Who is the founder of the humoral theory of immunity. Who is considered the creator of the cellular theory of immunity? Cellular immunology Mechnikov

Mechnikov's theory of immunity- the theory according to which phagocytosis plays a decisive role in antibacterial immunity.

First, I.I. Mechnikov, as a zoologist, experimentally studied the marine invertebrates of the Black Sea fauna in Odessa and drew attention to the fact that certain cells (coelomocytes) of these animals absorb foreign substances (solid particles and bacteria) that had penetrated into the internal environment. Then he saw an analogy between this phenomenon and the absorption of microbial bodies by the white blood cells of vertebrates. These processes were observed by other microscopists before I.I. Mechnikov. But only I.I. Mechnikov realized that this phenomenon is not a process of nutrition of a given single cell, but is a protective process in the interests of the whole organism. I.I. Mechnikov was the first to consider inflammation as a protective rather than a destructive phenomenon. Against the theory of I.I. Mechnikov at the beginning of the 20th century. were the majority of pathologists, since they observed phagocytosis in areas of inflammation, i.e. in diseased areas, and considered white blood cells (pus) to be pathogenic rather than protective cells. Moreover, some believed that phagocytes are carriers of bacteria throughout the body, responsible for the dissemination of infections. But I.I. Mechnikov’s ideas survived; The scientist called the protective cells acting in this way “devouring cells.” His young French colleagues suggested using Greek roots of the same meaning. I.I. Mechnikov accepted this option, and the term “phagocyte” appeared. L. Pasteur was extremely pleased with these works and Mechnikov’s theory, and he invited Ilya Ilyich to work at his institute in Paris.

Mechnikov identified three important properties of phagocytes:

Protecting and cleansing properties from toxins, tissue death products, and infections;
Presenting function of antigens on the cell membrane;
A secretory property that allows the secretion of enzymes of other biological substances.

Based on these three properties of phagocytes, phagocytosis can be described as three stages:

Chemotaxis;
adhesion;
endocytosis;

In cells, the process of opsonization of the components of phagocytosis occurs. Opsonins are fixed on particles and are a link with the phagocytic cell. The main opsonins are complement components and immunoglobulins. This makes the cell highly sensitive to phagocytes and promotes their destruction.

Endocytosis promotes the formation of a phagocytic vacuole - a phagosome. Macrophage granules and azurophilic and specific neutrophil granules move to the phagosome and combine with it, releasing their contents into the phagosome tissue.

Uptake is a complex intracellular process that is enhanced by ATP-generating mechanisms, specific glycolysis and oxidative phosphorylation in macrophages.

Neutrophils have a number of microbicidal modes. The oxygen-dependent device is to increase the absorption of oxygen and glucose with the synchronous expulsion of biologically active unstable results of the resumption of oxygen supply. The oxygen-independent mechanism is combined with the vitality of key cationic proteins and lysosomal enzymes that are released into the phagosome during degranulation.

Ehrlich's theory of immunity- one of the first theories of antibody formation, according to which cells have antigen-specific receptors that are released as antibodies under the influence of an antigen.

In Paul Ehrlich's article, the author called the antimicrobial substances in the blood the term "antibody", since bacteria at that time were called the term "korper" - microscopic bodies. But P. Ehrlich “visited” a deep theoretical insight. Despite the fact that the facts of that time indicated that antibodies against a given microbe are not detected in the blood of an animal or person who has not been in contact with a specific microbe, P. Ehrlich somehow realized that even before contact with a specific microbe, the body already has antibodies in the form which he called "side chains". As we now know, this is exactly the case, and Ehrlich’s “side chains” are lymphocyte receptors for antigens that have been studied in detail in our time. Later, P. Ehrlich “applied” this same way of thinking to pharmacology: in his theory of chemotherapy, he assumed the pre-existence of receptors for medicinal substances in the body. In 1908, P. Ehrlich was awarded the Nobel Prize for the humoral theory of immunity.

Bezredky's theory of immunity- a theory that explains the body’s defense against a number of infectious diseases by the emergence of specific local cell immunity to pathogens.

Instructive theories of immunity- the general name of theories of antibody formation, according to which the leading role in the immune response is assigned to an antigen that directly participates as a matrix in the formation of a specific configuration of an antideterminant or acts as a factor that directionally changes the biosynthesis of immunoglobulins by plasma cells.



Theories of immunity - totality
scientific ideas summarizing
numerous
experimental studies, and
also futuristic concepts
formation of immunity,
development of the immune response,
functions and roles of the immune system
in the body, characteristic of
certain historical
period.

The first theoretical
parcels in this
areas supported
experimentally, were:
Cellular
(phagocytic) theory
AI. Mechnikov (1883)
Humoral theory
immunity
P. Ehrlich (1890)

Immunity issues
worked for tuberculosis
creator of the national
school of immunologists I.I.
Mechnikov.
In 1883 it was
formulated
phagocytic theory
immunity.
He showed that phagocytes
play a key role in
formation
anti-tuberculosis
immunity.

Having identified two types of leukocytes, he named one of them
macrophages. Macrophages are a necessary link in
formation of immunological tolerance.
Interaction between tubercle bacilli and
macrophages initiates the basis for tuberculosis
the process is inflammation of the granulomatous type.
One macrophage can neutralize
several dozen bacteria,
tying them together with threads of collagen.

Stages of phagocytosis
1. Stage of rapprochement.
2. Adhesion stage.
3. Absorption stage.
4. Digestion stage
Biologists of the Society's Institute of Infectious Biology
them. Max Planck managed to catch a macrophage at the moment
eating Koch bacillus, a tuberculosis pathogen.

Stages of phagocytosis

Stages of phagocytosis

P. Ehrlich (1854-1915), - the humoral
(from humor - liquid) theory of immunity. According to this theory, in
protecting the body from infection, the main role belongs to fluids,
body juices containing substances that neutralize
microbes and their poisons.
In 1891, in an article by Paul Ehrlich
antimicrobial substances in blood author
called the term "antibody". But
P. Ehrlich was “visited” by a deep
theoretical insight. Despite
that the facts of that time
testified that in the blood
not in contact with a specific
microbe of an animal or a person is not
antibodies against this
microbe, P. Ehrlich suggested that
before contact with a specific microbe in
The body already has antibodies in the form
which he called "side chains".
As we now know, this is exactly so, and
Ehrlich's "side chains" - this is in detail
currently studied receptors
lymphocytes for antigens.

Monoclonal
antibodies near the cell.

The discussion between supporters of two directions, cellular and humoral theories of immunity, continued for many years until it was clarified

Discussion between supporters of two directions, cellular and
humoral theories of immunity have continued for many
years until it became clear that both points of view complement each other
friend: both cellular,
and humoral factors. I. I. Mechnikov and P. Erlich for
were awarded the development of the doctrine of immunity in 1908.
English
scientists A. Wright and
Nobel
awards.
S. Douglas was actually reunited
theories of Mechnikov and Ehrlich in their
research into the phenomenon that
they called opsonization,
consisting in the fact that in
presence of antibodies phagocytosis
microbes increases significantly.
Opsonization - adsorption process
opsonins on the surface
microorganisms and other
foreign particles that
stimulates and facilitates phagocytosis
these particles.

