The foundation of immunology was laid by the invention of the microscope, thanks to which it was possible to detect the first group of microorganisms - pathogenic bacteria.
At the end of the 18th century, English country doctor Edward Jenner reported the first successful attempt to prevent the disease through immunization. His approach grew out of observations of an interesting phenomenon: milkmaids often became infected with cowpox and subsequently did not suffer from smallpox. Jenner injected the little boy with pus taken from a cowpox pustule (abscess) and was convinced that the boy was immune to smallpox.
Jenner's work gave rise to the study of the germ theory of disease in the 19th century by Pasteur in France and Koch in Germany. They found antibacterial factors in the blood of animals immunized with microbial cells.
Louis Pasteur successfully grew various microbes in the laboratory. As often happens in science, the discovery was made by accident while cultivating chicken cholera pathogens. During work, one of the cups with microbes was forgotten on the laboratory table. It was summer. The microbes in the cup were heated several times by the sun's rays, dried out and lost their ability to cause disease. However, chickens that received these defective cells were protected against a fresh culture of cholera bacteria. Weakened bacteria not only did not cause disease, but, on the contrary, provided immunity.
In 1881 Louis Pasteur developed principles of vaccine creation from weakened microorganisms in order to prevent the development of infectious diseases.
In 1908, Ilya Ilyich Mechnikov and Paul Ehrlich were awarded the Nobel Prize for their work on the theory of immunity.
I. Mechnikov created the cellular (phagocytic) theory of immunity, according to which the decisive role in antibacterial immunity belongs to phagocytosis.
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 all foreign particles (including bacteria) that penetrate 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. I. I. Mechnikov realized that this phenomenon is not the nutrition of a given single cell, but a protective process in the interests of the whole organism. The scientist named the protective cells that act in this way phagocytes- "devouring cells". I. I. Mechnikov was the first to consider inflammation as a protective rather than a destructive phenomenon.
At the beginning of the 20th century, most pathologists opposed the theory of I.I. Mechnikov, since they considered leukocytes (pus) to be pathogenic cells, and phagocytes to be carriers of infection throughout the body. However, Mechnikov's work was supported by Louis Pasteur. He invited I. Mechnikov to work at his institute in Paris.
Paul Ehrlich discovered antibodies and created humoral theory of immunity, having established that antibodies are transferred to the baby through breast milk, creating passive immunity. Ehrlich developed a method for making diphtheria antitoxin, which saved millions of children's lives.
Ehrlich's theory of immunity says that there are special receptors on the surface of cells that recognize foreign substances ( antigen-specific receptors). When faced with foreign particles (antigens), these receptors are detached from the cells and released into the blood as free molecules. In his article, P. Ehrlich called antimicrobial substances in the blood the term " antibody", since bacteria at that time were called "microscopic bodies".
P. Ehrlich assumed that even before contact with a specific microbe, the body already has antibodies in the form that he called “side chains.” It is now known that he had in mind lymphocyte receptors for antigens.
In 1908, Paul Ehrlich was awarded the Nobel Prize for the humoral theory of immunity.
A little earlier, Karl Landsteiner first proved the existence of immunological differences between individuals within the same species.
Peter Medovar has proven the amazing accuracy of recognition of foreign proteins by immune cells: they are able to distinguish a foreign cell by just one changed nucleotide.
Frank Burnet postulated the position (Burnet's axiom) that the central biological mechanism of immunity is the recognition of self and foe.
In 1960, Peter Medawar and Frank Burnet received the Nobel Prize in Physiology or Medicine for their discovery immunological tolerance(lat. tolerance- patience) - recognition and specific tolerance to certain antigens.
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- III. Recommendations for completing assignments and preparing for seminar classes. To study the categorical apparatus, it is advisable to refer to the texts of the Federal Law indicated in the list of recommended literature
Immunity- this is a method of protection from living bodies and substances that carry signs of genetic foreignness. This is one of the clearest and most concise definitions of immunity, belonging to R.V. Petrov.
The term immunity (immunis) was used even before our era. Thus, in Ancient Rome, immunity was understood as exemption from paying taxes and performing duties.
The first experimental confirmation of protective mechanisms against infection was obtained by the English doctor E. Jenner, who carried out successful vaccination against smallpox. Subsequently, Louis Pasteur substantiated the theory of vaccination against infectious diseases. Since that time, immunity has come to be understood as immunity to infectious agents - bacteria and viruses.
