An English physician stood at the origins of immunology Jenner who developed a method of vaccination against smallpox. However, his research was of a private nature 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 a stable immunity to infections: he received and applied in 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 Bering- 1 winner of the Nobel Prize in Medicine (1901), awarded for the discovery of antitoxic antibodies and the development of tetanus and diphtheria sera.
Ehrlich- the founder of the theory of side chains (am in the form of receptors are located on the surface of cells, ar specifically selects the corresponding antibody receptors, ensures their release into circulation and compensatory hyperproduction of antibodies (receptors).
The doctrine of antigens - K. Landsteiner, J. Bordet, proved that ag can be not only microbes and viruses, but any animal cells. K. Landsteiner discovery of blood groups. (1930).
C. Richet- the discovery of anaphylaxis and allergies (1913).
Burnet and Meadovar(1960) - the doctrine of immunological tolerance, showed that the rejection of genetically foreign tissues and infectious immunity are based on the same mechanisms. M. Burnet is the creator of the clonal selection theory of immunity - one clone of lymphocytes is able to respond only to one specific antigenic determinant. And besides, Burnet is the author of one of the most important provisions of immunology - the concept of immunological supervision over the constancy of the internal environment of the body.
In the 60s, the doctrine of T- and B systems of immunity began to develop rapidly ( Claman, Davis, Royt).
The theory of 3-cell cooperation of immunocytes in the immune response ( Petrov, Royt and etc.). The main participants in the proposed scheme were T and B-lymphocytes and macrophages.
Decoding of the structure Ig - ( Porter, Eidelman)
Discovery of structures encoded by the GCG - ( Benaceraf, Snell)
Gene control of the immune response, the diversity of antibodies and the importance of some genes in predisposition to diseases
Obtaining monoclonal antibodies and substantiation of network regulation of immunogenesis ( Kohler, Milstein, Erne)
Currently, there is an intensive development of clinical immunology and the widespread introduction into practical medicine of the achievements of theoretical immunology (deciphering the pathogenesis of many diseases; creation of new classifications; classification of diseases of the immune system; development of methods of immunodiagnostics (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 the present- modern stage
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Immunology arose as a part of microbiology as a result of its practical application for the treatment of infectious diseases, therefore infectious immunology developed at the first stage.
Since its inception, immunology has closely interacted with other sciences: genetics, physiology, biochemistry, cytology. Over the past 30 years, it has become an extensive, independent fundamental biological science. Medical immunology practically solves most of the problems of diagnostics and treatment of diseases and in this respect it occupies a central place in medicine.
At the origins of immunology are the observations of ancient peoples. In Egypt and Greece, it was known that people did not get the plague again and therefore those who had recovered were involved in caring for the sick. Several centuries ago, in Turkey, in the Middle East, in China, for the prevention of smallpox, pus from dried smallpox abscesses was rubbed into the skin or mucous membranes of the nose. Such infection usually caused mild smallpox disease and rendered immune to reinfection. This method of preventing smallpox is called variolation. However, later it turned out that this method is far from safe, as it sometimes leads to severe smallpox and death.
For a long time, people have known that sick people who have suffered from cowpox do not get sick naturally. Over the course of 25 years, the English physician E. Jenner has verified this data by numerous studies and came to the conclusion that infection with cowpox prevents smallpox disease. In 1796, Jenner inoculated material from a smallpox abscess from a cowpox-infected woman into an eight-year-old boy. A few days later, the boy had a fever and abscesses appeared at the injection site of the infectious material. Then these phenomena disappeared. After 6 weeks, he was injected with pustule material from a patient with smallpox, but the boy did not get sick. With this experience, Jenner was the first to establish the possibility of preventing smallpox disease. The method became widespread in Europe, as a result of which the incidence of smallpox sharply decreased.
Scientifically based methods of preventing infectious diseases were developed by the great French scientist Louis Pasteur. In 1880, Pasteur studied chicken cholera. In one of the experiments, to infect chickens, he used an old culture of the causative agent of chicken cholera, which was stored for a long time at a temperature of 37 ° C. Some of the infected chickens survived, and after re-infection with a fresh culture, the chickens did not die. Pasteur reported this experiment to the Paris Academy of Sciences and suggested that weakened microbes could be used to prevent infectious diseases. Weakened crops are called vaccines (Vacca - cow), and the method of prevention - vaccination. Subsequently, Pasteur obtained vaccines against anthrax and rabies. The principles of obtaining vaccines and methods of their application developed by this scientist have been successfully used for over 100 years for the prevention of infectious diseases. However, how immunity is created was not known for a long time.
The development of immunology as a science was largely facilitated by the research of I. I. Mechnikov. By education, I. I. Mechnikov was a zoologist, worked in Odessa, then in Italy and in France, at the Pasteur Institute. While working in Italy, he experimented with starfish larvae, into which he injected rose thorns. At the same time, he observed that mobile cells accumulate around the thorns, enveloping and capturing them. I. I. Mechnikov developed the phagocytic theory of immunity, according to which the release of the body from microbes occurs with the help of phagocytes.
The second direction in the development of immunology was represented by the German scientist P. Ehrlich. He believed that the main defense mechanism against infection is serum humoral factors - antibodies. By the end of the 19th century, it became clear that these two points of view do not exclude, but mutually complement each other. In 1908, I. I. Mechnikov and P. Ehrlich were awarded the Nobel Prize for the development of the theory of immunity.
The last two decades of the 19th century were marked by outstanding discoveries in the field of medical microbiology and immunology. Antitoxic anti-tetanus and anti-diphtheria sera were obtained by immunizing rabbits with diphtheria and tetanus toxin. So, for the first time in medical practice, there was an effective remedy for the treatment and prevention of diphtheria and tetanus. In 1902, Bering was awarded the Nobel Prize for this discovery.
