Corresponding Member of the Russian Academy of Sciences Sergei Nedospasov, Boris Rudenko, columnist for the journal Science and Life.

Revolutionary breakthroughs in any field of science occur infrequently, once or twice a century. And in order to realize that a revolution in the knowledge of the surrounding world has really taken place, to evaluate its results, the scientific community and society as a whole sometimes need more than one year or even more than one decade. In immunology, such a revolution occurred at the end of the last century. It was prepared by dozens of prominent scientists who put forward hypotheses, made discoveries and formulated theories, and some of these theories and discoveries were made a hundred years ago.

Paul Ehrlich (1854-1915).

Ilya Mechnikov (1845-1916).

Charles Janeway (1943-2003).

Jules Hoffmann.

Ruslan Medzhitov.

Drosophila, a mutant in the Toll gene, became overgrown with fungi and died because it does not have immune receptors that recognize fungal infections.

Two schools, two theories

Throughout the 20th century, until the early 1990s, in research on immunity, scientists proceeded from the belief that higher vertebrates, and in particular humans, have the most advanced immune system. This is what should be studied first. And if something has not yet been “under-discovered” in the immunology of birds, fish and insects, then this, most likely, does not play a special role in advancing on the path of understanding the mechanisms of protection against human diseases.

Immunology as a science arose a century and a half ago. Although the first vaccination is associated with the name of Jenner, the founding father of immunology is rightfully considered the great Louis Pasteur, who began to look for a clue to the survival of the human race, despite the regular devastating epidemics of plague, smallpox, cholera that fall on countries and continents like a punishing sword of fate. Millions, tens of millions of deaths. But in cities and towns, where funeral teams did not have time to remove corpses from the streets, there were those who, on their own, without the help of healers and sorcerers, coped with a deadly attack. And also those who were not affected by the disease at all. This means that there is a mechanism in the human body that protects it from at least some intrusions from the outside. It's called immunity.

Pasteur developed ideas about artificial immunity, developing methods for creating it through vaccination, but it gradually became clear that immunity exists in two forms: natural (innate) and adaptive (acquired). Which of them is more important? Which one plays a role in successful vaccination? At the beginning of the 20th century, in response to this fundamental question, two theories, two schools, of Paul Erlich and Ilya Mechnikov, collided in a sharp scientific debate.

Paul Erlich has never been to Kharkov or Odessa. He passed his universities in Breslau (Breslau, now Wroclaw) and Strasbourg, worked in Berlin, at the Koch Institute, where he created the world's first serological control station, and then headed the Institute for Experimental Therapy in Frankfurt am Main, which bears his name today. And here it should be recognized that, conceptually, Ehrlich has done more for immunology in the entire history of the existence of this science than anyone else.

Mechnikov discovered the phenomenon of phagocytosis - the capture and destruction by special cells - macrophages and neutrophils - of microbes and other biological particles alien to the body. It was this mechanism, he believed, that is the main one in the immune system, building lines of defense against invading pathogens. It is phagocytes that rush into the attack, causing an inflammation reaction, for example, with an injection, a splinter, etc.

Erlich argued the opposite. 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 an aggressor. Ehrlich's theory was called the theory of humoral immunity.

It is interesting that irreconcilable scientific rivals - Mechnikov and Erlich - shared in 1908 the Nobel Prize in Physiology or Medicine for their work in the field of immunology, although by this time the theoretical and practical successes of Erlich and his followers, it would seem, completely refuted the views of Mechnikov. It was even said that the prize was awarded to the latter, rather, on the basis of the totality of his merits (which is not at all excluded and not shameful: immunology is only one of the areas in which the Russian scientist worked, his contribution to world science is enormous). However, even if so, the members of the Nobel Committee, as it turned out, were much more right than they themselves believed, although confirmation of this did not come until a century later.

Erlich died in 1915, Mechnikov outlived his opponent by only a year, so that the most fundamental scientific dispute developed without the participation of his initiators until the end of the century. In the meantime, everything that happened in immunology over the next decades confirmed the correctness of Paul Ehrlich. It was found that white blood cells, lymphocytes, are divided into two types: B and T (here it must be emphasized that the discovery of T-lymphocytes in the middle of the twentieth century transferred the science of acquired immunity to a completely different level - the founders could not foresee this). It is they who organize protection from viruses, microbes, fungi and, in general, from substances hostile to the body. B-lymphocytes produce antibodies that bind foreign protein, neutralizing its activity. And T-lymphocytes destroy infected cells and contribute to the removal of the pathogen from the body in other ways, and in both cases a “memory” of the pathogen is formed, so that it is already much easier for the body to fight a repeated infection. These protective lines are able to deal with their own, but reborn protein, which becomes dangerous for the body, in the same way. Unfortunately, in the event of a failure in setting up the most complex mechanism of adaptive immunity, such an ability can cause autoimmune diseases, when lymphocytes, having lost the ability to distinguish their proteins from others, begin to “shoot at their own” ...

Thus, until the 1980s, immunology mainly developed along the path indicated by Erlich, and not by Mechnikov. Incredibly complex, fantastically refined by millions of years of evolution, adaptive immunity gradually revealed its mysteries. Scientists created vaccines and serums that were supposed to help the body organize an immune response to infection as quickly and efficiently as possible, and received antibiotics that could suppress the biological activity of the aggressor, thereby facilitating the work of lymphocytes. True, since many microorganisms are in symbiosis with the host, antibiotics attack their allies with no less enthusiasm, weakening and even nullifying their beneficial functions, but medicine noticed this and sounded the alarm much, much later ...

However, the milestones of a complete victory over diseases, which at first seemed so achievable, moved further and further towards the horizon, because over time, questions appeared and accumulated that the prevailing theory found it difficult to answer or could not answer at all. And the creation of vaccines did not go as smoothly as expected.

It is known that 98% of creatures living on Earth are generally deprived of adaptive immunity (in evolution it appears only from the level of jawed fish). But they all also have their own enemies in the biological microcosm, their own diseases and even epidemics, which, however, the populations cope with quite successfully. It is also known that in the human microflora there are a lot of organisms that, it would seem, are simply obliged to cause diseases and initiate an immune response. However, this does not happen.

There are dozens of similar questions. For decades they remained open.

How revolutions start

In 1989, the American immunologist Professor Charles Janeway published a work that was soon recognized as visionary, although, like the theory of Mechnikov, it had and still has serious, erudite opponents. Janway suggested that human cells responsible for immunity have special receptors that recognize some structural components of pathogens (bacteria, viruses, fungi) and trigger a response mechanism. Since there are an innumerable number of potential pathogens in the sublunar world, Janway suggested that the receptors would also recognize some kind of "invariant" chemical structures characteristic of a whole class of pathogens. Otherwise, just not enough genes!

