Natural history of immunity. Let's learn about everything that the discovery of immunity gave to humanity. What the discovery of immunity gave to humanity.
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.
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!
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 formation). 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.
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.
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.
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 with 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.
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.
