered by them; the concepts of "antibody", "passive immunity", "minimum lethal dose", "complement" (together with Yu. Morgenroth), "receptor" were introduced; a titration method aimed at studying the quantitative relationships of antibodies and antigens has been developed.

P. Ehrlich (Fig. 5) put forward the dualistic concept of hematopoiesis, according to which he proposed to distinguish between lymphoid and myeloid hematopoiesis; together with J. Morgenroth in 1900, on the basis of erythrocyte antigens of goats, he described their blood groups. He found that immunity is not inherited because non-immune offspring are born to immune parents; developed the theory of "side chains", which later became the basis of breeding theories of immunity; together with K). Morgenroth undertook to study the reactions of the organism to its own cells (study of the mechanisms of autoimmunity); substantiated the presence of anti-antibodies.

The successes achieved in understanding the phenomena of immunity, discoveries, brilliant conclusions and findings did not go unnoticed. They were a powerful stimulus for the further development of immunology.

In 1905, the Swedish physical chemist Svante August Arrhenius, in his lectures on the chemistry of immunological reactions at the University of California at Berkeley, introduced the term

"Immunochemistry" ... In studies on the interaction of diphtheria toxin with antitoxin, he discovered the reversibility of the antigen-antibody immunological reaction. These observations were developed by him in the book "Immunochemistry", written in 1907, which gave the name to a new section of immunology.

Gaston Ramon, an employee of the Pasteur Institute in Paris, treating a diphtheria toxin with formaldehyde, discovered that the drug had deprived of its toxic properties without violating its specific immunogenic ability. This drug is called

toxoid (toxoid) ... Toxoids are widely used in biology and medicine, and are used today.

The English chemical pathologist John Marrak in 1934, in a book devoted to the critical analysis of the chemistry of antigens and antibodies, substantiated the lattice network theory in their interaction. The theory of network (idiotypic) regulation of immunogenesis by antibodies was subsequently developed and created by the Nobel laureate (in immunology), Danish immunologist Nils Erne. Biochemist Linus Pauling, another Nobel laureate (but chemistry), one of the founders of the theory of the "direct matrix" of antibody formation, in 1940 described the strength of the antigen-antibody interaction and substantiated the stereophysical complementarity of the reaction sites.

Michael Heidelberger (USA) is considered the founder of quantitative immunochemistry. In 1929, Swedish chemist Arne Tiselius and American immunochemist Alvin Kabat, using electrophoresis and ultracentrifugation methods, established that antibodies with a sedimentation constant of 19S are detected in the early period of the immune response, while antibodies with a constant 7S are antibodies of a late response (later designated as antibodies of the IgM and IgG classes respectively). In 1937, A. Tiselius proposed to use the electrophoretic method for separating proteins and determined the activity of antibodies in the globulin fraction of serum. Thanks to these studies, antibodies received the status

immunoglobulins ... In 1935, M. Heidelberger and F. Kendall functionally characterized monovalent or incomplete antibodies as non-precipitating, D. Pressman and Campbell obtained rigorous evidence of the importance of the bivalence of antibodies and their molecular form in binding to the antigen. The works of M. Helderberger, F. Kendall and E. Kabat established that the reactions of specific precipitation, agglutination and fixation of complement are different manifestations of the functions of individual antibodies. Continuing research on the study of antibodies, in 1942 the American immunologist and bacteriologist Albert Koons showed the possibility of labeling antibodies with fluorescent dyes. In 1946, French immunologist Jacques Oudin discovered precipitation bands in a test tube containing antisera and antigen enclosed in agar gel. Two years later, the Swedish bacteriologist Ouchterlonu and independently S.D. Elek modified Oudin's method. The method of double diffusion in the gel developed by them assumed the use of Petri dishes coated with agar gel with wells in the gel, which allowed the antigen and antibodies placed in them to diffuse from the wells into the gel with the formation of precipitation bands.

