The discovery of pathogens was accompanied by the study of their biological properties, development of nomenclature and their classification. This stage in the development of microbiology can be called physiological. During this period, the processes and characteristics of metabolism in bacteria were studied: respiration, the need for organic and minerals, enzymatic activity, reproduction and growth, cultivation on artificial nutrient media etc.
The discoveries of the brilliant French scientist Louis Pasteur (1822-1895) were of great importance for the development of microbiology during this period. He not only substantiated the etiological role of microbes in the occurrence of diseases, but also discovered the enzymatic nature of fermentation - anaerobiosis (i.e. breathing in the absence of oxygen), refuted the position of spontaneous generation of bacteria, substantiated the processes of disinfection and sterilization, and also discovered and substantiated by example rabies and other infections vaccination principles, i.e. protective vaccinations against microbes.
Immunological period
microbiology virology immunological medicine
The fourth, immunological period in the development of microbiology begins with L. Pasteur. The scientist, in brilliant experiments on animals, using chicken cholera, anthrax and rabies as a model, developed the principles of creating specific immunity to microbes by vaccinating with weakened and also killed microbes. He developed a method of attenuation, i.e. weakening (reduction) of the virulence of microbes through repeated passages through the body of animals, as well as by growing them on artificial nutrient media in unfavorable conditions. The introduction of strains with reduced virulence to animals subsequently provided protection against diseases caused by virulent microbes. The effectiveness of vaccination with attenuated strains of microbes was brilliantly confirmed by L. Pasteur when saving people infected with the rabies virus.
Before L. Pasteur, the possibility of protective vaccinations against smallpox of people was known by applying the contents of pustules (pox) taken from cows with cowpox to the skin. This was first accomplished by the English physician E. Jenner (1749-1823) more than 200 years ago. Humanity celebrates this event with gratitude. Thus, 1996, which marked the 200th anniversary of smallpox vaccination, was declared the year of Jenner throughout the world. However, vaccinations against human smallpox with material containing the causative agent of cowpox were purely empirical in nature and did not lead to the development of general scientific principles of vaccine prevention. This was done by L. Pasteur, who had great respect for E. Jenner and, in his honor, proposed calling the drugs used for vaccinations vaccines (from the French vaca - cow).
L. Pasteur developed not only the principle of vaccination, but also a method of preparing vaccines, which has not lost its relevance today. Consequently, L. Pasteur is the founder of not only microbiology and immunology, but also immunobiotechnology.?
Development of immunology at the end of the 19th and beginning of the 20th centuries. associated with the names of two outstanding scientists - the Russian zoologist I.I. Mechnikov (1845--1916) and the German chemist P. Ehrlich (1854--1915). Both of these scientists, as well as Pasteur, are the founders of immunology. I.I. Mechnikov, who graduated from Kharkov University and became a professor at the age of 26, worked next to L. Pasteur for more than 28 years, being deputy for science at the Paris Pasteur Institute, headed by L. Pasteur himself. This institute was created in 1888 with donations from both ordinary people, and governments of various countries. The Russian Emperor made the most generous donation Alexander III. The Pasteur Institute is still one of the leading institutions in the world today. It is no coincidence that it was at this institute in 1983 that L. Montagnier discovered the human immunodeficiency virus.
I.I. Mechnikov developed the phagocytic theory of immunity, i.e. laid the foundations of cellular immunology, for which he was awarded the Nobel Prize. At the same time, the same prize was awarded to P. Ehrlich for the development of the humoral theory of immunity, which explained the mechanisms of protection with the help of antibodies. The humoral theory of P. Ehrlich was confirmed by the works of E. Bering and S. Kitazato, who first prepared antitoxic diphtheria serums by immunizing horses with diphtheria toxin.
Along with the development of vaccines and serums, the search for chemical antibacterial drugs that have bacteriostatic and bactericidal effects developed. The founder of this direction was P. Ehrlich, who was looking for a “magic bullet” against microbes. He was the first to create the drug "Salvarsan" (drug 606), which has a detrimental effect on spirochetes - the causative agent of syphilis. This area of chemotherapy and chemoprophylaxis is intensively developing and currently has many achievements, the culmination of which is the creation of antibiotics discovered by the English doctor A. Fleming.