Opsonization

The function of opsonins can
perform antibodies or
complement. Antibodies
bind pathogen
fragments Fa and Fb, and
Fc fragment may be
bound by specific
phagocyte receptors.
In addition to phagocytes, such
leukocytes have receptors
(monocytes, neutrophils,
eosinophils, natural
killers) who are not
phagocytose the pathogen, and, in
response to binding
pathogen, synthesize
cytokines or secrete
toxic substances,
killing
opsonized cells.
This process causes
inflammation and damage
neighboring healthy cells.
Opsonization
Neutrophil absorbing
anthrax bacterium

Neutrophil engulfs
anthrax bacillus

Immune tolerance and clonal selection theory of immunity.

As knowledge of structure and function develops
immune system it turned out that many
The body's defense reactions are not directed
only against Ag microbes, but also against cells
other organisms of the same species and even
own body.
Phagocyte destroys
bacterial cells

P. Medawar (1945) established,
that cells from an animal donor contributed
to the recipient animal
always destroyed
immune mechanisms.
This immune barrier
can only overcome
tissues taken from the body and
transplanted into the same
organism (for example,
skin grafting from the body
on hands for burns).
Peter Brian Medawar

T-lymphocyte (blue) checks cell (green)
for foreignness.
If the cell does not pass the control, the T-lymphocyte will immediately
will give the command to other cells to destroy it.

In 1953, M. Hasek established that
contact with Ag during the fetal period leads to
to the development of “unresponsiveness”
similar Ag in an adult animal.
F.M. Burnet, who substantiated the phenomenon
immune “tolerance” (tolerance).
The phenomenon itself was discovered by English
immunologist Billingham, who found that
immunization with Ag in the fetus led to
that its reintroduction
did not cause an adult animal
AT education. Thus,
contact of the body with Ag in
the antenatal period leads to
development of tolerance to it in
adulthood.
Discovery of immune tolerance
allowed us to look at it differently
the problem of organ transplantation, and
implementation into practice
immunosuppressants -
solve problems successfully
modern
F.M. Burnet

In 1908, Ilya Ilyich Mechnikov and Paul Ehrlich became 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 conducted his most significant scientific research abroad: for more than 25 years he worked in Paris, at the famous Pasteur Institute.

While studying the digestion of a starfish larva, the scientist discovered that it had special mobile cells 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, studying human immunity to tuberculosis, cholera and other infectious diseases. Mechnikov was an internationally recognized scientist, an honorary academician of six academies of sciences. He died in 1916 in Paris.

At the same time, a German scientist studied immunity problems Paul Ehrlich(1854-1915). Ehrlich's hypotheses formed the basis of the humoral theory of immunity. He suggested that in response to the appearance of a toxin 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 in the body to begin producing antibodies, receptors on the cell surface recognize the antigen. Ehrlich's ideas found their experimental confirmation a decade later.

Paul Ehrlich

Mechnikov and Ehrlich created different theories, but none of them sought to defend only their point of view. They saw that both theories were correct. It has now been proven that both immune mechanisms actually operate simultaneously in the body - Mechnikov’s phagocytes and Ehrlich’s antibodies.

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: red blood cells, white blood cells and platelets.

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

There are nonspecific innate and specific acquired immunity; in each type of immunity there are cellular and humoral components.

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

Tags: Ilya Ilyich MechnikovImmunityPaul Ehrlich

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

Created the cellular theory of immunity

In the Schools section, to the question Which scientist is considered the creator of the cellular theory of immunity? asked by the author Irina Munitsyna the best answer is The first to shed light on one of the mechanisms of immunity to infection were Behring and Kitasato. 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 laid the foundation for the study of the mechanisms of humoral immunity. The origins of the knowledge of cellular immunity were the Russian evolutionary biologist Ilya Mechnikov. In 1883, he made the first report on the phagocytic (cellular) theory of immunity at a congress of doctors and natural scientists in Odessa. Mechnikov argued then that the ability of mobile cells of invertebrate animals to absorb food particles, that is, to participate in digestion, is in fact their ability to absorb in general everything “foreign” that is not characteristic of the body: various microbes, inert particles, dying parts of the body. Humans also have amoeboid motile cells - macrophages and neutrophils. But they “eat” a special kind of food - pathogenic microbes.

Reply from 2 replies

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

Answer from LANThe origins of the knowledge of cellular immunity were the Russian evolutionary biologist Ilya Mechnikov. In 1883, he made the first report on the phagocytic (cellular) theory of immunity at a congress of doctors and natural scientists in Odessa. Mechnikov argued then that the ability of mobile cells of invertebrate animals to absorb food particles, that is, to participate in digestion, is in fact their ability to absorb in general everything “foreign” that is not characteristic of the body: various microbes, inert particles, dying parts of the body. Humans also have amoeboid motile cells - macrophages and neutrophils. But they “eat” a special kind of food - 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 protein substances appear in the blood serum of animals infected with bacteria that can kill pathogenic microorganisms. These substances were subsequently called “antibodies” by him. The most characteristic property of antibodies is their pronounced specificity. Having formed as a protective agent against one microorganism, they neutralize and destroy only it, remaining indifferent to others. Trying to understand this phenomenon of specificity, Ehrlich put forward the "side chain" theory, 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 release into circulation of only this specific receptor (antibody). Ehrlich's foresight is amazing, since with some modifications this generally speculative theory has now been confirmed. Two theories - cellular (phagocytic) and humoral - during the period of their emergence stood in antagonistic positions. The schools of Mechnikov and Ehrlich fought for scientific truth, not suspecting that every blow and every parry brought their opponents closer together. In 1908 both scientists were simultaneously awarded the Nobel Prize. The 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 “alien,” he raised the question of the importance of immune mechanisms in maintaining the genetic integrity of the organism during the period of individual (ontogenetic) development. It was 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 this theory is simple: one clone of lymphocytes is capable of responding only to one specific antigenic determinant.

Answer from Portvein777tm no the question is incorrect, this is the same as asking what is cellular caloric nor humoral im-theta, no and never was, this is bullshit, therefore - due to improper treatment, individuals so often die, read our book link

Reply from 2 replies

Hello! Here are more topics with the answers you need:

Answer the question:

Advancing immune science | Meddoc

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

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

Edward Jenner

Creation of vaccines

The Englishman Edward Jenner (1749-1823) can be considered a pioneer in this area, who managed to rid humanity of smallpox. While 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 blisters formed on their udders, strongly reminiscent of smallpox. During milking, the liquid contained in these bubbles was often rubbed into people's skin, but milkmaids rarely suffered from smallpox. Jenner was unable to give a scientific explanation for this fact, since the existence of pathogenic microbes was not yet known. As it turned out later, the smallest microscopic creatures - the viruses that cause cowpox - are somewhat different from those viruses that infect humans. However, the human immune system also reacts to them.