In 1885, Buchner and coworkers found that microbes do not multiply in fresh blood serum, that is, it has bacteriostatic and bactericidal properties. The substance contained in the whey was destroyed when heated and stored for a long time. Later Ehrlich called this substance complement.
The Belgian scientist J. Bordet showed that the bactericidal properties of serum are determined not only by complement, but also by specific antibodies.
In 1896, Gruber and Durham found that when animals were immunized with various microbes, antibodies are formed in the serum, which cause adhesion (agglutination) of these microbes. These discoveries expanded the understanding of the mechanisms of antibacterial protection and made it possible to apply the agglutination reaction for practical purposes. Already in 1895, Vidal used the agglutination test to diagnose typhoid fever. Somewhat later, serological methods for the diagnosis of tularemia, brucellosis, syphilis and many other diseases were developed, which are widely used in the clinic of infectious diseases at the present time.
In 1897, Krause discovered that, in addition to agglutinins, during the immunization of animals with microbes, precipitins are also formed, which combine not only with microbial cells, but also with the products of their metabolism. As a result, insoluble immune complexes are formed, which precipitate.
In 1899, Ehrlich and Morgenroth established that erythrocytes adsorb specific antibodies on their surface and, when complement is added to them, are lysed. This fact was important for understanding the mechanism of the antigen-antibody reaction.
The beginning of the 20th century was marked by a discovery that turned immunology from an empirical science into a fundamental one, and laid the foundation for the development of non-infectious immunology. In 1902, the Austrian scientist K. Landsteiner developed a method for conjugating haptens with carriers. This opened up fundamentally new possibilities for studying the antigenic structure of substances and the processes of antibody synthesis. Landsteiner discovered isoantigens of human erythrocytes of the ABO system and blood group. It became clear that there is a heterogeneity of the antigenic structure of different organisms (antigenic individuality), and that immunity is a biological phenomenon that is directly related to evolution.
In 1902, French scientists Richet and Portier discovered the phenomenon of anaphylaxis, on the basis of which the doctrine of allergy was subsequently created.
In 1923, Gleni and Ramon discovered the possibility of converting bacterial exotoxins under the influence of formalin into non-toxic substances - toxoid with antigenic properties. This made it possible to use toxoid as vaccine preparations.
Serological research methods are used in one more direction - for the classification of bacteria. Using antipneumococcal sera, Griffith in 1928 divided pneumococci into 4 types, and Lensfield, using antisera against group-specific antigens, classified all streptococci into 17 serological groups. Many types of bacteria and viruses have already been classified according to their antigenic properties.
A new stage in the development of immunology began in 1953 with the studies of the British scientists Billingham, Brent, Medavar and the Czech scientist Hasek on the reproduction of tolerance. Based on the idea expressed in 1949 by Burnet and further developed in Erne's hypothesis that the ability to distinguish between self and foreign antigens is not innate, but is formed in the embryonic and postnatal periods, Medavar and his co-workers at the beginning of the sixties acquired a tolerance to skin grafts in mice. Tolerance in sexually mature mice to donor skin grafts arose if they were injected with donor lymphoid cells in the embryonic period. Such recipients, having become sexually mature, did not reject skin grafts from donors of the same genetic line. For this discovery, Burnet and Medawar were awarded the Nobel Prize in 1960.
A sharp rise in interest in immunology is associated with the creation in 1959 of the clonal selection theory of immunity by F. Burnet, a researcher who made a huge contribution to the development of immunology. According to this theory, the immune system oversees the constancy of the cellular composition of the body and the destruction of mutant cells. Burnet's clonal selection theory became the basis for constructing new hypotheses and assumptions.
In the studies of L.A. Zilber and his collaborators, carried out in 1951-1956, a viral-immunological theory of the origin of cancer was created, according to which a provirus integrated into the genome of a cell causes its transformation into a cancer cell.
In 1959, the English scientist R. Porter studied the molecular structure of antibodies and showed that the gamma globulin molecule consists of two light and two heavy polypeptide chains connected by disulfide bonds.
Subsequently, the molecular structure of antibodies was clarified, the sequence of amino acids in the light and heavy chains was established, immunoglobulins were divided into classes and subclasses, and important data on their physicochemical and biological properties were obtained. For research on the molecular structure of antibodies R. Porter and the American scientist D. Edelman were awarded the Nobel Prize in 1972.
Back in the 30s, A. Komza discovered that the removal of the thymus leads to impaired immunity. However, the true significance of this organ was found out after in 1961 the Australian scientist J. Miller performed a neonatal thymectomy in mice, after which a specific syndrome of immunological deficiency, primarily of cellular immunity, developed. Numerous studies have shown that the thymus is the central organ of immunity. Interest in the thymus increased especially sharply after the discovery in the 70s of its hormones, as well as T - and B-lymphocytes.
1945-1955 a number of works have been published in which it was shown that when the lymphoepithelial organ, called the Fabrice's bag, is removed from birds, the ability to produce antibodies decreases. Thus, it turned out that there are two parts of the immune system - thymus-dependent, which is responsible for the reactions of cellular immunity, and dependent on the bag of Fabricius, which affects the synthesis of antibodies. J. Miller and the English researcher G. Claman in the 70s showed for the first time that in immunological reactions the cells of these two systems enter into cooperative interaction with each other. The study of cellular cooperation is one of the central directions of modern immunology.
In 1948 A. Fagreus established that antibodies are synthesized by plasma cells, and J. Gowens by transferring lymphocytes in 1959 proved the role of lymphocytes in the immune response.
In 1956, Jean Dosset and his co-workers discovered the HLA histocompatibility antigen system in humans, which made it possible to perform tissue typing.
McDewwitt in 1965 proved that genes of immunological reactivity (Ir-genes), on which the ability to respond to foreign antigens depends, belong to the main histocompatibility complex. In 1974 P. Zinkernagel and R. Dougherty showed that antigens of the main histocompatibility complex are the object of primary immunological recognition in the reactions of T-lymphocytes to various antigens.