In subsequent years, the study of antibodies, the development of a methodology for their detection and determination, continued successfully. In 1953, Pierre Grabar, a French immunologist of Russian origin, together with S.A. Williams has developed an immunoelectrophoresis method in which an antigen, such as a serum sample, is electrophoretically separated into its constituents before being reacted with antibodies in a gel to produce precipitation bands. In 1977, the American physicist Rosalyn Yalow was awarded the Nobel Prize for developing a radioimmunological method for the determination of peptide hormones.

Studying the structure of antibodies, the British biochemist Rodney Porter in 1959 treated an IgG molecule with an enzyme (papain). As a result, the antibody molecule was cleaved into 3 fragments, two of which retained the ability to bind antigen, and the third was deprived of this ability, but easily crystallized. In this regard, the first two fragments were named Fab- or antigen-binding fragments (Fragment antigen-binding), and the third - Fe- or crystallizable fragment (Fragment crystallizable). Subsequently, it turned out that regardless of the antigen-binding specificity, antibody molecules of the same isotype of a given individual are strictly identical (invariant). In this regard, the Fc fragments received a second name - constant. Currently, Fc fragments are referred to as both crystallizable (Fe - Fragment crysnallizable) and as constant (Fe - Fragment constant). A significant contribution to the study of the structure of immunoglobulins was made by Henry Kunkel, Xyg Fudenberg, Frank Putman. Alfred Nisonov found that after treating the IgG molecule with another enzyme - pepsin, not three fragments are formed, but only two - fragments F (ab ') 2 and Fe. In 1967 R.C. Valentine and N.M.J. Green received the first electron micrograph of an antibody, and a little later, in 1973, F.W. Putman et al have published the complete amino acid sequence of the IgM heavy chain. In 1969, the American researcher Gerald Edelman published his findings on the primary amino acid sequence of human myeloma protein (IgG) isolated from the patient's serum. For their research, Rodney Porter and Gerald Edelman were awarded the Nobel Prize in 1972.

The most important stage in the development of immunology was the development in 1975 of a biotechnological method for creating hybridomas and obtaining monoclonal antibodies on their basis. The methodology was developed by German immunologist Georg Köhler and Argentine molecular biologist Cesar Milstein. The use of monoclonal antibodies has revolutionized immunology. Without their use, the functioning and further development of neither fundamental nor clinical immunology is unthinkable. The studies of G. Koehler and S. Mil-stein opened the era

Another important factor of humoral immunity is cytokines, like antibodies, which are products of immunocytes. However, in contrast to antibodies characterized predominantly by effector functions and to a lesser extent by regulatory ones, cytokines are predominantly regulatory immunity molecules and, to a much lesser extent, effector ones.

Apparently, the discovery of complement described above, associated with the names of Jules Bordet, Hans Buchner, Paul Ehrlich, and others, was the first description of humoral factors that play, in addition to antibodies, an outstanding role in immunological reactions. Subsequent, most significant discoveries of cytokines - factors of humoral immunity, through which the functions of immunocytes are mediated - transfer factor, tumor necrosis factor, interleukin-1, interferon, a factor inhibiting the migration of macrophages, etc., date back to the 30s of the XX century.

  • History of the development of immunology
  • Summed up the first results of the activities of the information and advisory teams in the current year
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The process of formation and development of the science of immunity was accompanied by the creation of various kinds of theories that laid the foundation for science. Theoretical teachings served as explanations for the complex mechanisms and processes of the human internal environment. The presented publication will help to consider the basic concepts of the immune system, as well as to get acquainted with their founders.

A cough is a non-specific defense reaction of the body. Its main function is to cleanse the respiratory tract from sputum, dust or foreign matter.

For its treatment in Russia, a natural drug "Immunity" was developed, which is successfully used today. It is positioned as a drug to increase immunity, but relieves coughs by 100%. The presented medicine is a composition of a unique synthesis of thick, liquid substances and medicinal herbs, which helps to increase the activity of immune cells without disrupting the biochemical reactions of the body.