In 1796, Jenner inoculated a fluid taken from cow pockmarks into a healthy eight-year-old boy. He felt slightly ill, which soon went away. A month and a half later, the doctor inoculated him with human smallpox. But the boy did not get sick, because after the vaccination his body developed antibodies, 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 no longer get sick from this disease. His immunity is working, 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 affects dogs, wolves, foxes and many other animals. In this case, the cells of the nervous system suffer. The sick person develops hydrophobia - it is impossible to drink, because water causes convulsions of the pharynx and larynx. Death may occur due to paralysis of the respiratory muscles or cessation of cardiac activity. Therefore, if a dog or other animal is bitten, it is necessary to immediately undergo a course of vaccinations against rabies. The serum, created by a French scientist in 1885, is successfully used to this day.

Immunity against rabies only lasts 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, the body produces protective substances - antibodies. Based on this discovery, the German scientist Paul Ehrlich (1854-1915) created the humoral theory of immunity: foreign bodies are eliminated by antibodies - chemicals delivered by the blood. If phagocytes can destroy any antigens, then antibodies can only destroy those against which they were produced. Currently, reactions of antibodies with antigens are used in the diagnosis of various diseases, including allergic ones. In 1908, Ehrlich, together with Mechnikov, was awarded the Nobel Prize in Physiology or Medicine “for his work on the theory of immunity.”

Further development of immunology

At the end of the 19th century, it was found that when transfusing blood, it is important to take into account its group, since normal foreign cells (erythrocytes) are also antigens for the body. The problem of 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 sends antibodies and lymphocytes to fight them. It was only in 1953, when the opposite phenomenon of immunity was discovered - immunological tolerance (loss or weakening of the body's ability to respond to a given antigen) that transplantation operations became significantly more successful.

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

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

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

Who discovered the mechanisms of immunity?

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

In this 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 rocketry. He justified the main principles. The world's first Soviet satellites, and then American ones, launched by other people after the death of the father of rocket navigation, did not overshadow the significance of his work.

“From the most ancient to the most recent times, it was taken for granted that the body has some ability to react against harmful influences entering it from the outside. This ability of resistance has been called differently. 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.” This is what the magazine “Russian Medicine” said about the report of Ilya Ilyich Mechnikov at the Society of Kyiv Doctors, made on January 21, 1884.

Of course not. The report formulated thoughts that were born in the scientist’s head much earlier, during his work. By that time, certain elements of the theory had already been published in articles and reports. But we can call this date the birthday of the great discussion 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 Metchnikoff. 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 fight 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 conducted 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 counter-attacks of opponents. The weapons were facts. Just the facts.

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

Dozens of experiments followed. Foreign particles - splinters, grains of paint, bacteria - are captured by moving cells. Under a microscope you can see how cells gather around uninvited aliens. Part of the cell extends in the form of a promontory - a false leg. In Latin they are called “pseudopodia”. Foreign particles are covered by pseudopodia and end up inside the cell, as if devoured by it. Mechnikov called these cells phagocytes, which means eater cells.

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

The most interesting thing, of course, is the phagocytosis of bacteria.

Here is a scientist injecting anthrax pathogens into frog tissue. Phagocytes flock to the site of microbial introduction. Each captures one, two, or even a dozen bacilli. The cells devour these sticks and digest them.

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

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

And the argument began...

1887 International Hygiene Congress in Vienna. Mechnikov’s phagocytes and his theory are talked about only in passing, as something completely implausible. Munich bacteriologist, student of hygienist Max Pettenkofer, Rudolf Emmerich, reports in his report that he injected immune, that is, previously vaccinated, pigs with the rubella microbe, and the bacteria died within an hour. They died without any intervention from phagocytes, which during this time did not even have time to “swim” to the microbes.

What is Mechnikov doing?

He does not scold his opponent or write pamphlets. He formulated his phagocytic theory before he saw that rubella microbes were being consumed by cells. He does not call on authorities for help. He replicates Emmerich's experience. The Munich colleague was mistaken. Even after four hours, the germs 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 exactly the time that phagocytes need to work. In 1891, Emmerich published self-refuting articles.

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

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

It is possible to artificially develop such immunity. And the serum of this animal must kill the corresponding microbes. Bering created antitetanus serum. To obtain it, he injected rabbits with the poison of tetanus bacilli, gradually increasing its dose. Now we need to test the strength of this serum. Infect a rat, rabbit or mouse with tetanus, and then inject antitetanus 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 this is exactly how diphtheria began to be treated in children and is still treated today, using the serum of previously immunized horses. In 1901, Bering received the Nobel Prize for this.

But what does this have to do with the eater cells? They injected serum, part of the blood where there are no cells. And the serum helped fight germs. No cells, no phagocytes entered the body, and yet it 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. This means that the humoral theory is correct. The phagocytic theory is incorrect.

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

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

Humoral mechanisms still operate in the fight against microbes; they exist. After Bering's studies, we have to agree that contact of the body with microbial bodies leads to the accumulation of antibodies circulating in the blood. (A new concept has appeared - antibody; more about antibodies will be later.) Some microbes, such as Vibrio cholera, 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 bear the main job of capturing and destroying bacteria.

1894 Budapest. The next international congress. And again Mechnikov’s passionate polemic, but this time with Pfeiffer. The cities changed, the topics discussed in the dispute changed. The discussion led further into the depths of the complex relationships between animals and microbes.

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

“To this day 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 evoked applause from the audience. New facts, which at first seemed to contradict the phagocytic theory, soon came into harmonious combination with it.”

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

15 years of dispute. 15 years of mutual refutations 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. The opponents moved forward throughout the war in one direction. This kind of war is good!

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

Next chapter >

bio.wikireading.ru

Theory of immunity - Chemist's Handbook 21

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

The model theory of immunity is presented in 17.10.

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

BURNET F. Integrity of the body (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 was stated earlier. Here it is only appropriate to emphasize that it was the foundation for the study of cellular immunity and essentially created the prerequisites for the formation of an understanding 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, for example, cancer cells or cells affected by viruses. But until recently it was not known exactly how lymphocytes do this. Lately this has become clear.

The existence on the surface of cells of proteins capable of selectively binding various substances from the environment surrounding the cell was predicted at the beginning of the century by Paul Ehrlich. This assumption formed the basis of his famous theory of side chains - one of the first theories of immunity, significantly 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 plant defense reactions. The book shows that changes in the functioning of the cell's enzymatic apparatus are a consequence of the influence of the pathogen on the activity of all the most important centers of cell activity, including the nuclear apparatus, ribosomes, mitochondria and chloroplasts.