The immunological period of development of microbiology laid a solid foundation for the isolation as independent discipline immunology, and also enriched microbiology with new immunological research methods, which made it possible to raise microbiology to a higher scientific and practical level. This was also facilitated by advances in the field of biochemistry, molecular biology, genetics, and subsequently genetic engineering and biotechnology. Since the 40-50s of the XX century. microbiology and immunology have entered the 5th molecular genetic stage of development. This stage is characterized by the flowering of molecular biology, which discovered the universality of the genetic code of humans, animals, plants and bacteria; molecular mechanisms of biological processes. Were deciphered chemical structures biologically vital active substances, such as hormones, enzymes, etc.; chemical synthesis of biologically active substances was carried out. Individual genes were deciphered, cloned and synthesized, recombinant DNA was created; Genetic engineering methods for obtaining complex biologically active substances are being introduced into practice, etc.
Immunology as a specific area of research arose from the practical need to combat infectious diseases. As a separate scientific direction immunology emerged 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 healthy people in order to protect them from the acute form of the disease, it then spread to India, Asia Minor, Europe, and the Caucasus.
Inoculation was replaced by the vaccination method (from the Latin “vacca” - cow), developed in late XVIII V. 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. Similar observation gave the researcher a real opportunity to combat human disease. 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 in the blood serum of animals infected with bacteria, protein substances, capable of killing 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.
Special attention Burnet's views on immunity as such a reaction of the body that distinguishes everything “our own” from everything “foreign” deserve. 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.
An English doctor stood at the origins of immunology Jenner, who developed a method of vaccination against smallpox. However, his research was private and concerned only one disease.
The development of scientific immunology is associated with the name Louis Pasteur, who took the first step towards a targeted search for vaccine preparations that create stable immunity to infections: he obtained and put into practice vaccines against cholera, anthrax, rabies obtained from microbes with weakened virulence (attenuated).
The founder of the doctrine of cellular immunity is I.I.Mechnikov, who created the phagocytic theory (1901-1908).
Bering and Ehrlich- laid the foundation for humoral immunity.
Emil von Behring– 1 laureate Nobel Prize in medicine (1901), awarded for the discovery of antitoxic antibodies and the development of antitetanus and antidiphtheria serums.
Ehrlich– founder of the theory of side chains (antibodies in the form of receptors are located on the surface of cells, antigen specifically selects the corresponding antibody receptors, ensures their release into the circulation and compensatory hyperproduction of antibodies (receptors).
The doctrine of antigens - K. Landsteiner, J. Bordet, who proved that ag can be not only microbes and viruses, but any animal cells. K. Landsteiner discovery of blood groups. (1930).
Ch. Richet– discovery of anaphylaxis and allergies (1913).
Burnet and Meadmaker(1960) - the doctrine of immunological tolerance, showed that the same mechanisms underlie the rejection of genetically foreign tissues and infectious immunity. M. Burnet, creator of the clonal selection theory of immunity - one clone of lymphocytes is capable of responding to only one specific antigenic determinant. And besides, Burnet is the author of one of the most important principles of immunology - the concept of immunological surveillance of the constancy of the internal environment of the body.
In the 60s, the doctrine of the T- and B immune systems began to develop rapidly ( Claman, Davis, Royt).
A theory of 3-cell cooperation of immunocytes in the immune response was proposed ( Petrov, Royt and etc.). The main participants in the proposed scheme were T and B lymphocytes and macrophages.
· deciphering the structure of Ig - ( Porter, Eidelman)
· discovery of structures encoded by MHC – ( Benaceraf, Snell)
· gene control of the immune response, antibody diversity and the importance of some genes in susceptibility to diseases
· production of monoclonal antibodies and substantiation of network regulation of immunogenesis ( Koehler, Milstein, Jerne)
Currently, there is an intensive development of clinical immunology and a widespread introduction into practical medicine of the achievements of theoretical immunology (deciphering the pathogenesis of many diseases; creating new classifications; classification of diseases of the immune system; development of immunodiagnostic methods (ELISA, RIA, polymerase chain reaction, etc.), immunotherapy) .