The discovery in 1969 by D. Dumond of lymphokines produced by lymphocytes and the creation by N. Erne in 1974 of the theory of the immunoregulatory network "idiotype-anti-idiotype" was of great importance for understanding the mechanisms of regulation of the activity of immunocompetent cells and their interactions with auxiliary cells.
Along with the fundamental data obtained, new research methods were of great importance for the development of immunology. These include methods of culturing lymphocytes (P. Novell), quantitative determination of antibody-forming cells (N. Erne, A. Nordin), colony-forming cells (McCulloch), methods of culturing lymphoid cells (T. Meikinodan), detection of receptors on lymphocyte membranes. The possibilities of using immunological research methods and increasing their sensitivity have significantly increased in connection with the introduction of the radioimmunological method into practice. For the development of this method, the American researcher R. Yalow was awarded the Nobel Prize in 1978.
The development of immunology, genetics and general biology was greatly influenced by the hypothesis expressed in 1965 by W. Dreyer and J. Bennett that the light chain of immunoglobulins is encoded not by one, but by two different genes. Prior to this, the generally accepted hypothesis of F. Jacob and J. Monod, according to which the synthesis of each protein molecule is encoded by a separate gene.
The next stage in the development of immunology was the study of subpopulations of lymphocytes and thymus hormones, which have both stimulating and inhibitory effects on the immune process.
Proof of the existence of stem cells in the bone marrow that are capable of transforming into immunocompetent cells dates back to the period of the last two decades.
Achievements in immunology over the past 20 years have confirmed Burnet's idea that immunity is a homeostatic phenomenon and by its nature is directed primarily against mutant cells and autoantigens that appear in the body, and antimicrobial action is a particular manifestation of immunity. Thus, infectious immunology, which has been developing for a long time as one of the areas of microbiology, has become the basis for the emergence of a new area of scientific knowledge - non-infectious immunology.
The main task of modern immunology is to identify the biological mechanisms of immunogenesis at the cellular and molecular levels. The structure and functions of lymphoid cells, the properties and nature of the physicochemical processes occurring on their membranes, in the cytoplasm and organelles are investigated. As a result of these studies, today immunology has come close to understanding the intimate mechanisms of recognition, synthesis of antibodies, their structure and functions. Significant advances have been made in the study of T-lymphocyte receptors, cellular cooperation, and the mechanisms of cellular immune responses.
The development of immunology has led to the identification of a number of independent areas in it: general immunology, immunotolerance, immunochemistry, immunomorphology, immunogenetics, tumor immunology, transplant immunology, immunology of embryogenesis, autoimmune processes, radioimmunology, allergy, immunobiotechnology, environmental immunology, etc.
Pathogenic mycoplasmas and diseases caused by them.
Anthroponous human bacterial infections affecting the respiratory or genitourinary tract.
Mycoplasmas belong to the Mollicutes class, which includes 3 orders: Acholeplasmatales, Mycoplasmatales, Anaeroplasmatales.
Morphology: Absence of a rigid cell wall, cell polymorphism, plasticity, osmotic sensitivity, resistance to various agents that suppress cell wall synthesis, including penicillin and its derivatives. Gram "-", better stained according to Romanovsky-Giemsa; distinguish between moving and stationary types. The cell membrane is in a liquid crystalline state; includes proteins immersed in two lipid layers, the main component of which is cholesterol.
Cultural properties. Chemoorganotrophs, the main source of energy is glucose or arginine. They grow at a temperature of 30C. Most species are facultative anaerobes; extremely demanding on nutrient media and cultivation conditions. Culture media (beef heart extract, yeast extract, peptone, DNA, glucose, arginine).
Cultivated on liquid, semi-liquid and solid nutrient media.
Biochemical activity: Low. There are 2 groups of mycoplasmas: 1. decomposing with the formation of acid glucose, maltose, mannose, fructose, starch and glycogen; 2. oxidizing glutamate and lactate, but not fermenting carbohydrates. All species do not hydrolyze urea.
Antigenic structure: Complex, species-specific; the main AGs are represented by phospho- and glycolipids, polysaccharides and proteins; the most immunogenic are surface antigens, including carbohydrates in complex glycolipid, lipoglycan and glycoprotein complexes.
Pathogenic factors: adhesins, toxins, aggression enzymes and metabolic products. Adhesins are part of surface AGs and cause adhesion to host cells. It is assumed that some strains of M. pneumoniae have a neurotoxin, since often respiratory tract infections accompany lesions of the nervous system. Endotoxins have been isolated from many pathogenic mycoplasmas. In some species, hemolysins are found. Among the enzymes of aggression, the main factors of pathogenicity are phospholipase A and aminopeptidases, which hydrolyze the phospholipids of the cell membrane. Proteases that cause degranulation of cells, including mast cells, the breakdown of AT molecules and essential amino acids.
Epidemiology: M. pneumoniae colonizes the mucous membrane of the respiratory tract; M. hominis, M. genitalium u U. urealyticum - "urogenital mycoplasmas" - live in the urogenital tract.
The source of infection is a sick person. The transmission mechanism is aerogenic, the main transmission route is airborne.
Pathogenesis: Penetrate into the body, migrate through the mucous membranes, attach to the epithelium through glycoprotein receptors. Microbes do not show a pronounced cytopathogenic effect, but they cause disturbances in the properties of cells with the development of local inflammatory reactions.
Clinic: Respiratory mycoplasmosis - in the form of an upper respiratory tract infection, bronchitis, pneumonia. Extra-respiratory manifestations: hemolytic anemia, neurological disorders, complications from CVS.
Immunity: Respiratory and urogenital mycoplasmosis is characterized by repeated infections.
Microbiological diagnostics: nasopharyngeal swabs, sputum, bronchial lavages. With urogenital infections, urine, scrapings from the urethra, vagina are examined.
