The Great Immunological Revolution. Ilya Mechnikov - creator of the cellular theory of immunity What the discovery of immunity gave humanity

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

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

Paul Ehrlich

A prominent representative of the German school of microbiologists was Paul Ehrlich (1854-1915). Since 1891, Ehrlich has been searching for chemical compounds capable of suppressing the life activity of pathogens. He introduced the treatment of four-day malaria with methylene blue dye and the treatment of syphilis with arsenic.

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

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

Bering was engaged in the creation of serums by selecting bacterial cultures and toxins, which he injected into animals. One of his greatest achievements is the creation in 1890 of antitetanus serum, which turned out to be very effective in the prevention of tetanus in wounds, although ineffective in a later period, when the disease had already developed.

“Behring wanted the honor of discovering the anti-diphtheria serum to belong to German, not French, scientists. In search of vaccinations for diphtheria-infected animals, Bering made serums from various substances, but the animals died. He once used iodine trichloride for vaccination. True, this time the guinea pigs became seriously ill, but none of them died. Inspired by the first success, Bering, after waiting for the experimental pigs to recover, inoculated them from a broth with diphtheria toxin strained using the Roux method, in which diphtheria bacilli had previously been grown. The animals withstood the vaccination perfectly, despite the fact that they received a huge dose of the toxin. This means that they have acquired immunity against diphtheria; they are not afraid of either bacteria or the poison they secrete. Bering decided to improve his method. He mixed the blood of recovered guinea pigs with a strained liquid containing diphtheria toxin and injected the mixture into healthy guinea pigs - none of them got sick. This means, Bering decided, the blood serum of animals that have acquired immunity contains an antidote to diphtheria poison, some kind of “antitoxin”.

By inoculating healthy animals with serum obtained from recovered animals, Bering became convinced that guinea pigs gained immunity not only when infected with bacteria, but also when they were exposed to a toxin. Later he became convinced that this serum also had a healing effect, that is, if sick animals were vaccinated, they would recover. At the clinic for children's diseases in Berlin, on December 26, 1891, a child dying of diphtheria was inoculated with the serum of a recovered mumps, and the child recovered. Emil Bering and his boss, Robert Koch, won a triumphant victory over the terrible disease. Now Emil Roux has taken up the matter again. By inoculating horses with diphtheria toxin at short intervals, he gradually achieved complete immunization of the animals. Then he took several liters of blood from horses, extracted serum from it, from which he began to vaccinate sick children. Already the first results exceeded all expectations: the mortality rate, which previously reached 60 to 70% for diphtheria, fell to 1–2%.

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

Good afternoon, dear friends! So, today we will again talk about an important component for human health - his immunity.

Of course, we all understand that it is necessary to monitor our health, and each of us has repeatedly heard and uttered this phrase ourselves - increasing immunity. Today our topic will be one of the sides of this issue, namely, what is humoral immunity?

This term is especially often heard in medical institutions. Let's try and understand what this means and how it works. The classification of the types of human defense system is quite extensive and includes several points.

Humoral factors of immunity, in simple terms, are the constant production of antibodies designed to destroy pathogenic viruses and infectious manifestations. Confrontation must be constant; this is the only way to maintain health and prevent dangerous diseases. Human immunity is a link that should not be weak.

In connection with this type of protective system, it is impossible not to mention the second type, which is somewhat different in its functionality, but is inextricably linked with the above. This is a cellular type of defense system. Together they allow you to achieve an excellent effect. What are the differences between cellular and humoral immune protection?

Cellular has the ability to recognize and infect fungi, viruses, foreign cells and tissues in its own cellular structures.
The humoral theory of immunity is associated with the defeat of bacteria located in the pericellular space, and mainly in the plasma.

The theory is based on the processes of specific interaction of antibodies. The basis of immunity B - lymphocytes, synthesized with native proteins, are able to instantly respond to the appearance of foreign proteins.

Moreover, as soon as a foreign substance appears in the blood, even regardless of its harmfulness, antibodies are immediately formed. And such a reaction can cause the defeat of the “foreigner” without much effort.

That is, to make it completely clear, the mechanism of action is simple, the protection of our blood and cells during humoral immunity is carried out by antigen proteins. They are included in the blood and other fluids of our body.

Humoral immunity - this is the recognition of bacteria in any body fluid, be it blood, lymph, saliva or others. The name “humoral” means liquid, moisture. With the widespread formation of antibodies or immunoglobulins, be it in the bone marrow, lymph nodes or intestines, protein compounds “stick” to foreign bacterial structures. They are successfully destroyed, then removed from the body with the same liquid. There are five main types of immunoglobulins:

A, D, E, G, M. Of all the lymphocytes in us, about 15% of them are detected in the body.

A little history

The history of the study of the humoral component of immunity goes back to the years when, in the 19th century, a dispute arose between two outstanding scientists Ilya Mechnikov and Paul Ehrlich. At that time, so much attention was not paid to the issue of immunity and people suffered from constant serious illnesses and infectious lesions.

On the basis of this intractable problem, the opinions of learned men came together in a dispute. Mechnikov's evidence was based on the fact that the immune properties of the human body work exclusively at the level of cellular processes. That is, cells are the basis of immunity.

Ehrlich argued with his opponent and argued that blood plasma is the main engine of protective processes, and immunity depends on its composition. This went on for many years, and none of them became the winner of the important dispute, or rather, they both turned out to be winners and received a Nobel Prize.