The main stages of the formation and development of immunology:
1796 – 1900– infectious immunology
1900 – 1950- normal immunology
1950 to present– modern stage
Molecular biological methods and technologies became an integral part of immunology at the turn of the 80s and 90s, which marked its transition to a new level. At this time, the use of genetic approaches in research became an important indicator of data reliability. Transfection and gene knockout, as well as the use of cell clones and monoclonal antibodies, have become extremely widely used. This period is characterized by active appeal (at new methodological and ideological levels) to infectious immunology, including the creation of new types of vaccines. At the same time, interest in the practical application of the results obtained intensified (perhaps this was a consequence of the extreme rise in cost of scientific research, the conduct of which needed to be given a practical justification). Immuno-oncology has become a favorite area for the creation and application of new molecular biological models. The concept of “vaccine” has undergone changes: now this term has come to mean not only preventive anti-infective drugs, as before, but also drugs for the treatment of oncological, allergic and autoimmune diseases. However, it should be recognized that, despite the great intensity of research and the extremely high methodological and technological level of work carried out in these areas, real practically significant achievements in them are small.
The features of this period in the development of immunology include extremely high requirements for the methodological side of research, a clearly expressed applied orientation and an obvious disregard for theoretical generalizations. The experimental achievements of this period are very numerous, but their significance cannot always be assessed. Let's name just a few of them: deciphering the signaling pathways that ensure the activation of lymphocytes and innate immune cells; study of dendritic cells as cells connecting innate and adaptive immunity (many attempts are associated with dendritic cells practical application advances in immunology, in particular in the creation of vaccines various kinds); deciphering the factors and mechanisms that determine the distribution of cells in the body and the pathways of their recycling, as well as the homeostasis of lymphoid cells; discovery of mechanisms of formation of lymphoid organs; detection of heterogeneity of helper T lymphocytes and their connection with pathology; rediscovery of suppressor T cells (now as regulatory T cells), etc.
The largest theoretical generalization that entailed big number experimental research and practically significant developments, were the teachings of Ch. Janeway and his followers about the nature of recognition in innate immunity and the hierarchical interactions of innate and adaptive immunity. Wherein, Firstly, a new type of immunological recognition was discovered, which forced us to abandon the idea of the nonspecificity of innate immunity; secondly, the idea of the impossibility of launching adaptive immunity without prior activation of innate immunity was substantiated. Research carried out in the field of immunology in the twentieth! century, are more or less oriented towards this concept.
Currently, concerns are often expressed that immunology as an independent scientific discipline is disappearing, dissolving in molecular biology (a similar “dissolution” in microbiology was noted in the pre-war period). This is hardly possible, since immunology has its own object of research - specific interactions between antigens and their receptors that underlie self-foe discrimination - which has various manifestations and acquires more and more new aspects over time.
Immunology studies the structure and function of the immune system, its response to pathogens, the consequences of the immune response and how to influence them.
Immunology- (from Lat. immunis - free, liberated, freed from something + Greek lgpt - knowledge) - medical and biological science that studies the body’s reactions to foreign structures (antigens), the mechanisms of these reactions, their manifestations, course and outcome in norm and pathology, developing research and treatment methods based on these reactions.
SUBJECT OF STUDY OF IMMUNOLOGY
The structure of the immune system;
Patterns and mechanisms of development of immune reactions;
Mechanisms of control and regulation of immune reactions;
Diseases of the immune system and its dysfunction;
Conditions and patterns of development of immunopathological reactions and methods of their correction;
The ability to use the reserves and mechanisms of the immune system in the fight against infectious and non-infectious diseases;
Immunological problems of reproduction;
Immunological problems of organ and tissue transplantation.
MAIN TASKS immunology began: the study of the molecular mechanisms of immunity - both innate and acquired, the development of new vaccines and methods of treating allergies, immunodeficiencies, and cancer.
1.2. Immunology as a specific area of research arose from the practical need to combat infectious diseases. It is often divided into classical (old) and modern (new). This division is conditional, since the new immunology grew out of the classical one, which produced vaccinations against smallpox, rabies, anthrax, etc.