For laboratory diagnosis of mycoplasma infections, cultural, serological and molecular genetic methods are used.
In serodiagnostics, tissue smears, scrapes from the urethra, vagina, in which it is possible to detect AH of mycoplasmas in direct and indirect RIF, serve as material for research. Mycoplasmas and ureaplasmas are detected in the form of green granules.
AH mycoplasmas can also be found in the serum of patients. For this, ELISA is used.
For serodiagnosis of respiratory mycoplasmosis, specific AT are determined in paired sera of a patient. With urogenital mycoplasmosis, in some cases, serodiagnosis is performed, AT is determined most often in RPHA and ELISA.
Treatment. Antibiotics Etiotropic chemotherapy.
Prevention. Nonspecific
The main historical stages in the development of immunology and allergology. Modern sections of immunology and their importance for medicine.
Immunology studies the mechanisms and ways of protecting the body from genetically foreign substances - AG in order to maintain and maintain homeostasis, the structural and functional integrity of each organism and species as a whole. Chronologically, immunology as a science has gone through 2 large periods: trans. protoimmunology (from the ancient to the 80s of the 19th century), associated with spontaneous, empirical knowledge of the defense. r-th org-ma, and per. the birth of experimental and theoretical immunology (from the 80s of the 19th century to the second decade of the 20th century). During the second lane. completed the formation of the classic. immunology, cat. was mostly infectious. immun. The third period can also be distinguished (from the middle of the 20th century to the present day). During this period, the molecules developed. and cellular immunology, immunogenetics. Stages of development of microbiology: 1) The period of empirical. knowledge; 2) Morphological. period; 3) Physiological. period; 4) Immunologist.per .; 5) Molecular-genetic period. Immunological lane. (1st half of the 20th century) is the beginning of the development of immunology. It is associated with the names of the French. scientist L. Pasteur (discovered and developed the principles of vaccination), Russian biologist I.I. Mechnikov (discovered the phagocytic theory, which was the basis of cellular immunology) and the German doctor P. Ehrlich (expressed a hypothesis about AT and developed the humoral theory of immunity). It should be noted that as early as the empirical period, one discovery was made: Edward Jenner found a way to create immunity to arousal. smallpox man, by inoculating the man with the cowpox virus, i.e. the contents of the pustules of the bang, sick with cowpox. But only at the end of the 20th century did Pasteur scientifically substantiate the principles of vaccination and the method of obtaining vyktsin. He showed that the causative agent of chickens cholera, rabies, sib. Ulcers, which had lost the virulent pathogenic properties, had been preserved in one way or another. the ability, when introduced into the body, to create a specific. immunity to the pathogen. Pasteur first received from the brain of dogs and rabbits with rabies, subjected to. temperature exposure, live attenuated rabies vaccine using fixed rabies virus; checked the profile. and medical sv-va vktsiny on patients bitten by rabid alive .; created vaccination points. Mechnikov substantiated the doctrine of phagocytosis and phagocytes and proved that phagocytosis is observed in all animals, including protozoa, and manifests itself in relation to all foreign substances. This was the beginning of the cellular theory of immunity and the process of immunogenesis in general, taking into account cl. and humoral factors. In 1900. R. Koch discovered such a form of response of the immune system as HRT, and in 1905. S. Richet and Sakharov described GNT. Both of these forms of response formed the basis of the doctrine of allergy. In 1950. was open. hypertension tolerance and immunological memory. But the phenomenon is connected. with immunological memory (the rapid effect of the formation of antibodies upon repeated administration of antigens), first discovered growing. doctor Raisky 1915 Numerous studies have been devoted to the study. lymphocytes, their role in immunity, the relationship between T- and B-lymphocytes and phagocytes, the killer function of lymphocytes. At the same time, the page of immunoglobulins (Porter) was studied, interferon (Isaacs), interleukins were discovered. Immunology in the middle of the 20th century. took shape as a self. the science.
Allocate general and specific immunology. The general includes: molecular, cellular, physiology of immunity, immunochemistry, immunogenetics, evolutionary immunology. Private: immunoprophylaxis, allergology, immuno-oncology, transplantation them., Them. reproduction, immunopathology, immunobiotechnology., immunopharmacologist., ecological named., clinical named. Each section is private immun. plays a certain important role in medicine. Immun. permeates literally all of the profile. and clinical disciplines. and decides to exclude. important problems of medicine, such as reducing the frequency and elimination of infectious diseases, diagnosis and treatment of allergies, oncologist. ill., immunopathologist. comp., organ transplantation, etc. etc.
Immunology studies the structure and function of the immune system, its response to pathogens, the consequences of the immune response and how it can be influenced.
Immunology- (from Latin immunis - free, liberated, freed from anything + Greek privilege - knowledge) - biomedical science that studies the body's reactions to foreign structures (antigens), the mechanisms of these reactions, their manifestations, the 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;
Control mechanisms and regulation of immune responses;
Diseases of the immune system and its dysfunction;
Conditions and patterns of development of immunopathological reactions and methods of their correction;
The possibility of using 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 has become: the study of the molecular mechanisms of immunity - both congenital and acquired, the development of new vaccines and methods for the treatment of allergies, immunodeficiencies, and oncological diseases.
1.2. Immunology as a specific area of research arose from the practical need to combat infectious diseases. It is often divided into classic (old) and modern (new). This division is conditional, since the new immunology grew out of the classical one that 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 Christ. Inoculation 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 was replaced by the method vaccinations(from Lat. "vacca" - cow), developed at the end of the 18th century. by the English physician E. Jenner. He vaccinated an 8-year-old boy, D. Phipps, with vaccinia, 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 an article by Louis Pasteur on the protection of chickens from cholera by immunization with a pathogen with reduced virulence is published.
In 1881... Pasteur conducts a public experiment to inoculate 27 sheep with an anthrax vaccine, and in 1885 successfully tests a rabies vaccine on a boy bitten by a rabid dog.