A few years later, Professor Jules Hoffmann (who later became president of the French Academy of Sciences) discovered that the fruit fly - almost an indispensable participant in the most important discoveries in genetics - has a defense system, until then misunderstood and unappreciated. It turned out that this fruit fly has a special gene that is not only important for the development of the larva, but is also associated with innate immunity. If this gene is spoiled in the fly, then when it is infected with fungi, it dies. Moreover, it will not die from other diseases, for example, a bacterial one, but inevitably from a fungal one. The discovery led to three important conclusions. First, the primitive fruit fly is endowed with powerful and effective innate immunity. Secondly, its cells have receptors that recognize infections. Thirdly, the receptor is specific to a certain class of infections, that is, it is able to recognize not any foreign “structure”, but only a well-defined one. And this receptor does not protect against another “structure”.

These two events - an almost speculative theory and the first unexpected experimental result - should be considered the beginning of the great immunological revolution. Further, as happens in science, events developed incrementally. Ruslan Medzhitov, who graduated from Tashkent University, then postgraduate studies at Moscow State University, and later became a professor at Yale University (USA) and a rising star in the world of immunology, was the first to discover these receptors on human cells.

So, after almost a hundred years, the long-standing theoretical dispute between great scientific rivals was finally resolved. I decided that both were right - their theories complemented each other, and the theory of I. I. Mechnikov received new experimental confirmation.

And in fact there was a conceptual revolution. It turned out that for all beings on Earth, innate immunity is the main one. And only in the most "advanced" on the ladder of evolution of organisms - higher vertebrates, in addition, acquired immunity appears. However, it is the innate that directs its launch and subsequent operation, although many of the details of how it all regulates remain to be established.

"His Excellency's Adjuvant"

New views on the interaction of the innate and acquired branches of immunity helped to understand what was not clear until now.

How do vaccines work when they work? In a general (and very simplified) form, it goes something like this. A weakened pathogen (usually a virus or bacterium) is injected into the blood of a donor animal such as a horse, cow, rabbit, etc. The immune system of the animal produces a protective response. If the protective response is associated with humoral factors - antibodies, then its material carriers can be purified and transferred into human blood, while simultaneously transferring the protective mechanism. In other cases, a weakened (or killed) pathogen is infected or immunized with the person himself, hoping to trigger an immune response that can protect against the real pathogen and even gain a foothold in cellular memory for many years. This is how Edward Jenner at the end of the 18th century, for the first time in the history of medicine, vaccinated against smallpox.

However, this technique does not always work. It is no coincidence that there are still no vaccines against AIDS, tuberculosis and malaria - the three most dangerous diseases on a global scale. Moreover, for many simple chemical compounds or proteins that are foreign to the body and would simply have to initiate an immune system response, the answer does not arise! And often this happens for the reason that the mechanism of the main defender - innate immunity - remains unawakened.

One way to overcome this obstacle was experimentally demonstrated by the American pathologist J. Freund. The immune system will work at full strength if the hostile antigen is mixed with an adjuvant. An adjuvant is a kind of intermediary, an assistant in immunization; in Freund's experiments, it consisted of two components. The first - water-oil suspension - performed a purely mechanical task of slow release of the antigen. And the second component, at first glance, is rather paradoxical: dried and well-crushed tuberculosis bacteria (Koch's sticks). The bacteria are dead, they are not capable of causing infection, but the innate immune receptors will still immediately recognize them and turn on the defense mechanisms at full capacity. That's when the process of activation of the adaptive immune response to the antigen that was mixed with the adjuvant starts.

Freund's discovery was purely experimental and therefore may seem private. But Janway caught a moment of general significance in him. Moreover, he even called the inability to induce a full-fledged immune response to a foreign protein in experimental animals or in humans a “dirty little secret of immunologists” (hinting that this can only be done in the presence of an adjuvant, and no one understands how the adjuvant works).

Janway and suggested that the innate immune system recognizes bacteria (both live and killed) by the components of the cell walls. Bacteria that live “on their own” need strong multi-layered cell walls for external protection. Our cells, under a powerful sheath of external protective tissues, do not need such sheaths. And bacterial shells are synthesized with the help of enzymes that we don’t have, and therefore the components of bacterial walls are just those chemical structures, ideal signaling agents of the threat of infection, for which the body has made receptors-identifiers in the process of evolution.

A small digression in the context of the main topic.

There was a Danish bacteriologist Christian Joachim Gram (1853-1938), who systematized bacterial infections. He found a substance that stained bacteria of one class, but not another. Those that turned pink are now called Gram-positive after the scientist, and those that remained colorless are Gram-negative. There are millions of different bacteria in each class. For humans - harmful, neutral and even beneficial, they live in soil, water, saliva, intestines - anywhere. Our defense receptors are able to selectively recognize both, including the appropriate defense against those that are dangerous to their carrier. And the Gram dye could distinguish them by binding (or not binding) to the same "invariant" components of the bacterial walls.

It turned out that the walls of mycobacteria - namely, tubercle bacilli belong to them - are especially complex and are recognized by several receptors at once. This is probably why they have excellent adjuvant properties. So, the point of using an adjuvant is to deceive the immune system, send it a false signal that the body is infected with a dangerous pathogen. Force to react. But in fact, there is no such pathogen in the vaccine at all, or it is not so dangerous.

There is no doubt that other, including non-natural, adjuvants for immunizations and vaccinations will be found. This new direction of biological science is of tremendous importance for medicine.

Turn on / off the desired gene

Modern technologies make it possible to turn off (“knock out”) a single gene in an experimental mouse that encodes one of the innate immunity receptors. For example, responsible for the recognition of the same gram-negative bacteria. Then the mouse loses the ability to provide its protection and, being infected, dies, although all other components of its immunity are not violated. This is how the work of immunity systems at the molecular level is being experimentally studied today (we have already discussed the example of a fruit fly). In parallel, clinicians are learning to link people's lack of immunity to certain infectious diseases to mutations in specific genes. For hundreds of years, examples have been known when in some families, clans, and even tribes, the mortality rate of children at an early age from very specific diseases was extremely high. Now it becomes clear that in some cases the cause is a mutation of some component of innate immunity. The gene is turned off - partially or completely. Since most of our genes are in two copies, special efforts must be made to ensure that both copies are damaged. This can be “achieved” as a result of closely related marriages or incest. Although it would be a mistake to think that this explains all cases of hereditary diseases of the immune system.