The workings of this complex and surprisingly expedient mechanism have long been of concern to researchers. Since the time of the dispute between Mechnikov (a supporter of the cellular theory of immunity) and Ehrlich (a supporter of the humoral, serum theory), in which, as usual, both were right (and both were simultaneously awarded the Nobel Prize), and to this day a huge number of different 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 antibody accumulation 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 small and very high concentrations of the antigen; the ability to distinguish self from foreign; i.e., the absence of a reaction to host tissue, and autoimmune diseases, when such a reaction still occurs; immunological reactivity in cancer and insufficient effectiveness of the immune system when cancer manages to escape the body's control.

The creator of the cellular theory of immunity is I. I. Mechnikov, who in 1884 published a work on the properties of phagocytes and the role of these cells in the immunity of organisms to bacterial infections. Almost simultaneously, the so-called humoral theory of immunity 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 re-enter the body. In 1901, P. Ehrlich, having analyzed and generalized the data accumulated in the humoral direction, created a theory of antibody formation. Many years of fierce polemics between I.I. Mechnikov and a group of leading microbiologists of that time led to a comprehensive testing of both theories and their complete confirmation. In 1908, the Nobel Prize in Medicine was awarded to I. I. Mechnikov and P. Ehrlich as the creators of the general theory of immunity.

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

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

Arrhenius sent copies of his thesis to other universities, and Ostwald in Riga, as well as Van't Hoff in Amsterdam, praised it. OtbaJIBD visited Arrhenius and offered him a position at his university. This support and the experimental confirmation of Arrhenius's theory changed the attitude towards him in his homeland. 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 Physicochemical Institute of the Nobel Committee. Arrhenius launched a large research program in the field of physical chemistry. His interests covered problems as far apart as ball lightning, the influence 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 the Latin humor - liquid) theory of immunity. He believed that immunity arises as a result of the formation of antibodies in the blood that neutralize the poison. This was confirmed by the discovery of antitoxins - antibodies that neutralize toxins in animals that were injected with diphtheria or tetanus.

This central position of the clonal selection theory of immunity has caused great debate for many years. The predetermination towards antigens that the body encountered during phylogenesis was clear, but doubts arose whether there really were T-lymphocytes with receptors for new (synthetic and chemical) antigens, the emergence of which in nature was associated with the development of technological progress in the 20th century. However, special studies carried out using the most sensitive serological methods have revealed normal antibodies to a number of chemical haptens - dinitrophenyl, 3-iodo-4-hydroxyphenylacetic acid, etc. - in humans and more than 10 species of mammals. Apparently, the three-dimensional structures of receptors are indeed very diverse, and in the body there can always be several cells whose receptors are quite close to the new determinant. It is possible that the final grinding of the receptor to the determinant can occur after their connection during the process of differentiation of T lymphocytes into T lymphocytes after meeting its antigen, the T cell, through 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, and are sensitive to the action of anti-0, antithymocyte and antilymphocyte sera. These lymphocytes form the central link of the immune system. After the formation of a clone, i.e., reproduction by division into morphologically identical, but functionally heterogeneous cells, T lymphocytes actively participate in the formation of the immune response.

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

Despite the successes of infectious immunology, experimental and theoretical immunology remained in a rudimentary state 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 and the biological range of action of immunity remained unknown to the researcher.

The new stage in the development of immunology is associated primarily with the name of the emerging Australian scientist M.F. Burnet. It was he who largely determined the face of modern immunology. Considering immunity as a reaction aimed at differentiating everything that is one’s own from everything that is foreign, he raised the question of the importance of immune mechanisms in maintaining the genetic integrity of the organism during the period of individual (ontogenetic) development. It was Wernet who drew attention to the lymphocyte as the main participant in a specific immune reaction, giving it the name immunocyte. It was Vernet who predicted, and the Englishman Peter Medavar and the Czech Milan Hasek experimentally confirmed the state opposite to immune reactivity - tolerance. It was Wernet 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 this theory is simple: one clone of lymphocytes is capable of reacting only to one specific, antigenic, specific determinant.

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

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

During the immunological period of 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 theory

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 proven that under the influence of antigens, B cells turn into plasma cells, and several diverse subpopulations arise from undifferentiated T cells. In 1966, cytokines of T-lymphocytes were discovered, which determine the cooperation (interaction) of immunocompetent cells. Thus, the cell-humoral theory of immunity of Mechnikov-Ehrlich received a comprehensive justification, and immunology - the basis for an in-depth study of the specific mechanisms of individual 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 is caused by the introduction of not only living, but also killed microbes. Inoculation of pigeons with heated bacilli, the causative agents of swine cholera, caused a state of immunity to the virulent culture of microbes. Moreover, they suggested that the state of immunity can also be induced by introducing into the body chemical substances or toxins produced by bacteria that cause 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 body fluids. The German bacteriologist Hans Buchner continued these studies and named the heat-sensitive bactericidal factor of cell-free serum alexin, later called complement by Ehrlich and Morgenroth. Employees of the Pasteur Institute (France) Emile Py and Alexandre Yersin found that the cell-free filtrate of a culture of diphtheria bacillus contains an exotoxin that can induce the disease. In December 1890, Karl Frenkel published his observations indicating the induction of immunity using a heat-killed broth culture of diphtheria bacillus. In December of the same year, the works of the German bacteriologist Emil von Behring and the Japanese bacteriologist and researcher Shibasaburo Kitasato were published. The works showed that the serum of rabbits and mice treated with tetanus toxin, or a person who had suffered from 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 that had such properties was called antitoxic. Emil von Behring was the first researcher to be awarded the Nobel Prize for his discovery of the medicinal properties of antitoxic serums. These works were the first to reveal the phenomenon to the world passive immunity. As T.I. figuratively put it. Ulyankin, “the treatment of diphtheria with antitoxin became the second (post-Pasteur) triumph of applied immunology.”
In 1898, another Nobel laureate, Jules Bordet, a Belgian bacteriologist and immunologist who had been awarded the prize in 1919 for the discovery of complement, established new facts. He showed that factors that appear in the blood of infected animals and specifically glue infections are found in the blood of animals immunized not only with microbes or their toxin products, but also in the blood of animals that were injected with antigens of a non-infectious nature, for example, sheep erythrocytes. The serum of a rabbit that received sheep red blood cells glued only sheep red blood cells, but not human or other animal red blood cells.
Moreover, it turned out that such gluing factors (in 1891 they were called by P. Ehrlich antibodies) can also be obtained by injecting foreign whey proteins under the skin or into the bloodstream of animals. This fact was established by a therapist, infectious disease specialist and 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.
The German scientist Paul Ehrlich made a huge contribution to the development of immunology. In 1908 he was awarded the Nobel Prize for the discovery of humoral immunity at the same time as Ilya Ilyich Mechnikov(Fig. 4), who discovered cellular immunity: the phenomenon of phagocytosis is an active response of the host in the form of a cellular reaction aimed at destroying a foreign body.

