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The history of the development of immunology as a science

Description of the epidemics appeared a long time ago, the first of them are 2000 BC. in the Babylonian epic of Galmash.

In those distant times, the nature of various epidemics and the relationship between them remained a mystery, but attentive eyewitnesses could not help but notice that a new wave of the disease often spares those who have suffered this disease before. The ancient Greek historian Thucydides, describing the plague epidemic in Athens in 430 BC, notes that people who have been ill and survived are never infected again. Another historian of the time of Emperor Justinian, Procopius, writes: "Then she (the plague) returned, and those inhabitants of this land who had previously been particularly hard hit, she did not touch at all." Over time, resistance to re-infection began to be called the word “immunity” - from the Latin immunitas (which, incidentally, originally meant the release of a citizen from some state duty or service).

The notion of illness as a punishment contained a hidden theory of immunity. If the disease is punishment for sin, then to be unaffected by it at the height of the epidemic (that is, to have natural immunity) was automatically perceived as evidence of a godly life. In the time of early Christianity, these ideas have changed markedly. Now the disease is redemption and purification, and a person who has recovered and atoned for his sins is not subject to new punishment when the plague (illness) repeats (acquired immunity).

In the X century, the Persian physician Razes described the signs of the difference between smallpox and measles and other febrile diseases with a rash, noting that smallpox affects mainly children, much less often adults and old people; that the survivors remain lifelong immunity to this disease. The involvement of Razes in immunology was manifested in the methods of treatment. So for some reason he suggested treating people bitten by poisonous scorpions with donkey serum bitten by the same scorpions.

Avicenna in the XI century put forward the theory of acquired immunity. The Italian doctor Girolamo Fracastoro developed and described it in the book “Contagion” (1546). Avicenna and Fracastoro believed that all diseases are caused by small “seeds” (seeds, germs, semi-naria). “Infection seeds” are transferred from person to person, have “different affinities for different plants and animals, and inside the body - for different organs and fluids

Smallpox vaccinations

According to legend, the practice of preventing smallpox disease existed in ancient China. There they did it this way: healthy children were injected into the nose through a silver tube with powder obtained from crushed dry crusts (scabs) from smallpox sores of people with smallpox, and the boys were blown through the left nostril, and the girls through the right. A similar practice has taken place in traditional medicine in many countries of Asia and Africa. Since the beginning of the XVIII century, the practice of anti-vaccine vaccines came to Europe. This procedure was called “variolation” (from lat. Variola - smallpox).

According to the surviving documents, in Constantinople they began to plant smallpox in 1701. Vaccinations did not always end well, but in the event of an epidemic, mortality was 15–20 percent. Sick pox remained with ugly dents on the skin, including on the face. Therefore, supporters of vaccinations persuaded people to decide on them at least for the beauty of their daughters' faces (as, for example, Voltaire in the Philosophical Notebooks and Jean-Jacques Rousseau in the novel New Eloise). Montage brought the idea and material for smallpox vaccination from Constantinople to England. She made a variation to her son and daughter and persuaded the Princess of Wales to instill the children. But before risking children from the royal family, six prisoners were vaccinated, promising them release if they tolerate variation well. The prisoners did not fall ill, and in 1722 the prince and princess of Wales instilled smallpox into their two daughters, which set a monarchy example for the inhabitants of England.

In 1746, a special hospital of Saint Pancras was opened in London, in which smallpox was vaccinated. Since 1756, the practice of variolation, also voluntary, took place in Russia. But the practice of quarantines in the territories covered by then-known infectious diseases of people and farm animals in Russia has existed for several centuries, and by no means voluntary, but rather harsh. And this expressed the state’s concern for the health of the uninfected population and the country as a whole.

XVIII - XIX centuries. The beginning of the history of modern immunology. Vaccination. Vaccinations against rabies, anthrax, chicken cholera.