In any case, if the cause is known, there is a chance to find a way to avoid the irreparable, at least in the future. If a child with a diagnosed congenital immunity defect is purposefully protected from a dangerous infection until the age of 2-3 years, then with the completion of the formation of the immune system, the mortal danger for him may pass. Even without one level of protection, he will be able to handle the threat and possibly live a full life. The danger will remain, but its level will decrease significantly. There is still hope that someday gene therapy will enter everyday practice. Then the patient will simply have to transfer the “healthy” gene, without mutation. In mice, scientists can not only turn off the gene, but also turn it on. In humans it is much more difficult.

About the benefits of curdled milk

It is worth recalling one more foresight of I. I. Mechnikov. A hundred years ago, he associated the activity of phagocytes discovered by him with human nutrition. It is well known that in the last years of his life he actively consumed and promoted yogurt and other fermented milk products, arguing that maintaining the necessary bacterial environment in the stomach and intestines is extremely important for both immunity and life expectancy. And then he was right again.

Indeed, research in recent years has shown that the symbiosis of intestinal bacteria and the human body is much deeper and more complex than previously thought. Bacteria not only help the process of digestion. Since they contain all the characteristic chemical structures of microbes, even the most beneficial bacteria must be recognized by the innate immune system on intestinal cells. It turned out that through the receptors of innate immunity, bacteria send some “tonic” signals to the body, the meaning of which has not yet been fully established. But it is already known that the level of these signals is very important, and if it is reduced (for example, there are not enough bacteria in the intestine, in particular from the abuse of antibiotics), then this is one of the factors in the possible development of oncological diseases of the intestinal tract.

Twenty years that have passed since the last (last?) revolution in immunology is too short a period for the wide practical application of new ideas and theories. Although it is unlikely that there is at least one serious pharmaceutical company left in the world that is developing without taking into account new knowledge about the mechanisms of innate immunity. And some practical progress has already been made, in particular in the development of new adjuvants for vaccines.

And a deeper understanding of the molecular mechanisms of immunity - both innate and acquired (we must not forget that they must act together - friendship won) - will inevitably lead to significant progress in medicine. Doubt it is not worth it. You just have to wait a little.

But where the delay is highly undesirable is in educating the population, as well as in changing stereotypes in the teaching of immunology. Otherwise, our pharmacies will continue to burst with home-grown drugs that supposedly enhance immunity universally.

Sergei Arturovich Nedospasov - Head of the Department of Immunology, Faculty of Biology, Lomonosov Moscow State University M. V. Lomonosov, head of the laboratory of the Institute of Molecular Biology. V. A. Engelgardt Institute of Physical and Chemical Biology, Russian Academy of Sciences, Head of Department A. N. Belozersky.

"Science and Life" about immunity:

Petrov R. Right on target. - 1990, No. 8.

Mate J. Man from the point of view of an immunologist. - 1990, No. 8.

Tchaikovsky Yu. Anniversary of Lamarck-Darwin and revolution in immunology. - 2009, No. , .

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

I. I. Mechnikov was born in 1845 in the Kharkov province and graduated from Kharkov University. However, Mechnikov carried out the most significant scientific research 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 special mobile cells in it that absorbed and digested food particles.

• Immunity. Types of immunity;
• Types of immunity;
• Immunization;
• Mechanisms of protection of cellular homeostasis of the body.

Mechnikov suggested that they also "serve in the body to counteract harmful agents". The scientist called these cells phagocytes. Phagocyte cells were also 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 member 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 Erlich(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 produced by a bacterium, 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 of the body to start producing antibodies, the antigen has to recognize receptors on the cell surface. Ehrlich's ideas found their experimental confirmation a decade later.

Paul Erlich

Mechnikov and Erlich created various theories, but neither of them sought to defend only his own point of view. They saw that both theories were correct. It has now been proven that both immune mechanisms, both Mechnikov's phagocytes and Ehrlich's antibodies, do work simultaneously in the body.

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

Red blood cells containing hemoglobin 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 type of immunity, cellular and humoral links are distinguished.

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

Tags: Ilya Ilyich MechnikovImmunityPaul Ehrlich

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

Created the cellular theory of immunity

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

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Hey! Here is a selection of topics with answers to your question: Which of the scientists is considered the creator of the cellular theory of immunity?

Answer from LANA Russian evolutionary biologist Ilya Mechnikov was at the origin of the knowledge of cellular immunity. In 1883, he made the first report on the phagocytic (cellular) theory of immunity at a congress of physicians and natural scientists in Odessa. Mechnikov then argued that the ability of the mobile cells of invertebrates to absorb food particles, i.e., to participate in digestion, is in fact their ability to absorb in general everything “alien” that is not characteristic of the body: various microbes, inert particles, dying parts of the body. Humans also have amoeboid motile cells - macrophages and neutrophils. But they "eat" food of a special kind - pathogenic microbes. Evolution has preserved the absorptive 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 developed his theory of immune defense against infection. He was aware of the fact that in the blood serum of animals infected with bacteria, protein substances appear that can kill pathogenic microorganisms. These substances were subsequently named by him "antibodies". The most characteristic property of antibodies is their pronounced specificity. Formed as a protective agent against one microorganism, they neutralize and destroy only it, remaining indifferent to others. In an attempt to understand this phenomenon of specificity, Ehrlich put forward the theory of "side chains", according to which antibodies in the form of receptors preexist on the surface of cells. In this case, the antigen of microorganisms acts as a selective factor. Having come into contact with a specific receptor, it ensures enhanced production and circulation of only that particular receptor (antibody). Ehrlich's foresight is astounding, since with some modifications this generally speculative theory has now been confirmed. Two theories - cellular (phagocytic) and humoral - in the period of their emergence stood on antagonistic positions. The schools of Mechnikov and Erlich fought for scientific truth, not suspecting that each blow and each parry brought their 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 "one's own" from everything "foreign", he raised the question of the significance 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 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. B. 9). The formula of such a theory is simple: one clone of lymphocytes is able to respond only to one specific antigenic specific determinant.