Figuratively speaking, the discoveries of P. Ehrlich and L.I. Mechnikov 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 is “cellular immunity”.

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

P. Ehrlich (Fig. 5) put forward a dualistic concept of hematopoiesis, according to which he proposed to distinguish between lymphoid and myeloid hematopoiesis; together with J. Morgenroth in 1900, based on the erythrocyte antigens of goats, he described their blood groups. He established that immunity is not inherited, since immune parents give birth to non-immune offspring; 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 (studying the mechanisms of autoimmunity); substantiated the presence of anti-antibodies.

The achievements 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 introduced the term in his lectures on the chemistry of immunological reactions at the University of California at Berkeley.

"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 the new branch of immunology.

Gaston Ramon, an employee of the Pasteur Institute in Paris, treated diphtheria toxin with formaldehyde and discovered that the drug deprived it of its toxic properties without disturbing its specific immunogenic ability. This drug was named

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

In 1934, the English chemical pathologist John Marrack, in a book devoted to a critical analysis of the chemistry of antigens and antibodies, substantiated the lattice network theory of their interaction. The theory of network (idiotypic) regulation of immunogenesis by antibodies was subsequently developed and created by the Nobel laureate (in immunology) Danish immunologist Nils Erne. Biochemist Linus Pauling, another Nobel laureate (but in chemistry), one of the founders of the “direct matrix” theory of antibody formation, in 1940 described the strength of 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, using electrophoresis and ultracentrifugation methods, established that antibodies with a sedimentation constant of 19S are detected in the early period of the immune response, while antibodies with a constant of 7S are antibodies of a late response (later designated as antibodies of the IgM and IgG classes respectively). In 1937, A. Tiselius proposed using the electrophoretic method to separate proteins and determined the activity of antibodies in the globulin fraction of serum. Thanks to these studies, antibodies received the status

immunoglobulins. In 1935, M. Heidelberger and F. Kendall functionally characterized monovalent or partial antibodies as non-precipitating, D. Presman and Campbell obtained rigorous evidence for the importance of the bivalence of antibodies and their molecular form in binding to antigen. The work of M. Helderberger, F. Kendall and E. Kabat established that the reactions of specific precipitation, agglutination and complement fixation are different manifestations of the functions of individual antibodies. Continuing research on antibodies, in 1942, American immunologist and bacteriologist Albert Coons demonstrated 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 embedded in an agar gel. Two years later, the Swedish bacteriologist Ouchterlon and, independently of him, S.D. Elek modified the Oudin method. The double gel 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 and 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 technique called immunoelectrophoresis, in which an antigen, such as a serum sample, is electrophoretically separated into its constituent components before reacting with antibodies in a gel to produce precipitation bands. In 1977, American physicist Rosalyn Yalow was awarded the Nobel Prize for developing a radioimmunological method for the determination of peptide hormones.

While studying the structure of antibodies, British biochemist Rodney Porter treated the IgG molecule with an enzyme (papain) in 1959. As a result, the antibody molecule was split into 3 fragments, two of which retained the ability to bind antigen, and the third was deprived of this ability, but easily crystallized. In this regard, the first two fragments were 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 called both crystallizable (Fe - Fragment crysnallizable) and constant (Fe - Fragment constant). Significant contributions to the study of the structure of immunoglobulins were made by Henry Kunkel, Xyg Fudenberg, and Frank Putman. Alfred Nisonov found that after treating an 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 a little later - in 1973, F.W. Putman et al published the complete amino acid sequence of the IgM heavy chain. In 1969, American researcher Gerald Edelman published data on the primary amino acid sequence of human myeloma protein (IgG), isolated from patient 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 based on them. The methodology was developed by German immunologist Georg Köhler and Argentine molecular biologist Cesar Milstein. The use of monoclonal antibodies has revolutionized immunology. Without their use, the functioning and further development of either fundamental or clinical immunology is unthinkable. The research of G. Köhler and S. Milstein opened the era

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

• History of the development of immunology
• We summed up the first results of the activities of information and advisory teams this year
• Breeding peacocks in the Russian climate
• A new site for processing meat products was opened in the Nenets Autonomous Okrug
• The Stavropol Territory is reviving pig farming
• The festival “Golden Autumn - 2015” is an important stage in acquiring new knowledge and skills for agricultural workers
• City quest adventures from Street Adventure: discover the secrets of the capital
• The Governor of the Tambov Territory visited the Pokrovsk Fair
• The Prime Minister of the Russian Federation personally visited the exhibition of goods of the Tambov region
• Goat farming and cheese production
• Courses for rural entrepreneurs are starting in the Tomsk region
• Comparison of wooden decking boards and WPC
• The prospects for the use of peat resources were discussed in the Tomsk region
• Hundreds of young specialists managed to find employment in agricultural companies in the Ryazan region
• Active field work is underway in the Ivanovo region
• In the Omsk region, grain storage capacity is being increased in difficult weather conditions.
• Producers of agricultural goods in the Tambov region discussed prospects for the development of the industry
• A scientific and practical conference dedicated to the development of vegetable growing was held in the Moscow region
• Agricultural producers of the Digori region held a meeting with the Acting Minister of Agriculture of North Ossetia
• In the Omsk region, a special commission spoke about the results of the first stage of preparation for the national census
• The Strategy for the Development of the Agro-Industrial Complex was discussed in the Leningrad region
• Reliable and high-quality products from DEFA
• Cleaning and disinfection of clothes for all occasions
• An important meeting was held in the Orenburg region at the John Deere base
• Compensation for stocking of fish will take place in Chelyabinsk
• A ton of sugar beets was processed at factories in Lipetsk
• Nikolay Pankov promised to solve the problem of installing tachographs
• The first results of the harvesting campaign were discussed in the Vologda region
• The head of the Ministry of Agriculture of Stavropol told how to get away from bureaucratic procedures
• The Indian Summer harvest fair was held in the Omsk region

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 of the science. Theoretical teachings acted as explanations for the complex mechanisms and processes of the human internal environment. The presented publication will help you consider the basic concepts of the immune system, as well as get acquainted with their founders.

Cough is a nonspecific protective reaction of the body. Its main function is to clear the airways of mucus, dust or foreign objects.

For its treatment, a natural drug “Immunity” was developed in Russia, which is successfully used today. It is positioned as a drug to improve immunity, but it eliminates cough 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 flu, or elephant flu at all - it does not matter. An important factor is that this is a virus that affects the respiratory system. And “Immunity” copes with this best and is absolutely harmless!

What is the theory of immunity?

