Identification of bacteria by antigenic structure. Bacterial antigens
Antigens of bacteria by localization are divided into capsular, somatic, flagellar and exoproduct antigens (Fig. 9.6).
Rice.
K - capsular, 1 - virulence, H - flagellate, 0 - somatic
Capsular antigens, or K antigens, are the outermost permanent structures on the surface of a microbial cell. According to their chemical structure, they are identified mainly as polysaccharides, although the former division of Escherichia K-antigens into L- and B-thermolabile antigens also allowed the protein nature of these structures. Their basis in pneumococci is made up of repeating sugars: D-glucose, O-galactose and L-rhamnose.
Antigenically, capsular polysaccharides are heterogeneous. In pneumonia streptococci, for example, more than 80 serological variants (serovars) are distinguished, which is widely used in diagnostic and therapeutic work. More homogeneous K-antigens of a polysaccharide nature include Uantigens of enterobacteria, Brucella, Francisella; polysaccharide-protein nature - Yersinia Y-Y antigens; protein nature - M-protein of group A streptococci, protein A of staphylococci, antigens K-88 and K-99 of Escherichia.
Other external structures with antigenic properties include the cord factor of mycobacteria, the polypeptide capsules of the anthrax microbe, but due to their variability they are not classified as capsular antigens.
Somatic antigens, or O-antigens, are side oligosaccharide chains of lipopolysaccharides (endotoxin) protruding above the surface of the cell wall of gram-negative bacteria. Terminal carbohydrate residues in side oligosaccharide chains can differ both in the order of arrangement of carbohydrates in the oligosaccharide chain and sterically. In fact, they are antigenic determinants. Salmonella has about 40 such determinants, up to four on the surface of one cell. According to their commonality, Salmonella are combined into O-groups. However, the specificity of Salmonella O-antigen is associated with dideoxyhexoses, among which paratosis, colitosis, abekvoz, tevelose, ascarylose, etc. were found. .
The outer polysaccharide part of the O-antigen (more precisely, endotoxin) is responsible for the antigenic bonds of enterobacteria, i.e. for non-specific serological tests, which can be used to identify not only the species, but also the strain of enterobacteria.
O antigens were called somatic when their exact localization was not yet known. In fact, both K- and O-antigens are surface, the difference is that the K-antigen shields the O-antigen. Hence it follows: before revealing the O-antigen, it is necessary to subject the suspension of the studied bacteria to thermal treatment.
Flagellar antigens, or H-antigens, are present in all motile bacteria. These antigens are thermolabile flagellum protein complexes that many enterobacteria possess. Thus, enterobacteria have two sets of antigenic determinants - strain-specific (O-antigen) and group-specific (H-antigen and K-antigen).
The complete antigenic formula of gram-negative bacteria is written in the sequence O: N: K. Antigens are the most stable markers of certain pathogens, which makes it possible to make a serious epizootological or epidemiological analysis.
Bacterial spores also have antigenic properties. They contain an antigen common to the vegetative cell and a spore antigen proper.
Thus, the permanent, temporary structures and forms of bacteria, as well as their metabolites, have independent antigenic properties, which, however, are characteristic of certain types of microorganisms. Since all of them are markers of the special structure of DNA in this type of bacteria, the surface of a microbial cell and its metabolites often contain common antigenic determinants.
The latter fact is important for improving methods for identifying microorganisms. So, for example, instead of a time-consuming, expensive and not always reproducible neutralization reaction, an express method based on the detection of surface determinants using immunofluorescence can be used to determine the serovars of the botulinum microbe.
Unlike antigens of other origin, so-called protective or protective antigens are distinguished among bacterial antigens. Antibodies developed against these antigens protect the organism of the given pathogenic microorganism. Capsular antigens of pneumococci, M-protein of streptococci, A-protein of staphylococci, protein of the second fraction of exotoxin of anthrax bacilli, protein molecules of the lower layers of the wall of some gram-negative bacteria, etc. have protective properties. Purified protective antigens do not have pyrogenic, allergenic properties, are well preserved and therefore approach ideal vaccine preparations.