Answer from Portvein777tm no the question is incorrect, this is the same as asking what is the calorific value of the cellular or humoral, there is no theta and it was not Bullshit, therefore - due to improper treatment, individuals so often die read our book link

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Hey! Here are some other threads with relevant answers:

Answer the question:

The development of the science of immunity | Meddoc

Immunology is the science of the body's defense reactions 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, back in the Middle Ages, it was noticed that a person who had an infectious disease becomes immune to it: that is why people who recovered from plague and cholera were attracted to care for the sick and to bury the dead. Doctors 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

Creating Vaccines

The pioneer in this field can be considered the Englishman Edward Jenner (1749-1823), who managed to rid mankind of smallpox. Observing cows, he noticed that the animals were susceptible to infection, the symptoms of which were similar to smallpox (later this disease of cattle was called "cowpox"), and bubbles formed on their udders, strongly reminiscent of smallpox. During milking, the liquid contained in these vesicles was often rubbed into the skin of people, but milkmaids rarely got smallpox. Jenner could not give a scientific explanation for this fact, because at that time it was not yet known about the existence of pathogenic microbes. As it turned out later, the smallest microscopic creatures - viruses that cause smallpox of cows, are somewhat different from those viruses that infect humans. However, the human immune system also reacts to them.

In 1796, Jenner inoculated a liquid taken from cow pockmarks into a healthy eight-year-old boy. He had a slight malaise, which soon passed. A month and a half later, the doctor inoculated him with human 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 the work of Jenner, he expressed the idea that if a person is infected with weakened microbes that cause a mild illness, then in the future the person will not get sick with this disease. He has immunity, and his leukocytes and antibodies can easily cope with pathogens. Thus, the role of microorganisms in infectious diseases has been proven.

Pasteur developed a scientific theory that made it possible to use 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. This damages the cells of the nervous system. The patient develops rabies - it is impossible to drink, because the water causes convulsions of the pharynx and larynx. Due to paralysis of the respiratory muscles or cessation of cardiac activity, death can occur. Therefore, when bitten by a dog or other animal, it is urgent to vaccinate against rabies. Serum, created by a French scientist in 1885, has been successfully used to this day.

Immunity against rabies occurs only for 1 year, so if you are bitten again after this period, you should be vaccinated 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 lies in the fact that foreign bodies are destroyed by special cells - phagocytes.

Ilya Ilyich Mechnikov

In 1890, the German bacteriologist Emil von Behring (1854-1917) found that in response to the introduction of microbes and their poisons, protective substances are produced in the body - 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 their 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 individuality of antigens became especially acute with the advent and development of transplantology. In 1945, the English scientist Peter Medawar (1915-1987) proved that the main mechanism of rejection of transplanted organs is immune: the immune system perceives them as foreign and throws antibodies and lymphocytes to fight them. And only in 1953, when the phenomenon opposite to immunity was discovered - immunological tolerance (loss or weakening of the body's ability to immune response to a given antigen), transplant operations became much more successful.

Articles: The history of the fight against smallpox. Vaccination | Immunological centers in Kyiv

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

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

Who discovered the mechanisms of immunity?

Ilya Ilyich Mechnikov and Paul Erlich. They also created the first theories of immunity. Theories are very different. 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 still Pasteur.

Pasteur discovered a new principle, he discovered a phenomenon whose mechanisms 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 transcript came later. Now penicillin is synthesized in chemical plants. But the father is Fleming. Konstantin Eduardovich Tsiolkovsky is the father of rocket science. 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 science, did not overshadow the significance of his work.

“From the most ancient to the latest times, it was taken for granted that the body has some kind of ability to react against harmful influences entering it from outside. This resistance ability has been called variously. Mechnikov's research quite firmly establishes the fact that this ability depends on the property of phagocytes, mainly white blood cells and connective tissue cells, to devour microscopic organisms that enter the body of a higher animal. So the Russian Medicine magazine told about the report of Ilya Ilyich Mechnikov in the Society of Kyiv Doctors, made on January 21, 1884.

Of course not. The report formulated thoughts that were born in the head of the scientist much earlier, during work. Separate elements of the theory had already been published in articles and reports by that time. 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 Behring, Richard Pfeiffer, Robert Koch, Rudolf Emmerich. They were led in this struggle by Paul Ehrlich, the author of a fundamentally different theory of immunity.

The theories of Mechnikov and Ehrlich excluded one another. The dispute was not fought behind closed doors, but in front of the whole world. At conferences and congresses, on the pages of magazines and books, weapons were crossed everywhere by the next experimental attacks and counterattacks of opponents. The weapons were facts. Only 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 transparent starfish larvae. He recalled that it was on this evening, when the whole family went to the circus, and he stayed to work, that a thought struck him. The idea that these motile cells must be related to the defense of the organism. (Perhaps this should be considered the “moment of birth”.)

Dozens of experiments followed. Foreign particles - splinter, paint grains, bacteria - are captured by mobile cells. Under a microscope, you can see how cells gather around uninvited aliens. Part of the cell is elongated 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 being devoured by it. Mechnikov called these cells phagocytes, which means cells-devourers.

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, of course, is the phagocytosis of bacteria.

Here, a scientist introduces anthrax pathogens into frog tissues. Phagocytes flock to the site of microbial injection. Each captures one, two, or even a dozen bacilli. Cells devour these sticks and digest them.

So here it is, the mysterious mechanism of immunity! This is how the fight against pathogens of contagious diseases is going on. Now it is clear why one person falls ill during a cholera epidemic (and not only cholera!), while the other does not. So, 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 not destroyed by cells at all, but by special substances found in the blood and other body fluids. The concept was called humoral, that is, liquid.

And the argument began...

1887 International Hygiene Congress in Vienna. Mechnikov's phagocytes and his theory are only spoken of in passing, as something completely implausible. Rudolf Emmerich, a Munich bacteriologist and student of the hygienist Max Pettenkofer, reports in his report that he injected the germ of rubella into immune, that is, previously vaccinated, pigs, 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 up" to the microbes.

What does Mechnikov do?

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

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

1891 Another international hygienic congress. Now he has gathered in London. Emil Behring, also a German bacteriologist, enters the discussion. The name of Bering will forever remain in the memory of people. It is associated with a discovery that has saved millions of lives. Bering - the creator of anti-diphtheria serum.

A follower of the humoral theory of immunity, Behring made a very logical assumption. If an animal has suffered some contagious disease in the past and has developed immunity, then the blood serum, its cell-free part, should increase its bactericidal power. If this is the case, then it is possible to artificially introduce microbes to animals, weakened or in small quantities.

It is possible to artificially develop such immunity. And the serum of this animal should kill the corresponding microbes. Bering created anti-tetanus serum. To get it, he introduced the poison of tetanus bacilli to rabbits, 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 an immunized rabbit.

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

But what about the cells-devourers? They injected serum, the part of the blood where there are no cells. And the serum helped fight germs. No cells, no phagocytes entered the body, and yet he received some kind of weapon against microbes. Therefore, the cells have nothing to do with it. There is something in the cell-free part of the blood. So the humoral theory is correct. The phagocytic theory is wrong.