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

Basic theories of immunity

The 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. 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 I.I. Mechnikov. In 1883, a representative of the Russian scientific community proposed the concept according to which mobile cellular elements are present in the internal environment of a person. They are able to swallow and digest foreign microorganisms throughout their body. 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 concept of the German scientist P. Ehrlich. According to the teachings of P. Ehrlich, it was found that microelements appear in the blood of animals infected with bacteria, destroying foreign particles. Protein substances are called antibodies. A characteristic feature of antibodies is their focus on resistance to a specific microbe.
• The 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 microelements. Serves as creator clonal - selection theory of immune defense. In accordance with the presented concept, one clone of lymphocytes reacts to one specific microelement. The indicated theory of immunity was proven and as a result it was revealed that the immune reaction acts against any foreign organisms (graft, tumor).
• Instructive theory of immunity The date of creation is considered to be 1930. The founders were F. Breinl and F. Gaurowitz. According to the concept of scientists, an antigen is a site for antibodies to connect. Antigen is also a key element of the immune response.
• The theory of immunity was also developed M. Heidelberg and L. Pauling. According to the presented teaching, compounds are formed from antibodies and antigens in the form of a lattice. The creation of a lattice will be possible only if the antibody molecule contains three determinants for the antigen 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 bind 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 regarding the functioning of the human immune system.

Cellular

The founder of the cellular (phagocytic) theory of immunity is the Russian scientist I. Mechnikov. While studying marine invertebrates, the scientist found that some cellular elements absorb foreign particles that penetrate into the internal environment. Mechnikov's merit lies in drawing an analogy between the observed process involving invertebrates and the process of absorption of white cellular elements from the blood of vertebrate subjects. As a result, the researcher put forward the opinion that 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 influenza, they are treated mainly with antibiotics to reduce the temperature or various cough syrups, as well as in other ways. However, drug treatment often has a very detrimental effect on a child’s body, which has not yet become stronger.

It is possible to cure children from these ailments with the help of “Immunity” drops. It kills viruses in 2 days and eliminates secondary symptoms of influenza and acute respiratory viral infections. And in 5 days it removes toxins from the body, shortening the rehabilitation period after illness.

Distinctive features of phagocytes:

• Implementation of protective functions and removal of toxic substances from the body;
• Presentation of antigens on the cell membrane;
• Isolation of a chemical substance 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 occurs. The presented process contributes to the elimination of foreign elements;
• Endocytosis influences the creation of a phagocytic vacuole - a phagosome. Macrophage granules and azurophilic and specific neutrophil granules move to the phagosome and combine with it, releasing their contents into the phagosome tissue;
• During the absorption process, 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, the basis of humoral immunity is the principle of destruction of foreign elements through fluids of the internal environment (through blood). Substances that carry out the process of eliminating viruses and bacteria are divided into two groups - specific and nonspecific.

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 detailed information on this issue link

The merit of the researcher lies in establishing the fact of inheritance of antibodies through mother's milk. As a result, a passive immune system is formed. Its duration is six months. Afterwards, the child’s immune system begins to function independently and produce its own cellular defense elements.

You can get acquainted with the factors and mechanisms of action of humoral immunity here

One of the complications of flu and colds is inflammation of the middle ear. Often, doctors prescribe antibiotics to treat otitis media. However, it is recommended to use the drug “Immunity”. This product was developed and passed clinical trials 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 within 1 course of use.

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 occurred, to evaluate its results, the scientific community and society as a whole sometimes require 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 outstanding scientists who put forward hypotheses, made discoveries and formulated theories, and some of these theories and discoveries were made a hundred years ago.

Two schools, two theories

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

Immunology as a science emerged 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 the answer to the survival of the human race, despite the regular devastating epidemics of plague, smallpox, cholera, falling on countries and continents like the punishing sword of fate. Millions, tens of millions of dead. But in cities and villages where funeral teams did not have time to remove corpses from the streets, there were those who independently, without the help of healers and sorcerers, coped with the deadly scourge. 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 external invasions. 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 one is more important? Which one plays a role in successful vaccination? At the beginning of the twentieth century, in answering this fundamental question, two theories, two schools - those of Paul Ehrlich and Ilya Mechnikov - collided in a heated scientific debate.

Paul Ehrlich has never been to Kharkov or Odessa. He attended 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 of Experimental Therapy in Frankfurt am Main, which today bears his name. And here it should be recognized that, conceptually, Ehrlich has done more for immunology in the entire history 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 foreign to the body. It is this mechanism, he believed, that is the main one in the immune system, building lines of defense against invading pathogens. It is the phagocytes that rush to attack, causing an inflammatory reaction, for example, with an injection, a splinter, etc.

Ehrlich 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 is called the theory of humoral immunity.

It is interesting that irreconcilable scientific rivals - Mechnikov and Ehrlich - shared the Nobel Prize in Physiology or Medicine in 1908 for their work in the field of immunology, although by this time the theoretical and practical successes of Ehrlich and his followers seemed to completely refute the views of Mechnikov. It was even rumored that the prize was awarded to the latter, rather, based on 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 came only a century later.

Ehrlich died in 1915, Mechnikov outlived his opponent by only a year, so the most fundamental scientific dispute developed until the end of the century without the participation of its initiators. In the meantime, everything that happened in immunology over the next decades confirmed that Paul Ehrlich was right. 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 mid-twentieth century took the science of acquired immunity to a completely different level - the founders could not have foreseen this). They are the ones who organize protection from viruses, microbes, fungi and, in general, from substances hostile to the body. B lymphocytes produce antibodies that bind the foreign protein, neutralizing its activity. And T-lymphocytes destroy infected cells and help remove the pathogen from the body in other ways, and in both cases a “memory” of the pathogen is formed, so that it is much easier for the body to fight re-infection. These protective lines are able to deal in the same way with their own, but degenerated protein, which becomes dangerous for the body. Unfortunately, such an ability, in the event of a failure in setting up the complex mechanism of adaptive immunity, can become the cause of autoimmune diseases, when lymphocytes, having lost the ability to distinguish their own proteins from foreign ones, begin to “shoot at their own”...

Thus, until the 80s of the twentieth century, immunology mainly developed along the path indicated by Ehrlich, and not by Metchnikoff. Incredibly complex, fantastically sophisticated over 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 obtained 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 negating their beneficial functions, but medicine noticed this and sounded the alarm much, much later...

However, the frontiers of 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 devoid of adaptive immunity (in evolution, it appears only at 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 the human microflora contains 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 begin

In 1989, American immunologist Professor Charles Janeway ( Charles Janeway) published a work that was very soon recognized as visionary, although, like Mechnikov’s theory, it had and still has serious, erudite opponents. Janeway suggested that on human cells responsible for immunity, there are 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, Janeway suggested that the receptors would also recognize some “invariant” chemical structures characteristic of a whole class of pathogens. Otherwise there simply won’t be enough genes!