In 1890... German physician Emil von Bering, 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 for those who have been ill and for those to whom such blood will be transfused. In the same year, on the basis of these discoveries, a method of treatment with blood serum was developed.
Non-infectious, after K. Landsteiner's discovery of blood groups and
the phenomenon of anaphylaxis by S. Richet and P. Porter.
In 1900... Austrian immunologist Karl Landsteiner discovered human blood groups, for which in 1930 he was awarded the Nobel Prize.
In 1904 g. the famous chemist Svante Arrhenius proved the reversibility of the antigen-antibody interaction and laid the foundations for immunochemistry.
Cellular-humoral, which is associated with the discoveries made by Nobel Prize winners:
II Mechnikov - developed the cellular theory of 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. Medavar - discovered the immunological nature of allograft rejection (1960).
In 1883 Russian biologist - immunologist Ilya Mechnikov made the first report on the phagocytic theory of immunity. It was Mechnikov who stood at the origins of the knowledge of the issues of cellular immunity. Mechnikov showed that in the human body there are special amoeboid mobile 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 g. an article by the German pharmacologist Paul Ehrlich was published, in which he used the term "antibody" to denote antimicrobial substances in the blood.
A new stage in the development of immunology is associated primarily with the name of the outstanding Australian scientist M. Burnet (Macfarlane Burnet; 1899-1985). Considered immunity as a reaction aimed at differentiating everything "ours" from everything "alien". It was Burnett 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 Medavar 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 for this theory is simple: one clone of lymphocytes is capable of responding to only one specific antigenic specific determinant.
Molecular genetic, characterized by outstanding discoveries that have been awarded the Nobel Prize:
A great contribution to the formation of modern immunology was also made by Robert Koch (Robert Koch; 1843-1910), who discovered the causative agent of tuberculosis and described the cutaneous tuberculin reaction; Jules Bordet (1870-1961), who made an important contribution to the understanding of complement-dependent lysis of bacteria; Rodney Porter (1917-1985) and Gerald Edelman (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 the immune response genes
PENZA STATE UNIVERSITY
Department "Microbiology, Epidemiology and Infectious Diseases"
Discipline : Medical Microbiology
Lecture
Lecture topic: INTRODUCTION TO IMMUNOLOGY. TYPES OF IMMUNITY. NON-SPECIFIC PROTECTION FACTORS
Target:
Get acquainted with the types and forms of immunity, study the nonspecific factors of the body's defense.
Plan:
Review questions:
Literature for preparation:
Vorobiev A.A., Bykov A.S., Pashkov E.P., Rybakova A. M ... Microbiology (Textbook) .- M: Medicine, 1998.
Medical Microbiology (Handbook), ed. V.I. Pokrovsky, D.K. Pozdeeva. - M: GOETAR, "Medicine", 1999.
Microbiology with Virology and Immunology / Edited by L.B. Borisov, A.M. Smirnova.-M., 1994
Microbiology and Immunology / Edited by A.A. Vorobyov. - M., 1999
Guide to laboratory studies in microbiology / Ed. LB Borisova. - M., 1984.
Virology. In 3 vols. / Edited by B. Filsz, D. Naip. - M, 1989.
L. Mesrovianu, E. Punescu, Physiology of Bacteria. - Bucharest: Publishing House of the Academy of Sciences RPRD960.
Viral, chlamydial and mycoplasma diseases. V.I. Kozlova and others - M .: "Avicenna", 1995.
Lecturer Mitrofanova N.N.
Immunology (from Latin immunity - immunity, immunity, logos - science) is a science that studies the ways and mechanisms of the body's defense against genetically foreign substances in order to maintain homeostasis.
In case of violation of homeostasis, infectious diseases, autoimmune reactions, and oncological processes develop.
The main function of the immune system is to recognize and destroy alien, genetically modified cells that have penetrated from the outside or formed in the body itself.
The development of immunology as a science can be divided into three stages.
1. The first stage (protoimmunology) is associated with the empirical development of infectious immunology
2. The second stage is the completion of the formation of classical immunology, the extension of the basic provisions of immunity to non-infectious processes (transplant and antitumor immunity) and the creation of a unified general biological theory of immunity.
3. The third stage - molecular genetic - (from the middle of the 20th century) the development of molecular and cellular immunology, immunogenetics.
The origins of the doctrine of immunity go back to ancient times and are associated with the observation that many, primarily children's, diseases, such as measles, chickenpox, mumps, etc., are not repeated. During this period, variolation methods were used to create immunity. After the introduction of a new method of protection against smallpox by the English rural doctor E. Jenner, a method of vaccination appeared. E. Jenner is sometimes called the "progenitor" of immunology.
However, having received a vaccine to protect against smallpox, he did not formulate general principles for creating immunity against any other infection.
The development of immunology began with the work of the outstanding French scientist L. Pasteur (1881). He and his students found methods to weaken (attenuate) the virulent properties of microorganisms, created vaccines with their help, and explained the mechanism of the formation of immunity when vaccines are administered. II Mechnikov (1882) discovered the phenomenon of phagocytosis and formulated the cellular (phagocytic) theory of immunity. At the same time, the French researchers E. Roux and A. Yersin (1888) established the ability of the causative agent of diphtheria to secrete a special toxin, to neutralize which the German scientist E. Bering and the Japanese researcher S. Kitazato (1890) developed a method for producing anti-diphtheria antitoxic immune serum. In Russia, such a serum was prepared by G. N. Gabrichevsky (1894). Were obtained antitoxic sera for the treatment of botulism, anaerobic gas infection, etc. A humoral theory of immunity arose, the founder of which was the German researcher P. Ehrlich.