Several stages can be distinguished in the development of immunology:
Infectious(L. Pasteur and others), when the study of immunity to infections began.
There is evidence that the first smallpox vaccinations were carried out in China a thousand years before the birth of Christ. Inoculation the contents of smallpox pustules to healthy people in order to protect them from the acute form of the disease then spread to India, Asia Minor, Europe, the Caucasus and Russia.
Inoculation has been replaced by a method vaccinations(from the Latin “vacca” - cow), developed at the end of the 18th century. English doctor E. Jenner. He inoculated an 8-year-old boy, D. Phipps, with cowpox, and then 1.5 months later infected him with smallpox, as was done during inoculation.
The boy did not get sick. After 1.5 months, E. Jenner re-inoculated him, and again the boy remained healthy. In 1880 Louis Pasteur's article on protecting chickens from cholera by immunizing them with a pathogen with reduced virulence is published.
In 1881. Pasteur conducted a public experiment on inoculating 27 sheep with anthrax vaccine, and in 1885 he successfully tested a rabies vaccine on a boy bitten by a rabid dog.
In 1890. German physician Emil von Behring, together with Shibasaburo Kitasato, showed that antitoxins are formed in the blood of people who have had diphtheria or tetanus, which provide immunity to these diseases both to those who have been ill and to those to whom such blood will be transfused. In the same year, based on these discoveries, a method of treatment with blood serum was developed.
Non-infectious, after the discovery of blood groups by K. Landsteiner and
the phenomenon of anaphylaxis by C. Richet and P. Portier.
In 1900. Austrian physician and immunologist Karl Landsteiner discovered human blood groups, for which he was awarded the Nobel Prize in 1930.
In 1904 The famous chemist Svante Arrhenius proved the reversibility of the antigen-antibody interaction and laid the foundations of immunochemistry.
Cellular-humoral, which is associated with discoveries made by Nobel Prize winners:
I. I. Mechnikov - developed cell theory immunity (phagocytosis), P. Ehrlich—developed the humoral theory of immunity (1908).
F. Burnet and N. Ierne - created the modern clonal-selective theory of immunity (1960).
P. Medawar - discovered the immunological nature of allograft rejection (1960).
In 1883 Russian biologist and immunologist Ilya Mechnikov made the first report on the phagocytic theory of immunity. It was Mechnikov who stood at the origins of knowledge of the issues of cellular immunity. Mechnikov showed that the human body contains special amoeboid motile cells - neutrophils and macrophages, which absorb and digest pathogenic microorganisms. It was to them that he gave the primary role in protecting the body.
In 1891 An article by German pharmacologist Paul Ehrlich is published, in which he uses the term “antibody” to refer to antimicrobial substances in the blood.
The new stage in the development of immunology is associated primarily with the name of the outstanding Australian scientist M. Burnet (Macfarlane Burnet; 1899-1985). He considered immunity as a reaction aimed at differentiating everything “one’s own” from everything “alien”. It was Burnet who drew attention to the lymphocyte as the main participant in a specific immune response, giving it the name “immunocyte”. It was Burnet who predicted, and the Englishman Peter Medawar and the Czech Milan Hasek experimentally confirmed the state opposite to immune reactivity - tolerance. It was Burnet who pointed out the special role of the thymus in the formation of the immune response. And finally, Burnet remained in the history of immunology as the creator of the clonal selection theory of immunity (Fig. B.9). The formula of this theory is simple: one clone of lymphocytes is capable of responding only to one specific antigenic determinant.
Molecular genetic, characterized by outstanding discoveries that were awarded the Nobel Prize:
Robert Koch (1843-1910), who discovered the causative agent of tuberculosis and described the skin tuberculin reaction, also made a great contribution to the development of modern immunology; Jules Bordet (1870-1961), who made important contributions to the understanding of complement-dependent lysis of bacteria; Rodney Porter (1917-1985) and Gerald Edelman (1929), who studied the structure of antibodies; George Snell, Baruj Benacerraf and Jean Dausset, who described the major histocompatibility complex in animals and humans and discovered immune response genes