The concept of immunity has expanded significantly thanks to the work of N. F. Gamaleya - it turned out that the body has protective mechanisms against tumors and genetically foreign cells. The discovery of I.I. became fundamental. Mechnikov phenomena of phagocytosis. He was the first to prove the possibility of the body rejecting its own old or damaged cells. The discovery of phagocytosis was the first explanation of the mechanism of destruction of pathogens by immune factors. Almost simultaneously with the discovery of cellular mechanisms, P. Ehrlich discovered humoral factors of immunity, called antibodies. The beginning of clinical immunology is associated with the name of O. Bruton, who described a clinical case of hereditary agammaglobulinemia. This was the first confirmation that a deficiency of immune factors can lead to the development of human diseases.
Having summarized the accumulated data, F. Vernet in the middle of the 20th century. substantiated the idea of immunity as a system that controls the constancy of the genetic composition of the body. However, according to modern concepts, immunity does not work at the level of the genotype, but with the phenotypic manifestations of hereditary information. F. Vernet proposed a clonal selection theory of immunity, according to which, based on a certain antigen in the immune system, selection (selection) of a specific lymphocyte occurs. The latter, through reproduction, creates a clone of immunocytes (a population of identical cells).
All over the world, the doctrine of immunity occupies a central place in the training of doctors of all specialties. This is due to the fact that the immune system, which guards antigenic homeostasis, is one of the most important adaptation systems of the body.
It is known that immune disorders naturally lead to aggravation of the course of the acute process, generalization, chronicity and recurrence of various diseases, which in turn is the cause of a number of pathological conditions. Unfavorable environmental conditions, stress, nutritional disorders, certain medications, surgical interventions and many other factors reduce the body's reactivity and its resistance to infectious agents.
Protective properties of the body
The first stage of the body’s self-defense is represented by the skin, mucous membranes of the nose, respiratory tract, and digestive organs.
The second stage of the body’s defense is represented by blood leukocytes (white blood cells).
The third stage of the body's defense against infectious diseases is the production of antibodies and antitoxins. Antibodies cause germs to stick together and dissolve. Antitoxins neutralize toxic substances produced by microbes by breaking them down. The ability of the human body to form antibodies and antitoxins and with their help to fight pathogenic microbes in order to protect itself is called immunity.
Spleen
It is located in the upper abdominal cavity, under the left rib. Its weight in an adult reaches 140-200 g.
The spleen produces lymphocytes that enter the lymphatic vessels. Lymphocytes have the ability to absorb and dissolve (phagocytose) microbes that enter the body. This means that the spleen is involved in protecting the body from infectious diseases (in immunity). In addition, excess blood accumulates in the spleen; in other words, the spleen is a “blood depot”. Along with this, the breakdown of worn-out blood cells (erythrocytes and leukocytes) occurs in the spleen.
When engaged in physical labor and sports, the formation of lymphocytes in the spleen increases. And at the same time, the body’s defenses (immunity) increase.
Types of immunity
Depending on the localization of the effect on the body, the following are distinguished:
- general immunity
- local immunity
Depending on the origin there are:
- innate immunity
- acquired immunity
According to the direction of action, they are distinguished:
- infectious immunity
- non-infectious immunity.
A separate group includes:
- humoral immunity
- cellular immunity
- phagocytic immunity.
General immunity
Local immunity
Innate immunity
Innate immunity is passed on to the child from the mother. But it is not permanent and already in the first year of a child’s life loses its strength.
Acquired immunity
Acquired, that is, developed by the body itself during its own life, immunity (antibodies and antitoxins), in turn, can be natural or artificial.
Active acquired immunity
Natural immunity is developed after a person has suffered certain infectious diseases. Artificial immunity is developed in the body of a healthy person after vaccinations. For vaccinations, vaccines are prepared in special laboratories from weakened pathogenic microbes and viruses.
Natural and artificial immunity are produced in the body itself, so they are combined under the general name active immunity.
Passive acquired immunity
In addition, there is also passive immunity. After vaccination, immunity is created in the body of some donors against the causative agents of certain diseases and their toxic substances.
The famous Russian scientist I.I. Mechnikov was the first in Russia to prepare and use a vaccine and blood serum to prevent rabies, anthrax and other diseases. Material from the site
Infectious immunity
Infectious immunity is divided into antimicrobial and antitoxic. Antimicrobial immunity in turn includes antibacterial, antiviral, antifungal and antiprotozoal.