The cause of the cough is not important, whether it's seasonal cold, swine flu, pandemic, elephant flu at all - it doesn't matter. An important factor is that it is a respiratory virus. And "Immunity" copes with this the best and absolutely harmless!

What is the theory of immunity?

Immunity theory - is a doctrine, generalized by experimental research, based on the principles and mechanisms of action of immune defense in the human body.

Basic theories of immunity

Theories of immunity were created and developed over a long period of time by I.I. Mechnikov and P. Erlich. The founders of the concepts laid the foundation for the development of the science of immunity - immunology. The basic theoretical teachings will help to consider the principles of the development of science and features.

Basic theories of immunity:

  • The fundamental concept in the development of immunology was theory of the Russian scientist Mechnikov I.I.... In 1883, a representative of the Russian scientific community proposed a concept according to which mobile cellular elements are present in the human internal environment. They are able to swallow with the whole body and digest foreign microorganisms. The cells are called macrophages and neutrophils.
  • The founder of the theory of immunity, which was developed in parallel with the theoretical teaching of Mechnikov, was the concept of the German scientist P. Ehrlich... According to the teachings of P. Ehrlich, it was found that microelements appear in the blood of animals infected with bacteria, destroying foreign particles. Protein substances are called antibodies. A characteristic feature of antibodies is their focus on resistance to a specific microbe.
  • The doctrine of M.F.Burnet. His theory was based on the assumption that immunity is an antibody response aimed at recognizing and separation of your own and dangerous trace elements... Serves as creator clonal breeding theory of immune defense... In accordance with the presented concept, one clone of lymphocytes reacts to one specific trace element. The designated theory of immunity was proved and as a result it was revealed that the immune response acts against any foreign organisms (transplant, tumor).
  • Instructional theory of immunity the date of creation is considered to be 1930. The founders were F. Breinl and F. Gaurovitz. According to the concept of scientists, an antigen is a place for antibodies to join. Antigen is also a key element of the immune response.
  • The theory of immunity was also developed M. Heidelberg and L. Pauling... According to the presented teaching, compounds are formed from antibodies and antigens in the form of a lattice. The creation of the lattice will be possible only if there are three determinants for the antigen molecule in the antibody molecule.
  • Immunity concept on the basis of which the theory of natural selection was developed N. Erne... The founder of the theoretical doctrine suggested that the human body contains molecules complementary to foreign microorganisms that enter the human internal environment. The antigen does not bind or alter existing molecules. It contacts the corresponding antibody in the blood or cell and combines with it.

The presented theories of immunity laid the foundation for immunology and allowed scientists to develop historically formed views regarding the functioning of the human immune system.

Cellular

The founder of the cellular (phagocytic) theory of immunity is the Russian scientist I. Mechnikov. While studying marine invertebrates, the scientist found that some cellular elements absorb foreign particles that penetrate the internal environment. Mechnikov's merit lies in drawing an analogy between the observed process involving invertebrates and the process of absorption of the blood of vertebrates by white cellular elements. As a result, the researcher put forward the opinion according to which the absorption process acts as a protective reaction of the body, accompanied by inflammation. As a result of the experiment, the theory of cellular immunity was put forward.

The cells that carry out protective functions in the body are called phagocytes.

When children fall ill with acute respiratory viral infections or flu, they are treated mainly with antibiotics to lower the temperature or various cough syrups, also in other ways. However, drug treatment often has a very detrimental effect on the child's, not yet strengthened body.

It is possible to cure children from the presented ailments with the help of Immunity drops. It kills viruses in 2 days and eliminates the secondary signs of influenza and ODS. And in 5 days it removes toxins from the body, shortening the rehabilitation period after an illness.

Distinctive features of phagocytes:

  • Implementation of protective functions and removal of toxic substances from the body;
  • Presentation of antigens on the cell membrane;
  • Isolation of a chemical from other biological substances.