As a result of such a blow, the scientist receives an impetus to new work, to new research. The search begins ... or rather, the search continues, and, naturally, Mechnikov again responds with experiments. As a result, it turns out: it is not the serum that kills the pathogens of diphtheria and tetanus. It neutralizes the toxins and poisons they secrete, and stimulates phagocytes. Serum-activated phagocytes easily deal with disarmed bacteria, whose poisonous secretions are neutralized by antitoxins in the same serum, that is, antivenoms.

The two theories are beginning to converge. Mechnikov still convincingly proves that the main role in the fight against microbes is assigned to the phagocyte. After all, in the end, anyway, the phagocyte takes a 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, one has to agree that the contact of the organism with microbial bodies leads to the accumulation of antibodies circulating in the blood. (A new concept has appeared - an antibody; more about antibodies will be later.) Some microbes, such as cholera vibrios, die and dissolve under the influence of antibodies.

Does this invalidate 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 the main job of capturing and destroying bacteria.

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

The strength of the dispute, the passion and intensity of the controversy remained the same. Ten years later, on the anniversary of Ilya Ilyich Mechnikov, Emil Roux recalled those days:

“Until now, I still see you at the Budapest Congress of 1894 objecting to your opponents: your face is burning, your eyes are sparkling, your hair is tangled. You looked like a demon of science, but your words, your irrefutable arguments, caused applause from the audience. New facts, which at first seemed to contradict the phagocytic theory, soon came into harmonious combination with it.

Such was the dispute. Who won it? All! Mechnikov's theory became coherent and comprehensive. The humoral theory has found its main acting factors - antibodies. Paul Ehrlich, having combined and analyzed the data of the humoral theory, created in 1901 the theory of antibody formation.

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

1908 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 of the war went forward in one direction. This war is good!

Mechnikov and Erlich created the theory of immunity. They argued and won. Everyone was right, even those who seemed wrong. Science won. Humanity won. Everyone wins in a scientific dispute!

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Theory of Immunity - Chemist's Handbook 21

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

The model theory of immunity is presented in 17.10.

The work of I. I. Mechnikov (1845-1916) contributed to the development of scientific microbiology in Russia. 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.

BURNET F. Integrity of the body (a new theory of immunity). Cambridge, 1962, translated from English, 9th ed. l., price 63 kopecks.

The second fundamental theory, brilliantly confirmed by practice, was the phagocytic theory of immunity by I. I. Mechnikov, developed in 1882-1890. The essence of the doctrine of phagocytosis and phagocytes has been described earlier. Here it is only appropriate to emphasize that it was the foundation for the study of cellular immunity and, in essence, created the prerequisites for the formation of an idea of ​​the cellular-humoral mechanisms of immunity.

Back in 1882, I. I. 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, such as cancer cells or cells affected by viruses. But until recently, it was not known exactly how lymphocytes do this. This has come to light recently.

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 well-known 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 specificities on cells, but it took many years before the existence of receptors was experimentally proven and their detailed study began.

Analyzing various theories of immunity, the authors show the leading role of oxidative processes in the defense reactions of plants. The book shows that shifts in the work of the enzymatic apparatus of the cell are the result of the action 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 been of concern to researchers. From 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 up to the present, 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 occurring 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 the antigen, the possibility of distinguishing oneself from someone else, i.e., the absence of a reaction to host tissues, and autoimmune diseases, when such a reaction nevertheless occurs, immunological reactivity in cancer and insufficient immunity when the cancer manages to slip out of the control of the body.

The creator of the cellular theory of immunity is II Mechnikov, who in 1884 published a work on the properties of phagocytes and the role of these cells in the resistance of organisms to bacterial infections. Almost simultaneously, the so-called humoral theory of immunity arose, independently developed by a group of European scientists. Proponents of this theory explained 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 enter the body again. In 1901, P. Ehrlich, having analyzed and generalized the data accumulated by the humoral direction, created a theory of the formation of antibodies. Many years of fierce controversy between I. I. Mechnikov and a group of leading microbiologists of that time led to a comprehensive verification of both theories and their complete confirmation. In 1908, the Nobel Prize in Medicine is awarded to I. I. Mechnikov and P. Erlich 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 their ability to be the causative agent of the disease, i.e., 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, i.e., the body's immunity to infectious diseases.

Discovery of mobile genetic elements Development of clonal selection theory of immunity Development of methods for obtaining myocloial antibodies using hybridomas Discovery 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, as well as van't Hoff in Amsterdam, praised it highly. O tvaJILD visited Arrhenius and offered him a position at his university. This support and the received experimental confirmation of the Arrhenius theory changed the attitude towards him at home. Arrhenius was invited to lecture on physical chemistry at Uppsala University. Loyal to his country, he also rejected offers from Gressen and Berlin and eventually became president of the Physico-Chemical Institute of the Nobel Committee. Arrhenius launched a large research program in the field of physical chemistry. His interests covered issues as far apart as ball lightning, the effect of atmospheric CO2 on glaciers, space physics, and the theory of immunity to various diseases.

P. Ehrlich - a German chemist - put forward a humoral (from 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 been a subject of great debate for many years. It was clear that the organism was preterminated to antigens encountered in the course of phylogenesis, but there were doubts whether there really are T-lymphocytes with receptors for new (synthetic and chemical) antigens, the emergence of which in nature is associated with the development of technical progress in the 20th century. However, special studies carried out using the most sensitive serological methods have revealed in humans and more than 10 species of mammals normal antibodies to a number of chemical haptens - dinitrophenyl, 3-iodine-4-hydroxyphenylacetic acid, etc. Apparently, the three-dimensional structures of receptors are indeed very diverse, and in the body there can always be several cells whose receptors are close enough to a new determinant. It is possible that the final adjustment of the receptor to the determinant can occur after their connection in the process of differentiation of Tr lymphocytes into Tr lymphocytes, after meeting with its antigen, the Tr cell, by one or two divisions, turns into an antigen-recognizing and activated (committed, primed according to the terminology of different authors ) antigen long-lived Tg-cell. Tg-lymphocytes are capable of recycling, can re-enter the thymus, are sensitive to the action of anti-0-, anti-thymocyte and anti-lymphocyte sera. These lymphocytes form the central link of the immune system. After the formation of a clone, i.e., reproduction by dividing 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 (the 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, reduces, in our opinion, the heuristic value of these models. Much more interesting to us is the attempt by 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 advances in infectious immunology, experimental and theoretical immunology remained in its infancy by the middle of the century. Two theories of immunity - cellular and humoral - only lifted the curtain on the unknown. The subtle mechanisms of immune reactivity, the biological range of the action of immunity, remained clear 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 one's own from everything else, he raised the question of the significance of immune mechanisms in maintaining the genetic integrity of the organism during the period of individual (ontogenetic) development. It was Wernet who drew attention to the lymphocyte as the main participant in a specific immune response, giving it the name immunocyte. It was Vernet who predicted, and the Englishman Peter Medawar 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. Wernet remained in the history of immunology as the creator of the clonal selection theory of immunity. The formula of such a theory is simple: one clone of lymphocytes is able to respond only to one specific, antigenic, specific determinant.