Protective antigens determine the immunogenicity of microbial antigens. Antigens of not all microorganisms are able to create equally pronounced immunity. To increase the immunogenicity, in some cases, the antigen is mixed with adjuvants - nonspecific stimulators of mineral or organic immunogenesis. More often, aluminum hydroxide, aluminum-potassium alum, lanolin, vaseline oil, bacterial lipopolysaccharide, bordetell preparations, etc. are used for this purpose. adjuvant). Inoculation of humans with inactivated influenza and polio vaccines with incomplete Freund's adjuvant has confirmed their effectiveness. Similar adjuvants have been successfully used to enhance the immunogenicity of viral vaccines against FMD, parainfluenza type 3, Aujeszky's disease, canine distemper, infectious canine hepatitis, Gumboro disease, Newcastle disease, equine influenza, calf rotavirus diarrhea, and other diseases. Such vaccines cause a pronounced and prolonged immune response. Thanks to this, the effectiveness of vaccination is significantly increased and the number of annual vaccinations is reduced. Each adjuvant is injected into the body according to the instructions attached to it: subcutaneously, intramuscularly, intraperitoneally, etc.
The essence of the adjuvant action of these drugs is to prevent the entry of an antigen mixed with them into the body, which prolongs its immunizing effect, reduces reactogenicity, and in some cases causes blast transformation (Fig. 9.7).
Rice. 9.7.
Most adjuvants are capable of depositing antigen, ie. adsorb it on its surface and keep it in the body for a long time, which increases the duration of its effect on the immune system. However, the use of microbial adjuvants is avoided in the manufacture of antisera for immunochemical analysis, especially in order to establish the nature of antigens or antigenic bonds, since they reduce the specificity of the antisera. This happens due to the heterogeneity (or heterophilicity) of antigens, i.e. antigenic community of microbes of various taxonomic groups, tissues of plants, animals and humans.
The antigenic structure of microorganisms is very diverse. In microorganisms, there are common, or group, and specific, or typical, antigens.
Group antigens are common to two or more types of microbes belonging to the same genus, and sometimes belonging to different genera. So, common group antigens are present in certain types of the genus Salmonella; causative agents of typhoid fever have common group antigens with pathogens of paratyphoid A and paratyphoid B (0-1.12).
Specific antigens are present only in a given type of microbe, or even only in a certain type (variant) or subtype within a species. The determination of specific antigens makes it possible to differentiate microbes within a genus, species, subspecies, and even type (subtype). So, within the genus Salmonella, more than 2000 types of Salmonella have been differentiated according to the combination of antigens, and in the subspecies of Shigella Flexner - 5 serotypes (serovariants).
According to the localization of antigens in a microbial cell, there are somatic antigens associated with the body of the microbial cell, capsular - surface, or shell antigens and flagellar antigens located in the flagella.
Somatic, O-antigens(from German ohne Hauch - without breathing), are associated with the body of a microbial cell. In gram-negative bacteria, the O-antigen is a complex complex of lipid-polysaccharide-protein nature. It is highly toxic and is an endotoxin of these bacteria. In pathogens of coccal infections, Vibrio cholerae, brucellosis pathogens, tuberculosis and some anaerobes, polysaccharide antigens have been isolated from the body of microbial cells, which determine the typical specificity of bacteria. As antigens, they can be active in their pure form and in combination with lipids.
Flagella, H-antigens(from German Hauch - breath), are proteinaceous in nature and are found in the flagella of motile microbes. Flagellar antigens are rapidly destroyed by heating and by the action of phenol. They are well preserved in the presence of formalin. This property is used in the manufacture of killed diagnostic cums for the agglutination reaction, when it is necessary to preserve the flagella.
Capsular, K - antigens, - are located on the surface of the microbial cell and are also called superficial, or shell. They have been studied in most detail in microbes of the intestinal family, in which Vi-, M-, B-, L- and A-antigens are distinguished. Vi-antigen is of great importance among them. It was first discovered in strains of typhoid bacteria with high virulence and was called the virulence antigen. When a person is immunized with a complex of O- and Vi- antigens, a high degree of protection against typhoid fever is observed. The Vi antigen is destroyed at 60°C and is less toxic than the O antigen. It is also found in other intestinal microbes, such as Escherichia coli.
Protective(from Latin protectio - patronage, protection), or protective, antigen is formed by anthrax microbes in the body of animals and is found in various exudates in case of anthrax. The protective antigen is part of the exotoxin secreted by the anthrax microbe and is capable of inducing immunity. In response to the introduction of this antigen, complement-fixing antibodies are formed. A protective antigen can be obtained by growing the anthrax microbe on a complex synthetic medium. A highly effective chemical vaccine against anthrax was prepared from the protective antigen. Protective protective antigens have also been found in the pathogens of plague, brucellosis, tularemia, whooping cough.