The mechanism of action of cellular immunity:

  • In the cellular elements, the process of attachment of phagocyte molecules to bacteria and viral particles takes place. The presented process contributes to the elimination of foreign elements;
  • Endocytosis affects the creation of a phagocytic vacuole - a phagosome. Granules of macrophages and azurophilic and specific granules of neutrophil move to the phagosome, and combine with it, releasing their contents into the phagosome tissue;
  • In the process of absorption, generating mechanisms are enhanced - specific glycolysis and oxidative phosphorylation in macrophages.

Humoral

The founder of the humoral theory of immunity was the German researcher P. Ehrlich. The scientist argued that the destruction of foreign elements from the internal environment of a person is possible only with the help of the protective mechanisms of blood. The findings were presented in a unified theory of humoral immunity.

According to the author, humoral immunity is based on the principle of the destruction of foreign elements through the fluids of the internal environment (through the blood). Substances that carry out the process of eliminating viruses and bacteria are divided into two groups - specific and non-specific.

Non-specific factors of the immune system represent the inherited resistance of the human body to diseases. Non-specific antibodies are universal and affect all groups of dangerous microorganisms.

Specific factors of the immune system (protein elements). They are created by B - lymphocytes, which form antibodies that recognize and destroy foreign particles. A feature of the process is the formation of immune memory, which prevents the invasion of viruses and bacteria in the future.

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The merit of the researcher lies in establishing the fact of inherited antibodies in mother's milk. The result is a passive immune system. Its duration is six months. After the child's immune system begins to function independently and develop its own cellular defense elements.

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One of the complications of flu and colds is otitis media. Doctors often prescribe antibiotics to treat otitis media. However, it is recommended to use the drug "Immunity". This tool was developed and clinically tested at the Research Institute of Medicinal Plants of the Academy of Medical Sciences. The results show that 86% of patients with acute otitis media, taking the drug, got rid of the disease in 1 course of use.

Early 1880s Mechnikovin Messina, Italy, sending his family to watch a circus performance, calmly examined a transparent larva of a starfish under a microscope. He saw how the mobile cells surround a foreign particle that has entered the body of the larva. The absorption phenomenon was also observed before Mechnikov, but it was generally believed that this was simply a preparation for the transport of particles by blood. Suddenly, Mechnikov had an assumption: what if this is not a mechanism of transport, but protection? Mechnikov immediately injected into the larva's body pieces of thorns of a tangerine tree, which he had prepared instead of a New Year tree for his children. Moving cells again surrounded the foreign bodies and consumed them.

If the motile cells of the larva, he thought, were protecting the organism, they must also absorb bacteria. And this assumption was confirmed. Mechnikov had previously observed more than once how white blood cells - leukocytes - also gather around a foreign particle that has entered the body, forming a focus of inflammation. In addition, after many years of work in the field of comparative embryology, he knew that these mobile cells in the body of the larva and human leukocytes originate from the same germ layer - the mesoderm. It turned out that all organisms with blood or its precursor - hemolymph, have a single defense mechanism - the absorption of foreign particles by blood cells. This is how the fundamental mechanism was discovered by which the body protects itself from the penetration of foreign substances and microbes into it. At the suggestion of Professor Klaus from Vienna, to whom Mechnikov told about his discovery, the protective cells were called phagocytes, and the phenomenon itself was called phagocytosis. The mechanism of phagocytosis has been confirmed in humans and higher animals. Human leukocytes are surrounded by microbes that have entered the body and, like amoeba, form protrusions, cover a foreign particle from all sides and digest it.

Paul Ehrlich

Paul Ehrlich (1854-1915) was a prominent representative of the German school of microbiology. Since 1891 Ehrlich was looking for chemical compounds capable of suppressing the life activity of pathogens. Introduced the treatment of four-day malaria with methylene blue dye, treatment of syphilis with arsenic.