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

Ehrlich suggested that binding an antigen to 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 a single cell is capable of producing antibodies that bind more than one type of antigen, he nonetheless anticipated both the clonal selection theory of immunity and the fundamental idea of ​​the existence of receptors for an antigen even before the immune system contacts it. systems.

During the immunological period in the development of microbiology, a number of theories of immunity were created: the humoral theory of P. Ehrlich, the phagocytic theory of I. I. Mechnikov, the theory of idiotypic interactions of N. Erne, the pituitary-hypothalamic-adrenal

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 substances-agents) 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 turn into plasma cells, and several diverse subpopulations arise from undifferentiated T-cells. In 1966, T-lymphocyte cytokines were discovered, which determine the cooperation (mutual action) of immunocompetent cells. Thus, Mechnikov-Erlich's cell-humoral theory of 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 in the development of immunology were very eventful. 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 pigeons with heated bacilli, the causative agents of swine cholera, caused a state of immunity to a 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, American bacteriologist George Nettall first described the antibacterial properties of blood and other bodily fluids. The German bacteriologist Hans Buchner continued these studies and named alexin the heat-sensitive bactericidal factor of cell-free serum, later called complement by Ehrlich and Morgenroth. Employees of the Pasteur Institute (France) Emile Py and Alexandre Yersin found that the cell-free culture filtrate of diphtheria bacillus contains an exotoxin that can induce the disease. In December 1890, Karl Frenkel published his observations showing the induction of immunity by heat-killed bouillon culture of diphtheria bacillus. In December of the same year, the works of the German bacteriologist Emil von Behring and the Japanese bacteriologist and researcher Shibasaburo Kitasato were published. In the works it was shown that the serum of rabbits and mice treated with tetanus toxin, or a person who had been ill with diphtheria, not only had the ability to inactivate a specific toxin, but also created a state of immunity when transferred to another organism. Immune serum, which had such properties, was called antitoxic. Emil von Behring was the first researcher to be awarded the Nobel Prize for discovering the medicinal properties of antitoxic serums. These works were the first to reveal to the world the phenomenon passive immunity. As T.I. figuratively put it. Ulyankin, "the treatment of diphtheria with antitoxin was the second (after Pasteur's) triumph of applied immunology."
In 1898, another Nobel laureate, Jules Bordet, a Belgian bacteriologist and immunologist who was awarded an award in 1919 for the discovery of complement, established new facts. He showed that factors that appear in the blood of infected animals and specifically bind 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 have been injected with antigens of a non-infectious nature, for example, ram erythrocytes. The serum of a rabbit that received ram erythrocytes glued only ram erythrocytes, but not erythrocytes of humans or other animals.
Moreover, it turned out that such gluing factors (in 1891 they were called by P. Ehrlich antibodies) can also be obtained by introducing foreign whey proteins under the skin or into the bloodstream of animals. This fact was established by a therapist, an infectious disease specialist and a microbiologist, a student of I. Mechnikov and R. Koch, Nikolai Yakovlevich Chistovich. Works by 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, an employee of I.I. Mechnikov, introduced the term "antigen" to designate substances that induce the formation of antibodies.
A huge contribution to the development of immunology was made by the German scientist Paul Ehrlich. He was awarded the Nobel Prize in 1908 for his discovery of humoral immunity at the same time as Ilya Ilyich Mechnikov(Fig. 4), who discovered cellular immunity: the phenomenon of phagocytosis is an active host response in the form of a cellular reaction aimed at destroying a foreign body.

Figuratively speaking, the discoveries of P. Erlich and L.I. Mechnikov likened immunology 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. Erlich is also associated with a lot of other discoveries that have survived to this day. So, they discovered mast cells and eosinophils; the concepts of "antibody", "passive immunity", "minimal lethal dose", "complement" (together with Yu. Morgenrot), "receptor" were introduced; a titration method has been developed to study the quantitative relationships between antibodies and antigens.

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

The advances made in understanding the phenomena of immunity, discoveries, brilliant conclusions and findings have not gone 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 immunological antigen-antibody reaction. These observations were developed by him in the book "Immunochemistry", written in 1907, which gave the name to a new branch of immunology.

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

anatoxin (toxoid). Anatoxins have found wide application in biology and medicine, and are still used today.

The English chemist-pathologist John Marrak in 1934, in a book devoted to a critical analysis of the chemistry of antigens and antibodies, substantiated the theory of the network (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 Niels Jerne. Biochemist Linus Pauling, another Nobel laureate (but in chemistry), one of the founders of the "direct matrix" theory of antibody formation, in 1940 described the strength of the antigen-antibody interaction and substantiated the stereophysical complementarity of reaction sites.

Michael Heidelberger (USA) is considered the founder of quantitative immunochemistry. In 1929, the Swedish chemist Arne Tiselius and the American immunochemist Alvin Kabat established by electrophoresis and ultracentrifugation that antibodies with a sedimentation constant of 19S are detected in the early period of the immune response, while antibodies with a constant of 7S are late response antibodies (later designated as antibodies of the IgM and IgG classes). respectively). In 1937, A. Tiselius suggested using the electrophoretic method to separate proteins and determined the activity of antibodies in the globulin fraction of serum. Thanks to these studies, antibodies have 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 significance of antibody bivalence and their molecular form in binding to an antigen. The works of M. Helderberger, F. Kendall and E. Kabat found that the reactions of specific precipitation, agglutination and complement fixation 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 antiserum and antigen encapsulated in agar gel. Two years later, the Swedish bacteriologist Ouchterlony and, independently of him, S.D. Elek modified Oudin's method. The gel double diffusion method they developed involved the use of agar gel-coated petri dishes with wells in the gel that allowed the antigen and antibodies placed in them to diffuse from the wells into the gel to form 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 developed a method of immunoelectrophoresis whereby an antigen, such as a serum sample, is electrophoretically separated into its constituent components before being treated with antibodies in a gel to produce precipitation bands. In 1977, the American physicist Rosalyn Yalow was awarded the Nobel Prize for the development of a radioimmunological method for the determination of peptide hormones.