The period of active specific prophylaxis of infectious diseases began. New vaccines were obtained from weakened live microorganisms for the prevention of tuberculosis (1919), plague (1931), yellow fever (1936), tularemia (1939), poliomyelitis (1954), etc. tetanus. Were introduced new methods for the diagnosis of infectious diseases based on the interaction of antigen - antibody.
In the 40s of the XX century, a new direction in immunology began to develop, associated with organ and tissue transplants. It is called transplant immunity. Its study was initiated by the work of J. Bordet and N. Ya. Chistovich (colleagues of II Mechnikov), who established that foreign erythrocytes and serum stimulate the production of antibodies. K. Landsteiner (1900) discovered blood groups and developed the theory of tissue isoantigens.
The English scientist P. Medovar (1945) put forward the postulate that immunity protects not only from microorganisms, but also from cells or tissues of a genetically foreign organism. It was clearly formulated that the process of rejection of transplanted foreign tissues is due to immunological mechanisms. New ideas about malignant neoplasms, specific tumor antigens [Zilber LA, 1944], antitumor immunity, new methods of treating tumors and allergies have emerged.
P. Medovar et al. (1953) and the Czech researcher M. Hasek (1960), studying transplant immunity, independently of each other discovered the phenomenon of immunological tolerance as a manifestation of tolerance for an alien, genetically different from "our own". Australian scientist F.M. Burnet and colleagues (1949) found that tolerance can be induced artificially by introducing a foreign antigen to an animal before birth. For this teaching, P. Medovar and M. Burnet were awarded the title of Nobel Prize winners.
The laws of inheritance of antigenic specificity, genetic control of the immune response, genetic aspects of tissue incompatibility during transplantation and problems of homeostasis of somatic cells of a macroorganism are being studied by a new branch of immunology - immunogenetics.
The development of immunology continues, and at the present stage, the organization of the immune system has been studied, the role of the thymus in the formation of cell populations (T- and B-lymphocytes), the mechanisms of their functioning, cooperative relationships between the main cells of the immune system have been identified, the structure of antibodies has been established (D. Edelman, R . Porter).
New phenomena of cellular immunity have been discovered (cytopathogenic action, allogeneic inhibition, the phenomenon of blast transformation, etc.).
The doctrine of hypersensitivity and immunodeficiency was created.
The forms of the immune response and factors of nonspecific protection have been studied.
Theories of immunity have been developed.
The creation of a unified general biological theory of immunity paved the way for its use in the fight for healthy longevity, taking as a basis the powerful natural resources of constitutional protection in the fight against infectious and many other diseases of humans and animals.
Immunity (from Latin immunitas - inviolable, protected, liberation, getting rid of the disease) is a system of biological protection of the internal environment of a multicellular organism (homeostasis) from genetically foreign substances of exogenous and endogenous nature.
This system ensures the structural and functional integrity of organisms of a particular species throughout their life. Genetically foreign substances ("not our own") enter the body from the outside in the form of pathogenic microorganisms and helminths, their toxins, proteins and other components, sometimes in the form of transplanted tissues or organs. Outdated, mutated or damaged cells of one's own organism can become "aliens".
The functions of the defense system, called the immune system, are the recognition of such foreign agents and a specific response to them.
Immunity is a multicomponent and diverse phenomenon in its mechanisms and manifestations. Two main defense mechanisms are known.
The first is due to the action of congenital, constitutive factors of nonspecific resistance (from lat. r esistentia - resistance) and is controlled by genetic mechanisms (innate, species immunity). They provide a non-selective response to the foreign agent. This means that the properties of such an agent are irrelevant. So, for example, a person is immune to the causative agents of dog distemper, chicken cholera, and animals are insensitive to Shigella, gonococcus and other microorganisms pathogenic to humans.
The second is determined by protective mechanisms that take place with the participation of the lymphatic system. They underlie the formation of individual adaptive (acquired) immunity acquired during life. Such immunity is characterized by the development of specific responses of the immune system to a specific foreign agent (i.e., it is inducible) in the form of the formation of immunoglobulins or sensitized lymphocytes. These factors are highly active and specific for action.
Depending on the methods of formation, several forms of acquired individual immunity are distinguished.
Acquired immunity can be formed as a result of an infectious disease, and then it is called natural active (post-infectious). Its duration ranges from several weeks and months (after dysentery, gonorrhea, etc.) to several years (after measles, diphtheria, etc.). Sometimes it can occur as a result of latent infection or carriage (for example, by "household" immunization for meningococcal infection). There are types of acquired immunity:
Antimicrobial is produced after a bacterial infection (plague, typhoid fever, etc.);
Antitoxic is formed as a result of the transferred toxicoinfection (tetanus, botulism, diphtheria, etc.);
Antiviral - after viral infections (measles, mumps, poliomyelitis, etc.);
Antiprotective - after infections caused by protozoa;
Antifungal - after fungal diseases.
In some cases, after an infectious disease, the macroorganism is completely freed from pathogens. Such immunity is called sterile. Immunity, in which pathogens persist indefinitely in the body of clinically healthy people who have undergone the disease, is called non-sterile.
Acquired immunity is transmitted from mother to child through the placenta during intrauterine development and is provided by immunoglobulins. It is called natural passive (transplacental). Its duration is 3-4 months, but it can be prolonged with breastfeeding of children, since antibodies are also contained in mother's milk. The importance of such immunity is great. It ensures the immunity of infants to infectious diseases.
Acquired artificial immunity results from immunization. Distinguish between active and passive forms of artificial immunity. Active artificial immunity develops after the introduction of weakened or killed microorganisms or their neutralized toxins into the body. At the same time, an active restructuring takes place in the body of warm-blooded animals, aimed at the formation of substances that have a detrimental effect on the pathogen and its toxins, there is a change in the properties of cells that destroy microorganisms and their waste products. The duration of this immunity is from 1 to 3-7 years.