A few years later, Professor Jules Hoffmann (who later became president of the French Academy of Sciences) discovered that the fruit fly - an almost indispensable participant in the most important discoveries in genetics - has a defense system that was 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 larvae, but is also associated with innate immunity. If this gene is spoiled in a fly, then it dies when infected with fungi. Moreover, it will not die from other diseases, for example, of a bacterial nature, but inevitably from a fungal one. The discovery allowed us to draw three important conclusions. First, the primitive fruit fly is endowed with a powerful and effective innate immune system. Secondly, its cells have receptors that recognize infections. Thirdly, the receptor is specific to a certain class of infections, that is, it is capable of recognizing not any foreign “structure,” but only a very specific one. But 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. Then, as happens in science, events developed progressively. Ruslan Medzhitov, who graduated from Tashkent University, then graduate school at Moscow State University, and later became a professor at Yale University (USA) and a rising star in world immunology, was the first to discover these receptors on human cells.

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

In fact, a conceptual revolution took place. It turned out that for everyone on Earth, innate immunity is the main one. And only the most “advanced” organisms on the ladder of evolution - higher vertebrates - acquire acquired immunity in addition. However, it is the innate that directs its initiation and subsequent operation, although many of the details of how all this is regulated have yet to be established.

"His Excellency's adjuvant"

New views on the interaction of the innate and acquired branches of immunity have helped to understand what was previously unclear.

How do vaccines work when they work? In general (and very simplified) form, it goes something like this. A weakened pathogen (usually a virus or bacteria) is injected into the blood of a donor animal, such as a horse, cow, rabbit, etc. The animal's immune system produces a protective response. If the protective response is associated with humoral factors - antibodies, then its material carriers can be purified and transferred into the human blood, simultaneously transferring the protective mechanism. In other cases, the person himself is infected or immunized with a weakened (or killed) pathogen, hoping to provoke an immune response that can protect against the real pathogen and even become entrenched in cellular memory for many years. This is how Edward Jenner, at the end of the 18th century, was the first in the history of medicine to vaccinate 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, many simple chemical compounds or proteins that are foreign to the body and would simply have to initiate a response from the immune system do not respond! And this often happens for the reason that the mechanism of the main defender - innate immunity - remains unawakened.

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

Freund's discovery was purely experimental and therefore may seem private. But Janeway sensed in it a moment of general significance. Moreover, he even called the inability to induce a full-fledged immune response to a foreign protein in experimental animals or in humans “the 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).

Janeway suggested that the innate immune system recognizes bacteria (both live and dead) by the components of their cell walls. Bacteria that live “on their own” need strong multilayer cell walls for external protection. Our cells, under a powerful cover of external protective tissues, do not need such shells. And bacterial membranes are synthesized with the help of enzymes that we do not have, and therefore the components of bacterial walls are precisely those chemical structures, ideal indicators of the threat of infection, for which the body, in the process of evolution, has produced recognition receptors.

It turned out that the walls of mycobacteria - namely, tuberculosis bacilli - are particularly 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, sending it a false signal that the body is infected with a dangerous pathogen. Force a reaction. But in fact, there is no such pathogen in the vaccine at all or it is not so dangerous

There is no doubt that it will be possible to find other, including non-natural, adjuvants for immunizations and vaccinations. This new direction of biological science is of enormous importance for medicine.

Turn on/off the desired gene

Modern technologies make it possible to turn off (“knockout”) the only gene in an experimental mouse that encodes one of the innate immune receptors. For example, responsible for recognizing the same gram-negative bacteria. Then the mouse loses the ability to provide its defense and, being infected, dies, although all other components of its immunity are not impaired. This is exactly how the work of immune systems at the molecular level is studied experimentally 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 with mutations in specific genes. For hundreds of years, examples have been known when in some families, clans and even tribes there was an extremely high mortality rate of children at an early age from very specific diseases. It now becomes clear that in some cases the cause is a mutation of some component of the innate immune system. The gene is turned off - partially or completely. Since most of our genes are in two copies, we must make special efforts to ensure that both copies are damaged. This can be “achieved” as a result of consanguineous 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 reason 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 immune 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 layer of protection, he will be able to cope with the threat and possibly live a full life. The danger will remain, but its level will decrease significantly. There is still hope that one day gene therapy will become part of everyday practice. Then the patient will simply need to transfer the “healthy” gene, without mutation. In mice, scientists can not only turn off a gene, but also turn it on. In humans it is much more difficult.

About the benefits of curdled milk

It is worth remembering one more foresight of I.I. Mechnikov. A hundred years ago, he connected the activity of phagocytes he discovered 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 digestion process. 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 innate immune receptors, bacteria send the body some “tonic” signals, 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 intestines, 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 (is it the last?) revolution in immunology is too short a period for the widespread 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 conducts development without taking into account new knowledge about the mechanisms of innate immunity. And some practical successes have already been achieved, 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. There is no need to doubt this. You just have to wait a little.

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

“Science and Life” about immunity:
1) Petrov R. Right on target. - 1990, № 8.
2) Mate J. A person from the point of view of an immunologist. - 1990, № 8.
3) Belokoneva O. Immunity in retro style . - 2004, № 1.
4) Zverev V. Vaccines from Jenner and Pasteur to the present day . - 2006, № 3.
5) Tchaikovsky Yu. Jubilee of Lamarck-Darwin and the revolution in immunology. - 2009, №№ , , , .

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 occurred, to evaluate its results, the scientific community and society as a whole sometimes require 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 outstanding 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, mutant for the Toll gene, became overgrown with fungi and died, since it does not have immune receptors that recognize fungal infections.

Two schools, two theories

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

Immunology as a science emerged 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 the answer to the survival of the human race, despite the regular devastating epidemics of plague, smallpox, cholera, falling on countries and continents like the punishing sword of fate. Millions, tens of millions of dead. But in cities and villages where funeral teams did not have time to remove corpses from the streets, there were those who independently, without the help of healers and sorcerers, coped with the deadly scourge. 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 external invasions. 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 one is more important? Which one plays a role in successful vaccination? At the beginning of the twentieth century, in answering this fundamental question, two theories, two schools - those of Paul Ehrlich and Ilya Mechnikov - collided in a heated scientific debate.

Paul Ehrlich has never been to Kharkov or Odessa. He attended 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 of Experimental Therapy in Frankfurt am Main, which today bears his name. And here it should be recognized that, conceptually, Ehrlich has done more for immunology in the entire history 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 foreign to the body. It is this mechanism, he believed, that is the main one in the immune system, building lines of defense against invading pathogens. It is the phagocytes that rush to attack, causing an inflammatory reaction, for example, with an injection, splinter, etc.

Ehrlich 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 is called the theory of humoral immunity.

It is interesting that irreconcilable scientific rivals - Mechnikov and Ehrlich - shared the Nobel Prize in Physiology or Medicine in 1908 for their work in the field of immunology, although by this time the theoretical and practical successes of Ehrlich and his followers seemed to completely refute the views of Mechnikov. It was even rumored that the prize was awarded to the latter, rather, based on 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 came only a century later.