Here is a true story from the life of great scientists, which made it possible through long research to make an important discovery. It is believed that humoral immunity was discovered by P. Ehrlich.

It turned out that one proved the advantages of cellular immunity, and the other humoral. We know the outcome of the dispute; both protective systems are of great importance for humans and are closely interrelated with each other. The regulation of protective processes occurs in two systems, cellular and molecular.

Only through the interaction of this symbiosis did a multicellular creature emerge that can withstand the endless attacks of viruses and pathogenic microbes. And the name of this creature is Man. Our unique system has allowed us to survive and survive through millennia, constantly adapting to our environment.

Humoral specific and nonspecific immunity

We all react differently to external negative factors that can cause disease. Some begin to mope and experience signs of illness from the slightest breath of wind, others can withstand an icy hole. All this is the mechanism of action of the protective background.

Today, doctors classify the work of the human body as specific and nonspecific. Let's take a closer look at each of the concepts.

A specific reaction or form is directed to any single factor. An example would be a person who had chickenpox as a child, after which he developed a strong immunity to this disease. This can also include all those vaccinations and immunizations that we received in childhood.
The nonspecific form implies universal protection given by nature and the body’s reaction to the penetration of infection into the body.

Let's look at the principle of operation of these two forms in more detail.

Factors with specific properties primarily include immunoglobulins or antibodies. They are carried out by white cells in the blood, otherwise they can be called B lymphocytes. How are antibodies produced in the body?

The first part always appears by transmission at birth from the mother, the second through breast milk. Time passes, and a person becomes able to produce them himself from stem cells or after exposure to a vaccine.

Nonspecific factors include substances without a clear specialization, these are: tissue particles of the body, blood serum and proteins in it, glands and their secretory ability to suppress the growth of microbes, lysozyme, which contains an antibacterial enzyme.

The humoral component of immunity plays an important role in both cases and is built by the constant formation of “smart” antibodies in the internal systems of the body.

Violations

Study methods make it possible to identify disorders in humoral immunity. This is done using a special analysis - an immunogram. This examination allows you to understand the number of B lymphocytes, immunoglobulins, interferon levels and other important parameters in the body.

This test is performed by drawing blood from a vein. This is done on an empty stomach in the morning, so that before that there is 8 hours of abstinence from food, alcohol and smoking.

All these are quite difficult concepts for the average person to understand; rather, this is the prerogative of specialists. But still, it is interesting to understand the principle of immunity and expand your horizons a little on this issue. Don’t forget to support your body, and remember, your health depends on the state of humoral immunity!

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.

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.

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.

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

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

Natural and acquired immunity

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

The second appears in a person only after he has suffered from the disease. For example, typhus and scarlet fever are the first infections to which doctors discovered resistance. During the disease process, the body creates antibodies that protect it from certain germs and viruses.

The great importance of immunity is that after recovery the body is ready to face re-infection. This is facilitated by:

maintaining the antibody pattern for life;
recognition by the body of a “familiar” disease and rapid organization of defense.

There is a softer way to acquire immunity - a vaccination. There is no need to fully experience the disease. It is enough to introduce a weakened disease into the blood to “teach” the body to fight it. If you want to know what the discovery of immunity gave to humanity, you should first know the chronology of discoveries.

A little history

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

Preparations made from the blood of such animals became known as serums. They became the first cure for diseases, which gave humanity the discovery of immunity.

Serum as a last chance

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

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

The most important thing that the discovery of immunity gave humanity was an understanding of the functioning of the body as a whole. Scientists have finally understood how antibodies appear and what they are needed for.

Antibodies - fighters against dangerous toxins

Antitoxin began to be called a substance that neutralizes the waste products of bacteria. It appeared in the blood only if these dangerous compounds were ingested. Then all such substances began to be called a general term - “antibodies”.

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

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

The Importance of Opening Immunity

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

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

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

The term "immunity" comes from the Latin word "immunitas" - liberation, getting rid of something. It entered medical practice in the 19th century, when it began to mean “freedom from illness” (French Dictionary of Litte, 1869). But long before the term appeared, doctors had a concept of immunity in the sense of a person’s immunity to disease, which was designated as “the self-healing power of the body” (Hippocrates), “vital force” (Galen) or “healing force” (Paracelsus). Doctors have long been aware of the natural immunity (resistance) inherent in humans to animal diseases (for example, chicken cholera, canine distemper). This is now called innate (natural) immunity. Since ancient times, doctors have known that a person does not get sick from some diseases twice. So, back in the 4th century BC. Thucydides, describing the plague in Athens, noted the facts when people who miraculously survived could care for the sick without the risk of getting sick again. Life experience has shown that people can develop persistent immunity to re-infection after suffering severe infections, such as typhoid, smallpox, scarlet fever. This phenomenon is called acquired immunity.

At the end of the 18th century, Englishman Edward Jenner used cowpox to protect humans from smallpox. Convinced that artificially infecting humans was a harmless way to prevent serious illness, he conducted the first successful experiment on humans in 1796.

In China and India, smallpox vaccination was practiced several centuries before its introduction in Europe. The sores of a person who had had smallpox were used to scratch the skin of a healthy person, who usually then suffered the infection in a mild, non-fatal form, after which he recovered and remained resistant to subsequent smallpox infections.

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

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

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

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

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

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