Investigating the structure of antibodies, the British biochemist Rodney Porter in 1959 processed the IgG molecule with an enzyme (papain). As a result, the antibody molecule was split into 3 fragments, two of which retained the ability to bind the antigen, and the third was deprived of such ability, but easily crystallized. In this regard, the first two fragments were called Fab - or antigen-binding fragments (Fragment antigen-binding), and the third - Fe - or crystallizable fragment (Fragment crystallizable). Subsequently, it turned out that, regardless of antigen-binding specificity, antibody molecules of the same isotype of a given individual are strictly identical (invariant). In this regard, Fc fragments received a second name - constant. Currently, Fc fragments are referred to as both crystallizable (Fe - Fragment crysnallizable) and constant (Fe - Fragment constant). A significant contribution to the study of the structure of immunoglobulins was made by Henry Kunkel, Xyg Fyudenberg, Frank Putman. Alfred Nisonov found that after treatment of 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 obtained the first electron micrograph of an antibody, and somewhat later, in 1973, F.W. Putman et al published the full amino acid sequence of the IgM heavy chain. In 1969, American researcher Gerald Edelman published his data on the primary amino acid sequence of human myeloma protein (IgG) isolated from the patient's serum. Rodney Porter and Gerald Edelman were awarded the Nobel Prize in 1972 for their research.

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 Argentinean molecular biologist Cesar Milstein. The use of monoclonal antibodies has revolutionized immunology. Without their application, the functioning and further development of either fundamental or clinical immunology is unthinkable. The studies of G. Köhler and S. Milstein opened the era

Another important factor in humoral immunity are cytokines, as well as antibodies, which are products of immunocytes. However, unlike antibodies, which are characterized mainly by effector functions and, to a lesser extent, by regulatory ones, cytokines are predominantly regulatory molecules of immunity 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, in addition to antibodies, play an outstanding role in immunological reactions. The subsequent, most significant discoveries of cytokines - factors of humoral immunity, through which the functions of immunocytes - transfer factor, tumor necrosis factor, interleukin-1, interferon, a factor that suppresses macrophage migration, etc., are mediated, date back to the 30s of the 20th century.

• History of the development of immunology
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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 acted as explanations of the complex mechanisms and processes of the internal environment of a person. The presented publication will help to consider the basic concepts of the immune system, as well as to get acquainted with their founders.

Cough is a non-specific defensive reaction of the body. Its main function is to clear the respiratory tract from sputum, dust or a foreign object.

For its treatment, a natural preparation "Immunity" was developed in Russia, which is successfully used today. It is positioned as a drug to increase immunity, but relieves cough 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 disturbing the biochemical reactions of the body.

The cause of the cough is not important, whether it is a seasonal cold, swine flu, pandemic, elephant flu, no flu at all - it does not matter. An important factor is that it is a virus that affects the respiratory system. And "Immunity" copes with this best of all and is absolutely harmless!

What is the theory of immunity?

Theory of Immunity- is a doctrine generalized by experimental studies, which was 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 teachings of Mechnikov, was the concept of the German scientist P. Ehrlich. According to the teachings of P. Ehrlich, it was found that in the blood of animals infected with bacteria, microelements appear that destroy foreign particles. Protein substances are called antibodies. A characteristic feature of antibodies is their focus on resistance to a particular microbe.
• The teachings of M. F. Burnet. His theory was based on the assumption that immunity is an antibody response aimed at recognizing and separation of own and dangerous trace elements. Acts as creator clonally - selection theory of immune defense. In accordance with the presented concept, one clone of lymphocytes reacts to one specific microelement. The aforementioned theory of immunity was proven and as a result it was found that the immune reaction acts against any foreign organisms (graft, tumor).
• Instructive theory of immunity The date of creation is 1930. The founders were F. Breinl and F. Gaurowitz. According to the concept of scientists, the antigen is a place for the connection of antibodies. The antigen is also a key element of the immune response.
• The immunity theory was also developed M. Heidelberg and L. Pauling. According to the presented doctrine, compounds are formed from antibodies and antigens in the form of a lattice. The creation of a 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 in the human body there are molecules complementary to foreign microorganisms that enter the internal environment of a person. The antigen does not connect or change existing molecules. It comes into contact with its 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 established views on the functioning of the human immune system.

Cellular

The founder of the cellular (phagocytic) theory of immunity is the Russian scientist I. Mechnikov. Studying marine invertebrates, the scientist found that some cellular elements absorb foreign particles that penetrate into 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 vertebrate subjects by white cellular elements. As a result, the researcher put forward an 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.

Cells that perform protective functions in the body are called phagocytes.

When children fall ill with ARVI or the flu, they are treated mainly with antibiotics to reduce fever or various cough syrups, as well as in other ways. However, drug treatment often has a very detrimental effect on a child's body that has not yet become stronger.

It is possible to cure children from the presented ailments with the help of Immunity drops for immunity. 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, reducing the period of rehabilitation after an illness.

Distinctive features of phagocytes:

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

Mechanism of action of cellular immunity:

• In 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 - phagosome. Macrophage granules and azurophilic and specific neutrophil granules 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 the blood. The findings were presented in a unified theory of humoral immunity.

According to the author, humoral immunity is based on the principle of 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.

Nonspecific factors of the immune system represent the inherited resistance of the human body to diseases. Nonspecific 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.

You can get more information on this subject link

The merit of the researcher is to establish the fact of the transfer of antibodies by inheritance with mother's milk. As a result, a passive immune system is formed. Its duration is six months. After the child's immune system begins to function independently and develop its own cellular defense elements.

To get acquainted with the factors and mechanisms of action of humoral immunity, you can here

One of the complications of the flu and the common cold is inflammation of the middle ear. Doctors often prescribe antibiotics to treat otitis media. However, it is recommended to use the drug "Immunity". This product 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 taking the drug got rid of the disease in 1 course of use.

Immunity- this is a way to protect against living bodies and substances that carry signs of genetic alienness. This is one of the most clear and concise definitions of immunity, which belongs to R.V. Petrov.

The term immunity (immunis) was used even before our era. So, in ancient Rome, immunity was understood as exemption from paying taxes and performing duties.

The first experimental confirmation of protective mechanisms against infection was obtained by the English physician E. Jenner, who successfully vaccinated against smallpox. Later, Louis Pasteur substantiated the theory of vaccination against infectious diseases. Since that time, immunity began to be understood as immunity to infectious agents - bacteria and viruses.