Immunology as a specific area of research arose from the practical need to combat infectious diseases. Immunology emerged as a separate scientific field only in the second half of the twentieth century. The history of immunology as an applied branch of infectious pathology and microbiology is much longer. Centuries-long observations of infectious diseases laid the foundation for modern immunology: despite the widespread spread of the plague (5th century BC), no one fell ill twice, at least fatally, and those who had recovered were used to bury corpses.
There is evidence that the first smallpox vaccinations were carried out in China a thousand years before the birth of Christ. Inoculation of the contents of smallpox pustules into healthy people in order to protect them from the acute form of the disease then spread to India, Asia Minor, Europe, and the Caucasus.
Inoculation was replaced by the vaccination method (from the Latin “vacca” - cow), developed at the end of the 18th century. English doctor E. Jenner. He drew attention to the fact that milkmaids who cared for sick animals sometimes became ill with cowpox in an extremely mild form, but never suffered from smallpox. Such an observation gave the researcher a real opportunity to combat the disease in people. In 1796, 30 years after the start of his research, E. Jenner decided to try the cowpox vaccination method. The experiment was successful and since then the E. Jenner vaccination method has found wide use throughout the world.
The origin of infectious immunology is associated with the name of an outstanding French scientist Louis Pasteur. The first step towards a targeted search for vaccine preparations that create stable immunity to infection was made after Pasteur’s observation of the pathogenicity of the causative agent of chicken cholera. From this observation, Pasteur concluded: an aged culture, having lost its pathogenicity, remains capable of creating resistance to infection. This determined for many decades the principle of creating vaccine material - in one way or another (for each pathogen, its own) to achieve a reduction in the virulence of the pathogen while maintaining its immunogenic properties.
Although Pasteur developed the principles of vaccination and successfully applied them in practice, he was not aware of the factors involved in the process of protection against infection. The first to shed light on one of the mechanisms of immunity to infection were Emil von Behring And Kitazato. They demonstrated that serum from mice pre-immunized with tetanus toxin, injected into intact animals, protected the latter from a lethal dose of the toxin. The serum factor formed as a result of immunization - antitoxin - was the first specific antibody discovered. The work of these scientists laid the foundation for the study of the mechanisms of humoral immunity.
The Russian evolutionary biologist was at the origins of knowledge of the issues of cellular immunity Ilya Ilyich Mechnikov. In 1883, he made the first report on the phagocytic theory of immunity at a congress of doctors and natural scientists in Odessa. Humans have amoeboid motile cells - macrophages and neutrophils. They “eat” a special kind of food - pathogenic microbes, the function of these cells is to fight microbial aggression.
In parallel with Mechnikov, the German pharmacologist developed his theory of immune defense against infection Paul Ehrlich. 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.
Two theories - phagocytic (cellular) 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.
By the end of the 40s and the beginning of the 50s of the twentieth century, the first period of development of immunology was ending. An entire arsenal of vaccines has been created against a wide range of infectious diseases. Epidemics of plague, cholera, and smallpox no longer destroyed hundreds of thousands of people. Isolated, sporadic outbreaks of these diseases still occur, but these are only very local cases that do not have epidemiological, much less pandemic significance.
Rice. 1. Immunology scientists: E. Jenner, L. Pasteur, I.I. Mechnikov, P. Erlich.
A new stage in the development of immunology is associated primarily with the name of the outstanding Australian scientist M.F. Burnet. It was he who largely determined the face of modern immunology. Considering immunity as a reaction aimed at differentiating everything “one’s own” from everything “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 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. The formula of this theory is simple: one clone of lymphocytes is capable of responding only to one specific, antigenic, specific determinant.
Burnet’s views on immunity as a reaction of the body that distinguishes everything “our own” from everything “foreign” deserve special attention. After Medawar proved the immunological nature of rejection of a foreign transplant, after the accumulation of facts on the immunology of malignant neoplasms, it became obvious that the immune reaction develops not only to microbial antigens, but also when there are any, albeit minor, antigenic differences between the body and that biological material (transplant, malignant tumor) with which he meets.
Today we know, if not all, then many of the mechanisms of the immune response. We know the genetic basis of the surprisingly wide variety of antibodies and antigen recognition receptors. We know which cell types are responsible for the cellular and humoral forms of the immune response; the mechanisms of increased reactivity and tolerance are largely understood; much is known about antigen recognition processes; molecular participants in intercellular relationships (cytokines) were identified; In evolutionary immunology, the concept of the role of specific immunity in the progressive evolution of animals was formed. Immunology as an independent branch of science stands on a par with truly biological disciplines: molecular biology, genetics, cytology, physiology, evolutionary teaching.
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.