In the XVII - XVIII centuries, the history of modern immunology begins to track with the work of the English physician Edward Jenner. In 1798, an article appeared where he described his trials of vaccinating smallpox vaccines: first to one 8-year-old boy and then to another 23 individuals. Six weeks after vaccination, Jenner risked vaccinating subjects with natural human smallpox - people did not get sick. He professionally noticed a similar practice with English farmers. The documents left the name of the farmer Benjamin Jesti, who in 1774 tried to scratch the contents of the pustules of cows sick with smallpox, his wife and child, with a knitting needle. It was based on the experience of peasants, indicating that human contact with cows with vaccinia (vaccinia) somehow protects against smallpox (smallpox). Jenner developed a medical technique for vaccination, which he called vaccination (vaccus - a cow in Latin). The term "survived" to the present day: vaccination is any artificial immunization in order to protect against disease.

In 1870-1890, thanks to the development of microscopy and methods of cultivating microorganisms, Louis Pasteur, Robert Koch, other researchers and doctors (A. Neisser, F. Leffler, G. Hansen, E. Klebs, T. Escherich, etc.) identified pathogens of more than 35 contagious diseases. The names of the discoverers remained in the names of the microbes - Neisseria, Leffler's wand, Klebsiella, Escherichia, etc. Since that time, the development of immunology has been associated with medical bacteriology. R. Koch identified the causative agents of tuberculosis and cholera and worked a lot with the causative agent of anthrax (Bacillus anthracis). He described the tuberculin reaction, that is, the phenomenon of delayed-type skin hypersensitivity, and experimentally showed the specificity of immunization, formulated criteria for the diagnosis of infectious diseases, known as Koch postulates.

In science, the method "decides everything." R. Koch was the first to develop methods for isolating pure bacterial cultures on solid nutrient media (cloning of microorganisms), the first to use aniline dyes for staining microbes, and to improve the technique of microcopying by immersion of the microscope objective. He owns the first micrographs of bacteria under a microscope.

L. Pasteur went down in history as the creator of vaccines against chicken cholera, anthrax, rabies and as the author of the method of attenuation of microorganisms - weakening the infectiousness of microbes by artificial treatments in the laboratory. According to legend, L. Pasteur discovered the attenuation by chance.

He (or laboratory assistant) forgot a test tube with a culture of cholera vibrio in a thermostat, the culture overheated. Nevertheless, experimental chickens were introduced to her, but they did not become ill with cholera. Experienced chickens were not thrown out for reasons of resource saving, but after some time they were again used in experiments on infection, but not with a spoiled, but with a fresh culture of cholera vibrio. However, these hens did not get sick again. L. Pasteur drew attention to this and confirmed in other experiments (his successful public experience in vaccinating 27 sheep with an anthrax vaccine in May 1881 is known) that the preliminary introduction of weakened (attenuated) microbes into the body can protect against the development of the disease in the future when infected with the same name but a virulent microbe.

Emil Rocks and L.
Pasteur showed that different strains of the same microorganism exhibit different pathogenicity, that is, cause clinical symptoms of varying severity. They developed methods for attenuating microorganisms and prepared attenuated vaccine strains of chicken cholera, rabies, and anthrax pathogens. L. Pasteur tested the rabies vaccine on a boy who was bitten by a sick dog. The boy did not get sick, which was regarded as an outstanding success. In Europe, and most of all in Russia (in Odessa, I.I. Mechnikov), they began to open the so-called Pasteur stations, where people bitten by animals were vaccinated against rabies.

In the history of immunology of the last 120 years, there are three changes of concepts in time:

I. At the end of the 19th and beginning of the 20th centuries, immunology grew out of medical bacteriology, in the first place, serology and its clinical applications developed. At this time (and to this day), immunology is also associated with pathological physiology in studies of allergic reactions, anaphylaxis and inflammation in any of its manifestations.

II. Since the First World War, chemical ideas are gaining momentum in immunology, and immunochemistry prevails methodically and theoretically until the mid 60s of the 20th century.

III. From the 60s of the XX century to the present, immunology is increasingly turning into a systemic discipline - immunobiology. The ideas and methods of immunology penetrated into all, without exception, including the most private, medical specialties. Today, in terms of the volume of acquired knowledge, immunology is recognized as the most developed field of biology and medicine among all other sections of the science of living.

In the first half of the 20th century, it was possible to create more or less effective vaccines against smallpox, chicken cholera, anthrax, rabies and plague. But the list of infections against which it is not possible to create effective vaccines (tuberculosis, leprosy, cholera, syphilis, most viral and parasitic infections) is constantly growing.