Starting with work with diphtheria toxin at the Institute of Infectious Diseases. Ehrlich created the theory of humoral immunity (in his terminology - the theory of side chains). According to her, microbes or toxins contain structural units - antigens, which cause the formation of aptibodies in the body - special proteins of the globulin class. Antibodies have stereospecificity, that is, a conformation that allows them to bind only those antigens in response to the penetration of which they arose. So Ehrlich subordinated the antigen-antibody interaction to the laws of stereochemistry. At first, antibodies exist in the form of special chemical groups (side chains) on the cell surface (fixed receptors), then some of them are separated from the cell surface and begin to circulate with the blood (freely transcribed receptors). When they meet microbes or toxins, antibodies bind to them, immobilize them and prevent their effect on the body. Ehrlich showed that the toxic effect of a toxin and its ability to bind to an antitoxin are different functions and can be acted upon separately. It was possible to increase the concentration of antibodies by repeated injections of the antigen - this is how Ehrlich solved the problem of obtaining highly effective sera that worried Bering. Ehrlich introduced the distinction between passive immunity (the introduction of ready-made antibodies) and active immunity (the introduction of antigens to stimulate their own antibody production). Investigating the plant poison ricin, Ehrlich showed that antibodies do not appear immediately after the antigen is injected into the blood. He was the first to study the transfer of some of the immune properties from the mother to the fetus through the placenta and to the baby with milk.

A long and persistent discussion arose between Mechnikov and Ehrlich in the press about the "true theory of immunity." As a result, phagocytosis is called cellular, and antibody formation - humoral immunity. Mechnikov and Ehrlich shared the 1908 Nobel Prize.

Beringengaged in the creation of sera by selecting bacterial cultures and toxins that he injected into animals. One of his greatest achievements is the creation in 1890 of anti-tetanus serum, which proved to be very effective in the prevention of tetanus in injuries, although ineffective in a later period, with an already developed disease.

“Bering wanted the honor of discovering the anti-diphtheria serum to belong to German, not French, scientists. In search of vaccinations for animals infected with diphtheria, Bering made sera from various substances, but the animals died. Once he used iodine trichloride for vaccination. True, this time the guinea pigs fell seriously ill, but none of them died. Encouraged by the first success, Bering, after waiting for the experimental pigs to recover, vaccinated them from a broth with a diphtheria toxin that had been strained by the Roux method, in which diphtheria bacilli had been grown earlier. The animals survived the vaccination admirably, despite receiving a huge dose of the toxin. This means that they have acquired immunity against diphtheria, they are not afraid of either bacteria or the poison they release. Bering decided to improve his method. He mixed the blood of the recovered guinea pigs with filtered liquid containing diphtheria toxin and injected the mixture into healthy guinea pigs - none of them got sick. So, Bering decided, the blood serum of animals that have acquired immunity contains an antidote for the diphtheria poison, some kind of "antitoxin".

By inoculating the serum obtained from recovered animals healthy, Bering made sure that guinea pigs receive immunity not only when infected with bacteria, but also when exposed to a toxin. Later he was convinced that this serum also has a therapeutic effect, that is, if sick animals are vaccinated, they recover. At the clinic for childhood diseases in Berlin, on December 26, 1891, a child who was dying of diphtheria was vaccinated from the serum of a mumps that had recovered, and the child recovered. Emil Bering and his boss, Robert Koch, triumphed over the formidable disease. Now Emile Roux has taken up the matter again. By inoculating horses with diphtheria toxin at short intervals, he gradually achieved complete immunization of the animals. Then he took several liters of blood from horses, isolated serum from it, from which he began to inoculate sick children. Already the first results exceeded all expectations: the mortality rate, which had previously reached 60 to 70% in diphtheria, dropped to 1–2%.

In 1901, Bering received the Nobel Prize in Physiology or Medicine for his work on serum therapy.