To explain the complex and often mysterious mechanisms and manifestations of immunity, scientists have put forward many hypotheses and theories. However, only a few of them have received fundamental confirmation or were justified theoretically, while most have only historical significance.
The first fundamentally important theory was the theory of side chains, put forward by P. Ehrlich (1898). According to this theory, cells of organs and tissues have receptors on their surface that, due to chemical affinity with the antigen, bind the latter. Instead of antigen-bound receptors, the cell produces new receptors. Their excess enters the blood and provides immunity to the antigen. This theory, although naive in its core, introduced into immunology the principle of the formation of antibodies capable of binding antigen, i.e. laid the foundations for the concept of humoral immunity.
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.
Also worthy of mention are the so-called instructive theories, which explain the mechanisms of formation of specific antibodies by the instructive action of antigens. According to these theories [Breinl F., Gaurowitz F., 1930; Pauling L., 1940] - matrix theories of antibody formation, antibodies are formed in the presence of an antigen - the antigen is like a matrix on which the antibody molecule is stamped.
A number of theories [Erne N., 1955; Vernet F., 1959] proceeded from the assumption of the pre-existence of antibodies in the body to almost all possible antigens. This theory was substantiated especially deeply and comprehensively by F. Vernet in the 60-70s of our century. This theory is called clonal selection and is one of the most substantiated theories in immunology.
According to F. Burnet's theory, lymphoid tissue consists of a huge number of clones of cells specialized in the production of antibodies to various antigens. Clones arose as a result of mutations and cloning under the influence of antigens. Therefore, according to the theory, clones of cells pre-exist in the body that are capable of producing antibodies to any antigens. An antigen that enters the body causes activation of “its” clone of lymphocytes, which selectively multiplies and begins to produce specific antibodies. If the dose of the antigen affecting the body is large, then the clone of “its” lymphoid cells is eliminated, eliminated from the general population, and then the body loses the ability to respond to its antigen, i.e. he becomes tolerant of him. Thus, according to F. Burnet, tolerance to one’s own antigens is formed in the embryonic period. F. Burnet's theory explains many immunological reactions (antibody formation, antibody heterogeneity, tolerance, immunological memory), but does not explain the pre-existence of lymphocyte clones capable of responding to a variety of antigens. According to F. Burnet, there are about 10,000 such clones. However, the world of antigens is much larger and the body is capable of responding to any of them. The theory does not answer these questions. The American scientist S. Tonegawa brought some clarity to this idea, who in 1988 substantiated from a genetic point of view the possibility of the formation of specific immunoglobulins for almost all conceivable antigens. This theory is based on the fact that genes are shuffled in humans and animals, resulting in the formation of millions of new genes. This process is accompanied by an intense mutation process. From here, from the V- and C-genes, the genes of the H- and L-chains, a huge number of genes encoding immunoglobulins of various specificities can arise, i.e. practically specific to any antigen.
Mention should also be made of the theory of regulatory networks (immune network), the main core idea of which is idiotype-anti-idiotypic regulation put forward by the American scientist N. Erne in 1974. According to this theory, the immune system is a chain of interacting idiotypes and anti-idiotypes, i.e., specific structures of the active center of antibodies formed under the influence of an antigen. The introduction of an antigen causes a cascade chain reaction of the formation of antibodies 1st, 2nd, 3rd, etc. orders of magnitude. In this cascade, a 1st order antibody causes the formation of a 2nd order antibody, the latter causes the formation of a 3rd order antibody, etc. In this case, the antibody of each order carries an “internal image” of the antigen, which is relayed in the chain of formation of anti-idiotypic antibodies.
Evidence for this theory is the existence of anti-idiotypic antibodies that carry the “image” of the antigen and are capable of inducing immunity to this antigen, as well as the existence of T-lymphocytes sensitized to anti-idiotypic antibodies that carry receptors for these antibodies on their surface.
Using N. Erne's theory, it is possible to explain the formation of “immunological memory” and the occurrence of autoimmune reactions. However, this theory does not explain many phenomena of immunity, for example, how the body distinguishes “self” from “foreign”, why passive immunity does not turn into active, when and why the cascade of anti-idiotypic reactions subsides, etc.
In the 60s, the outstanding Soviet immunologist P.F. Zdrodovsky formulated the physiological concept of immunogenesis - the hypothalamic-pituitary-adrenal theory of immune regulation. The main idea of the theory was that hormones and the nervous system play a regulatory role in the formation of antibodies, and the production of antibodies is subject to general physiological laws. However, the theory does not address the cellular and molecular mechanisms of immunogenesis.