Vaccine “victories” have become more modest and are given with great difficulty. Max Tailer received the Nobel Prize in 1951 for a protective vaccine against yellow fever virus. Passive serotherapy has been limited to diphtheria and tetanus (using equine antisera) and is now a thing of the past. Now only passive serotherapy of the Rh conflict of the mother and the fetus, as well as antisera against potent poisons, has clinical use. Niels Jerne, one of the five (if not three) of the great immunologists of our time. In 1955, he formulated the first theory of biological selection in relation to immunity, which he called “natural selection”. Clonality of lymphocytes is the main theorem of immunology to this day.

But besides this, N. Jerne predicted that ligand recognition by lymphocyte receptors is hereditarily associated with the main histocompatibility complex. Until recently, the number of antibody-forming cells was calculated according to the method of N. Jerne.

His name is associated with the hypothesis of an immunological network - an idiotype - anti-idiotypic interactions of antibodies with anti-antibodies (1974). In recent years, this idea is rarely recalled, although it was for the theory of the immunological network that N. Jerne was awarded the Nobel Prize. We do not exclude that the idea of ​​the immunological network will be activated again, already on new factual material, when trying to understand the phenomena of lymphocyte tolerance in the process of constant immune responses and many other unsolved riddles of immunity that are not yet sufficiently explained.

The concept, “clonal selection theory of immunity,” belongs to F. Burnet, he propagandized and developed this theory, but in questions of authorship he himself referred to N. Jerne.

In 1945, Ray Owen described dizygotic twin calves that did not tear off transplants from each other, linking this to their embryonic parabiosis. It followed that the ability to develop an immune response to specific antigens arises in the embryonic period of ontogenesis and depends on the presence of these specific antigens in the internal environment. The existence of immunological tolerance, experimentally confirmed by Peter Medawar. He developed a model for the artificial induction of immunological tolerance by injecting newborn mice with hematopoietic cells from an allogeneic donor. In the works of the 40s, the scientist “rediscovered” the laws of transplantation and showed that transplant rejection is an immunological phenomenon, and antibodies are not an instrument of rejection.

F. Burnett, combining the thoughts and finds of several scientists, formulated the “theory of clone selection”:

1) natural antibodies are presented as receptors on the surface of some mesenchymal cells;

2) antigens, when ingested, bind these receptors;

3) there is a proliferation of a clone of cells whose receptors are associated with an antigen;

4) part of the clone cells becomes memory cells;

5) immunological tolerance is the result of a “clonal abortion” that occurs during certain critical periods of embryonic development.

F. Burnett and P. Medawar were awarded the Nobel Prize for the discovery and study of the phenomenon of induced immunological tolerance and for the understanding that tolerance is a property of the cells of the immune system that naturally develops during embryogenesis. The experiments of David Talmadge and Joshua Lederberg in the 60s of the XX century supported the cellular selective theory of immunity. D. Talmadj came to the conclusion (which modern immunologists have confirmed only in works in 2000 and not everyone accepts it so far) that a limited number of antibodies (clonotypes, in the terminology of the author) can bind a much larger variety of different antigens. Lederberg focused on genetics and came up with the idea that antibody diversity is determined by the high rate of somatic mutations in the “immunoglobulin gene” (this is actually a prediction of somatic recombination of DNA of immunoglobulin genes).

Developing a cellular clonal theory, F. Burnet believed: all that is needed to start an immune response is that the mesenchymal cells (as it later became known, lymphocytes) of a particular clone bind their antigen (single signal - the only signal). F. Burnett's authority was so high, and his ideas are so simple that for many years this idea has become generally accepted. But reality was again not so simple. The farther, the more facts accumulated, showing that a lymphocyte, in order to start an immune response, must necessarily receive other signals from its external environment, except for antigen binding. They predicted the two-signal model and then worked along with other researchers in its actual proof in 1969 by P. Bretcher and M. Cohn, a little later R. Langman joined them. They own the term T-helper lymphocytes for antibody-producing B-lymphocytes. In 1972, K. Lafferty and A. Cunningham showed that the activation of T-lymphocytes themselves requires two (from the point of view of that time) signals: 1) an antigen and 2) an obligatory co-stimulatory signal.
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