Passive artificial immunity occurs when ready-made antibodies are introduced into the body, which are contained in the sera of animals specially immunized with certain types of pathogens (immune sera), or they are obtained from the sera of people who have been ill (immunoglobulins). This type of immunity arises immediately after the introduction of antibodies, but lasts only 15-20 days, then the antibodies are destroyed and removed from the body.
Factors of nonspecific resistance (protection), which provide a non-selective nature of the response to an antigen and are the most stable form of immunity, are due to the innate biological characteristics of the species. They react to a foreign agent in a stereotyped manner and regardless of its nature. The main mechanisms of nonspecific defense are formed under the control of the genome during the development of the organism and are associated with a wide range of natural physiological reactions - mechanical, chemical and biological.
Among the factors of nonspecific resistance are:
unresponsiveness of macroorganism cellsto pathogenic microorganisms and toxins, due to the genotype and associated with the absence on the surface of such cells of receptors for the adhesion of the pathogenic agent;
barrier function of the skin and mucous membranes,which is provided by the rejection of skin epithelial cells and active movements of the cilia of the ciliated epithelium of the mucous membranes. In addition, it is due to the release of exosecretions of the sweat and sebaceous glands of the skin, specific inhibitors, lysozyme, the acidic environment of gastric contents and other agents. Biological factors of protection at this level are due to the destructive effect of the normal microflora of the skin and mucous membranes on pathogenic microorganisms;
temperature reaction,at which the reproduction of most pathogenic bacteria stops. For example, the resistance of chickens to the causative agent of anthrax (B. anthracis) is due to the fact that their body temperature is in the range of 41-42 ° C, at which bacteria are not capable of self-reproduction;
cellular and humoral factors of the body.
In the case of the penetration of pathogens into the body, humoral factors are included, which include proteins of the complement system, properdin, lysines, fibronectin, the cytokine system (interleukins, interferons, etc.). Vascular reactions develop in the form of a rapid local edema in the focus of damage, which detains microorganisms and does not allow them to enter the internal environment. Acute phase proteins appear in the blood - C-reactive protein and mannan-binding lectin, which have the ability to interact with bacteria and other pathogens. In this case, their capture and absorption by phagocytic cells is enhanced, i.e., opsonization of pathogens occurs, and these humoral factors play the role of opsonins.
Cellular factors of nonspecific defense include mast cells, leukocytes, macrophages, natural (natural) killer cells (NK cells, from the English "natural killer").
Mast cells are large tissue cells that contain cytoplasmic granules containing heparin and biologically active substances such as histamine and serotonin. During degranulation, mast cells secrete special substances that mediate inflammatory processes (leukotrienes and a number of cytokines). Mediators increase the permeability of the vascular walls, which allows complement and cells to exit into the tissues of the lesion. All this inhibits the penetration of pathogens into the internal environment of the body. NK cells are large lymphocytes that do not have T- or B-cell markers and are capable of killing tumor and virus-infected cells spontaneously, without prior contact. In peripheral blood, they account for up to 10% of all mononuclear cells. NK cells are localized mainly in the liver, red pulp of the spleen, and mucous membranes.
Leukocytes contain powerful bactericidal factors and provide primary or pre-immune phagocytosis of microbial cells. Such leukocytes are called phagocytes (phagocytic cells). They are represented by monocytes, polymorphonuclear neutrophils and macrophages.
Phagocytosis - a biological phenomenon based on the recognition, capture, absorption and processing of foreign substances by a eukaryotic cell. The objects for phagocytosis are microorganisms, the body's own dying cells, synthetic particles, etc. Phagocytes are polymorphonuclear leukocytes (neutrophils, eosinophils, basophils), monocytes and fixed macrophages - alveolar, peritoneal, Kupffer cells, dendritic cells of the spleen Langerhans and others.
In the process of phagocytosis (from the Greek phago - I devour, cytos - cells) there are several stages (Fig. 15.1):
Approach of a phagocyte to a foreign corpuscular object (cell);
Adsorption of an object on the surface of a phagocyte;
Absorption of the object;
Destruction of the phagocytosed object.
The first phase of phagocytosis is carried out by positive chemotaxis.
Adsorption occurs by binding a foreign object to phagocyte receptors.
The third phase is carried out as follows.
The phagocyte envelops the adsorbed object with its outer membrane and draws (invaginates) it into the cell. Here a phagosome is formed, which then fuses with the lysosomes of the phagocyte. A phagolysosome is formed. Lysosomes are specific granules containing bactericidal enzymes (lysozyme, acid hydrolases, etc.).
Special enzymes are involved in the formation of active free radicals O 2 and H 2 O 2.
At the final stage of phagocytosis, the absorbed objects are lysis to low molecular weight compounds.
Such phagocytosis proceeds without the participation of specific humoral protective factors and is called pre-immune (primary) phagocytosis. It is this variant of phagocytosis that was first described by II Mechnikov (1883) as a factor of nonspecific defense of the organism.
Phagocytosis results in either the death of foreign cells (complete phagocytosis) or the survival and proliferation of captured cells (incomplete phagocytosis). Incomplete phagocytosis is one of the mechanisms of long-term persistence (experience) of pathogenic agents in a macroorganism and chronicity of infectious processes. Such phagocytosis often occurs in neutrophils and ends with their death. Incomplete phagocytosis was detected in tuberculosis, brucellosis, gonorrhea, yersiniosis and other infectious processes.
An increase in the speed and efficiency of the phagocytic reaction is possible with the participation of nonspecific and specific humoral proteins, which are called opsonins. These include proteins of the complement system C3 b and C4 b , proteins of the acute phase, IgG, IgM, etc. Opsonins have a chemical affinity for some components of the cell wall of microorganisms, bind to them, and then such complexes are easily phagocytosed because phagocytes have special receptors for opsonin molecules. The cooperation of various opsonins of blood serum and phagocytes constitutes the opsonophagocytic system of the body. Evaluation of the opsonic activity of blood serum is carried out by determining the opsonic index or opsonophagocytic index, which characterize the effect of opsonins on the absorption or lysis of microorganisms by phagocytes. Phagocytosis, in which specific (IgG, IgM) opsonin proteins are involved, is called immune.