Ehrlich died in 1915, Mechnikov outlived his opponent by only a year, so the most fundamental scientific dispute developed until the end of the century without the participation of its initiators. In the meantime, everything that happened in immunology over the next decades confirmed that Paul Ehrlich was right. 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 mid-twentieth century took the science of acquired immunity to a completely different level - the founders could not have foreseen this). They are the ones who organize protection from viruses, microbes, fungi and, in general, from substances hostile to the body. B lymphocytes produce antibodies that bind the foreign protein, neutralizing its activity. And T-lymphocytes destroy infected cells and help remove the pathogen from the body in other ways, and in both cases a “memory” of the pathogen is formed, so that it is much easier for the body to fight re-infection. These protective lines are able to deal in the same way with their own, but degenerated protein, which becomes dangerous for the body. Unfortunately, such an ability, in the event of a failure in setting up the complex mechanism of adaptive immunity, can become the cause of autoimmune diseases, when lymphocytes, having lost the ability to distinguish their own proteins from foreign ones, begin to “shoot at their own”...

Thus, until the 80s of the twentieth century, immunology mainly developed along the path indicated by Ehrlich, and not by Metchnikoff. Incredibly complex, fantastically sophisticated over 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 obtained 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 negating their beneficial functions, but medicine noticed this and sounded the alarm much, much later...

However, the frontiers of 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 devoid of adaptive immunity (in evolution, it appears only at 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 the human microflora contains 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 begin

In 1989, the American immunologist Professor Charles Janeway published a work that was very quickly recognized as visionary, although, like Metchnikoff’s theory, it had and still has serious, erudite opponents. Janeway suggested that on human cells responsible for immunity, there are 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, Janeway suggested that the receptors would also recognize some “invariant” chemical structures characteristic of a whole class of pathogens. Otherwise there simply won’t be enough genes!

A few years later, Professor Jules Hoffmann (who later became president of the French Academy of Sciences) discovered that the fruit fly - an almost indispensable participant in the most important discoveries in genetics - has a defense system that was 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 larvae, but is also associated with innate immunity. If this gene is spoiled in a fly, then it dies when infected with fungi. Moreover, it will not die from other diseases, for example, of a bacterial nature, but inevitably from a fungal one. The discovery allowed us to draw three important conclusions. First, the primitive fruit fly is endowed with a powerful and effective innate immune system. Secondly, its cells have receptors that recognize infections. Thirdly, the receptor is specific to a certain class of infections, that is, it is capable of recognizing not any foreign “structure,” but only a very specific one. But 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. Then, as happens in science, events developed progressively. Ruslan Medzhitov, who graduated from Tashkent University, then graduate school at Moscow State University, and later became a professor at Yale University (USA) and a rising star in world immunology, was the first to discover these receptors on human cells.

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

In fact, a conceptual revolution took place. It turned out that for everyone on Earth, innate immunity is the main one. And only the most “advanced” organisms on the ladder of evolution - higher vertebrates - acquire acquired immunity in addition. However, it is the innate that directs its initiation and subsequent operation, although many of the details of how all this is regulated have yet to be established.

"His Excellency's adjuvant"

New views on the interaction of the innate and acquired branches of immunity have helped to understand what was previously unclear.

How do vaccines work when they work? In general (and very simplified) form, it goes something like this. A weakened pathogen (usually a virus or bacteria) is injected into the blood of a donor animal, such as a horse, cow, rabbit, etc. The animal's immune system produces a protective response. If the protective response is associated with humoral factors - antibodies, then its material carriers can be purified and transferred into the human blood, simultaneously transferring the protective mechanism. In other cases, the person himself is infected or immunized with a weakened (or killed) pathogen, hoping to provoke an immune response that can protect against the real pathogen and even become entrenched in cellular memory for many years. This is how Edward Jenner, at the end of the 18th century, was the first in the history of medicine to vaccinate 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, many simple chemical compounds or proteins that are foreign to the body and would simply have to initiate a response from the immune system do not respond! And this often happens for the reason that the mechanism of the main defender - innate immunity - remains unawakened.

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

Freund's discovery was purely experimental and therefore may seem private. But Janeway sensed in it a moment of general significance. Moreover, he even called the inability to induce a full-fledged immune response to a foreign protein in experimental animals or in humans “the 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).

Janeway suggested that the innate immune system recognizes bacteria (both live and dead) by the components of their cell walls. Bacteria that live “on their own” need strong multilayer cell walls for external protection. Our cells, under a powerful cover of external protective tissues, do not need such shells. And bacterial membranes are synthesized with the help of enzymes that we do not have, and therefore the components of bacterial walls are precisely those chemical structures, ideal indicators of the threat of infection, for which the body, in the process of evolution, has produced recognition receptors.

A small digression in the context of the main topic.

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

It turned out that the walls of mycobacteria - namely, tuberculosis bacilli - are particularly 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, sending it a false signal that the body is infected with a dangerous pathogen. Force a reaction. But in fact, the vaccine does not contain such a pathogen at all or it is not so dangerous.

There is no doubt that it will be possible to find other, including non-natural, adjuvants for immunizations and vaccinations. This new direction of biological science is of enormous importance for medicine.

Turn on/off the desired gene

Modern technologies make it possible to turn off (“knockout”) the only gene in an experimental mouse that encodes one of the innate immune receptors. For example, responsible for recognizing the same gram-negative bacteria. Then the mouse loses the ability to provide its defense and, being infected, dies, although all other components of its immunity are not impaired. This is exactly how the work of immune systems at the molecular level is studied experimentally 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 with mutations in specific genes. For hundreds of years, examples have been known when in some families, clans and even tribes there was an extremely high mortality rate of children at an early age from very specific diseases. It now becomes clear that in some cases the cause is a mutation of some component of the innate immune system. The gene is turned off - partially or completely. Since most of our genes are in two copies, we must make special efforts to ensure that both copies are damaged. This can be “achieved” as a result of consanguineous 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 reason 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 immune 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 layer of protection, he will be able to cope with the threat and possibly live a full life. The danger will remain, but its level will decrease significantly. There is still hope that one day gene therapy will become part of everyday practice. Then the patient will simply need to transfer the “healthy” gene, without mutation. In mice, scientists can not only turn off a gene, but also turn it on. In humans it is much more difficult.

About the benefits of curdled milk

It is worth remembering one more foresight of I.I. Mechnikov. A hundred years ago, he connected the activity of phagocytes he discovered 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 digestion process. 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 innate immune receptors, bacteria send the body some “tonic” signals, 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 intestines, 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 (is it the last?) revolution in immunology is too short a period for the widespread 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 conducts development without taking into account new knowledge about the mechanisms of innate immunity. And some practical successes have already been achieved, 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. There is no need to doubt this. You just have to wait a little.

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

Sergey Arturovich Nedospasov - Head of the Department of Immunology, Faculty of Biology, Moscow State University. M. V. Lomonosova, head of the laboratory of the Institute of Molecular Biology named after. V. A. Engelhardt RAS, head of department of the Institute of Physical and Chemical Biology named after. 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 the revolution in immunology. - 2009, no.