The concept of immunity has been significantly expanded thanks to the work of N.F. Gamaleya - it turned out that the body has protective mechanisms against tumors and genetically alien cells. The discovery of I.I. Mechnikov, the phenomena of phagocytosis. He also proved for the first time the possibility of rejection by the body of its own old or damaged cells. The discovery of phagocytosis was the first explanation of the mechanism of destruction of pathogens by immune factors. Almost simultaneously with the discovery of cellular mechanisms, P. Ehrlich discovered humoral immunity factors, called antibodies. The beginning of clinical immunology is associated with the name of O. Bruton, who described a clinical case of hereditary agammaglobulinemia. This was the first confirmation that a deficiency of immune factors can lead to the development of human diseases.

Summarizing the accumulated data, F. Wernet in the middle of the XX century. substantiated the concept of immunity as a system that controls the constancy of the genetic composition of the organism. However, according to modern concepts, immunity does not work at the level of the genotype, but with the phenotypic manifestations of hereditary information. F. Wernet proposed a clonal-selection theory of immunity, according to which a certain antigen in the immune system is selected (selected) for a specific lymphocyte. The latter, by reproduction, creates a clone of immunocytes (a population of identical cells).

All over the world, the doctrine of immunity occupies one of the central places in the training of doctors of all specialties. This is due to the fact that the immune system, which guards antigenic homeostasis, is one of the most important adaptation systems of the body.

It is known that immune disorders naturally lead to aggravation of the course of an acute process, generalization, chronicity and recurrence of various diseases, which in turn is the cause of a number of pathological conditions. Unfavorable environmental conditions, stress, malnutrition, certain medications, surgical interventions and many other factors reduce the body's reactivity and its resistance to infectious agents.

The protective properties of the body

The first stage of self-defense of the body is represented by the skin, mucous membranes of the nose, respiratory tract, and digestive organs.

The second stage of the body's defense is represented by blood leukocytes (white blood cells).

The third stage of the body's defense against infectious diseases is the production of antibodies and antitoxins. Anti-bodies cause microbes to stick together and dissolve. Antitoxins neutralize toxic substances produced by microbes by splitting them. The property of the human body to form antibodies and antitoxins and with their help to fight pathogenic microbes in order to protect itself is called immunity.

Spleen

It is located in the upper part of the abdominal cavity, under the left rib. Its mass in an adult reaches 140-200 g.

The spleen produces lymphocytes that enter the lymphatic vessels. Lymphocytes have the ability to absorb and dissolve (phagocytize) microbes that enter the body. This means that the spleen is involved in the protection of the body from infectious diseases (in immunity). In addition, an excess of blood accumulates in the spleen, in other words, the spleen is a "blood depot". Along with this, in the spleen, there is a breakdown of worn-out formed blood elements (erythrocytes and leukocytes).

When engaging in physical labor and sports in the spleen, the formation of lymphocytes increases. And at the same time, the body's defenses (immunity) increase.

Types of immunity

Depending on the localization of action on the body, there are:

• general immunity
• local immunity

Depending on the origin, there are:

• innate immunity
• acquired immunity

According to the direction of action, there are:

• infectious immunity
• non-infectious immunity.

In a separate group allocate:

• humoral immunity
• cellular immunity
• phagocytic immunity.

General immunity

local immunity

innate immunity

Innate immunity is passed on to the child from the mother. But it is not permanent and already in the first year of a child's life loses its strength.

acquired immunity

Acquired, that is, developed by the body itself during its own life, immunity (antibodies and antitoxins), in turn, can be natural or artificial.

Active acquired immunity

Natural immunity is developed after a person has been exposed to certain infectious diseases. Artificial immunity is produced in the body of a healthy person after being vaccinated. For vaccinations in special laboratories, vaccines are made from weakened pathogenic microbes and viruses.

Natural and artificial immunity are produced in the body itself, so they are combined under the general name active immunity.

Passive acquired immunity

In addition, there is also passive immunity. After vaccination in the body of some donors, immunity is created against the causative agents of certain diseases and their toxic substances.

The famous Russian scientist I. I. Mechnikov for the first time in Russia prepared and used a vaccine and blood serum to prevent rabies, anthrax and other diseases. material from the site

infectious immunity

Infectious immunity is divided into antimicrobial and antitoxic. Antimicrobial immunity, in turn, includes antibacterial, antiviral, antifungal and antiprotozoal.

) carry out in their possessions some state functions (court, tax collection, police supervision) without the intervention of representatives of the central government; contributed to the enslavement of the peasants.

encyclopedic Dictionary. 2009 .

See what "IMMUNE (in history)" is in other dictionaries:

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Books

• Immunity. Theory, Philosophy and Experiment: Essays on the History of Immunology of the 20th Century, E.A. Aronova. 160 pages. The book is devoted to the history of modern immunology. The author examines in detail and in a new way the evolution of views on the essence of immunogenesis in the 20th century, referring to such earlier…
• Immunity. Theory, philosophy and experiment. Essays from the history of immunology of the twentieth century, E. A. Aronova. The book is devoted to the history of the formation of modern immunology. The author examines in detail and in a new way the evolution of views on the essence of immunogenesis in the 20th century, referring to such previously almost never...

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

Natural and acquired immunity

Even in ancient times, doctors were aware of human immunity 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 has suffered the disease. For example, typhoid and scarlet fever are the first infections to which doctors discovered resistance. During the disease process, the body creates antibodies that protect it from certain microbes and viruses.

The great importance of immunity is that after the cure, the body is already ready to meet re-infection. It contributes to:

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

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

A bit of history

The first inoculation was made in 1796. Edward Gener was convinced that artificially infecting smallpox with cow's blood was the best way to acquire 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 became known as sera. They became the first remedy for diseases, which gave mankind the discovery of immunity.

Serum as a last chance

If a person is ill and cannot cope with the disease on his own, he is injected with serum. It contains ready-made antibodies that the patient's body for some reason cannot produce on its own.

These are extreme measures, they are necessary only 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 gave humanity the discovery of immunity is an understanding of the work of the body as a whole. Scientists have finally understood how antibodies appear and what they are for.

Antibodies - fighters with dangerous toxins

An antitoxin is a substance that neutralizes the waste products of bacteria. It appeared in the blood only in the case of contact with 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 sections of DNA that are responsible for the synthesis of antibodies can change in every cell of the body. And they are always ready, in case of 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 covers the number of possible alien influences.

Significance 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 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 mankind, it is enough to read about life in the Middle Ages, when there were no vaccinations and sera. Look how dramatically medicine has changed, and how much better and safer life has become!