Complement system(lat. complementum - supplement, means of replenishment) is a group of blood serum proteins that take part in nonspecific defense reactions: cell lysis, chemotaxis, phagocytosis, activation of mast cells, etc. Complement proteins belong to globulins or glycoproteins. They are produced by macrophages, leukocytes, hepatocytes and make up 5-10% of all blood proteins.
The complement system is represented by 20-26 blood serum proteins, which circulate in the form of separate fractions (complexes), differ in physical and chemical properties and are designated by the symbols C1, C2, C3 ... C9, etc. The properties and function of the main 9 components of complement are well studied ...
In the blood, all components circulate in an inactive form, in the form of coenzymes. The activation of complement proteins (i.e., the assembly of fractions into a single whole) is carried out by specific immune and nonspecific factors in the process of multistage transformations. Moreover, each component of the complement catalyzes the activity of the next. This ensures the sequence, the cascade of the entry of the complement components into the reaction.
The proteins of the complement system are involved in the activation of leukocytes, the development of inflammatory processes, the lysis of target cells and, by attaching to the surface of the cell membranes of bacteria, are able to opsonize (“dress”) them, stimulating phagocytosis.
There are 3 known ways to activate the complement system: alternative, classical and lectin.
The most important component of complement is C3, which is cleaved by the convertase produced by any activation pathway into C3 and C3 fragments. b. Fragment SZ b participates in the formation of C5-convertase. This is the initial stage in the formation of the membranolytic complex.
In an alternative pathway, complement can be activated by polysaccharides, bacterial lipipolysaccharides, viruses and other antigens without the participation of antibodies. The initiator of the process is the SZ component b which binds to the surface molecules of microorganisms. Further, with the participation of a number of enzymes and the protein properdin, this complex activates the C5 component, which attaches to the target cell membrane. Then a membrane-attacking complex (MAC) of C6-C9 components is formed on it. The process ends with membrane perforation and lysis of microbial cells. It is this pathway of starting a cascade of complementary proteins that takes place in the early stages of the infectious process, when specific immunity factors (antibodies) have not yet been developed. In addition, the SZ component b by binding to the surface of bacteria, it can act as an opsonin, enhancing phagocytosis.
The classical pathway of complement activation is triggered and proceeds with the participation of an antigen-antibody complex. IgM molecules and some IgG fractions in the antigen-antibody complex have special sites that are able to bind the C1 component of the complement. The C1 molecule consists of 8 subunits, one of which is an active protease. It participates in the cleavage of the C2 and C4 components with the formation of the C3-convertase of the classical pathway, which activates the C5 component and ensures the formation of the membrane-attacking complex C6-C9, as in the alternative pathway.
The lectin pathway of complement activation is due to the presence in the blood of a special calcium-dependent sugar-binding protein - mannan-binding lectin (MSL). This protein is able to bind mannose residues on the surface of microbial cells, which leads to the activation of a protease that cleaves components C2 and C4. This triggers the formation of a membrane-lysing complex, as in the classical complement activation pathway. Some researchers consider this path as a variant of the classical path.
In the process of cleavage of the C5 and C3 components, small fragments C5a and C3a are formed, which serve as mediators of the inflammatory reaction and initiate the development of anaphylactic reactions with the participation of mast cells, neutrophils and monocytes. These components are called complement anaphylatoxins.
The activity of complement and the concentration of its individual components in the human body can increase or decrease in various pathological conditions. There may be hereditary deficiencies. The complement content in animal sera depends on the species, age, season and even time of day.
The highest and most stable level of complement was observed in guinea pigs; therefore, native or lyophilized blood serum of these animals is used as a source of complement. The complement system proteins are very labile. They are rapidly destroyed when stored at room temperature, exposed to light, ultraviolet rays, proteases, solutions of acids or alkalis, removing Ca ++ and Mg ++ ions. Heating the serum at 56 ° C for 30 minutes leads to the destruction of complement, and this serum is called inactivated.
The quantitative content of complement components in the peripheral blood is determined as one of the indicators of the activity of humoral immunity. In healthy individuals, the content of the C1 component is 180 μg / ml, C2 - 20 μg / ml, C4 - 600 μg / ml, C3 - 13 001 μg / ml.
Inflammation, as the most important manifestation of immunity, develops in response to tissue damage (primarily integumentary) and is aimed at localizing and destroying microorganisms that have entered the body. The inflammatory response is based on a complex of humoral and cellular factors of nonspecific resistance. Clinically, inflammation is manifested by redness, swelling, pain, localized fever, and dysfunction of the damaged organ or tissue.
The central role in the development of inflammation is played by vascular reactions and cells of the mononuclear phagocyte system: neutrophils, basophils, eosinophils, monocytes, macrophages and mast cells. When cells and tissues are damaged, in addition, various mediators are released: histamine, serotonin, prostaglandins and leukotrienes, kinins, acute phase proteins, including C-reactive protein, etc., which play an important role in the development of inflammatory reactions.
The bacteria that entered the body after damage and their waste products activate the blood coagulation system, the complement system and the cells of the macrophage-mononuclear system. The formation of blood clots occurs, which prevents the spread of pathogens with blood and lymph and prevents the generalization of the process. When the complement system is activated, a membrane-attacking complex (MAC) is formed, which lyses microorganisms or opsonizes them. The latter enhances the ability of phagocytic cells to absorb and digest microorganisms.
The nature and outcome of the inflammatory process depend on many factors: the nature and intensity of the action of a foreign agent, the form of the inflammatory process (alternative, exudative, proliferative), its localization, the state of the immune system, etc. If the inflammation does not end within a few days, it becomes chronic and then immune inflammation develops with the participation of macrophages and T-lymphocytes.