Complete antigens cause in the body the synthesis of antibodies or the sensitization of lymphocytes and react with them both in vivo and in vitro. Full-fledged antigens are characterized by strict specificity, i.e., they cause in the body the production of only specific antibodies that react only with this antigen. These antigens include proteins of animal, plant and bacterial origin.
Defective antigens (haptens) are complex carbohydrates, lipids and other substances that are not capable of causing the formation of antibodies, but enter into a specific reaction with them. Haptens acquire the properties of full-fledged antigens only if they are introduced into the body in combination with a protein.
Typical representatives of haptens are lipids, polysaccharides, nucleic acids, as well as simple substances: dyes, amines, iodine, bromine, etc.
Vaccination as a method of preventing infectious diseases. The history of the development of vaccination. Vaccines. requirements for vaccines. Factors that determine the possibility of creating vaccines.
Vaccines are biologically active drugs that prevent the development of infectious diseases and other manifestations of immunopathology. The principle of using vaccines is to advance the creation of immunity and, as a result, resistance to the development of the disease. Vaccination refers to activities aimed at artificial immunization of the population by introducing vaccines to increase resistance to the disease. The purpose of vaccination is to create an immunological memory against a particular pathogen.
Distinguish between passive and active immunization. The introduction of immunoglobulins derived from other organisms is passive immunization. It is used for both therapeutic and prophylactic purposes. The introduction of vaccines is active immunization. The main difference between active immunization and passive immunization is the formation of immunological memory.
Immunological memory provides accelerated and more efficient removal of foreign agents when they reappear in the body. The basis of immunological memory are T- and B-memory cells.
The first vaccine got its name from the word vaccinia(vaccinia) is a viral disease of cattle. The English physician Edward Jenner first used the smallpox vaccine on the boy James Phipps, obtained from the vesicles on the hand of a patient with cowpox, in 1796. Only after almost 100 years (1876-1881) Louis Pasteur formulated the main principle of vaccination - the use of weakened preparations of microorganisms for formation of immunity against virulent strains.
Some of the live vaccines were created by Soviet scientists, for example, P. F. Zdrodovsky created a vaccine against typhus in 1957-59. The influenza vaccine was created by a group of scientists: A. A. Smorodintsev, V. D. Solovyov, V. M. Zhdanov in 1960. P. A. Vershilova in 1947-51 created a live brucellosis vaccine.
The vaccine must meet the following requirements:
● activate cells involved in antigen processing and presentation;
● contain epitopes for T- and T-cells, providing a cellular and humoral response;
● easy to be processed with subsequent effective presentation by histocompatibility antigens;
● induce the formation of effector T-cells, antibody-producing cells and corresponding memory cells;
● prevent the development of the disease for a long time;
● be harmless, that is, not cause serious illness and side effects.
The effectiveness of vaccination is actually the percentage of those vaccinated who responded to vaccination with the formation of specific immunity. Thus, if the effectiveness of a certain vaccine is 95%, then this means that out of 100 vaccinated, 95 are reliably protected, and 5 are still at risk of the disease. The effectiveness of vaccination is determined by three groups of factors. Factors that depend on the vaccine preparation: the properties of the vaccine itself, which determine its immunogenicity (live, inactivated, corpuscular, subunit, amount of immunogen and adjuvants, etc.); the quality of the vaccine product, i.e. the immunogenicity has not been lost due to the expiration date of the vaccine or due to the fact that it was not stored or transported correctly. Factors depending on the vaccinated: genetic factors that determine the fundamental possibility (or impossibility) of developing specific immunity; age, because the immune response is most closely determined by the degree of maturity of the immune system; health status "in general" (growth, development and malformations, nutrition, acute or chronic diseases, etc.); the background state of the immune system - primarily the presence of congenital or acquired immunodeficiencies.
Microbial identification is the determination of the systematic position of a culture isolated from a source to the level of a species or variant. In case of confidence in the purity of the culture isolated during the cultural method, they begin to identify it, relying on the keys (that is, a known list of enzymatic activity, a known antigenic structure), classification and characterization of type strains described in the manuals.
For identification purposes, a set of features is used: morphological(shape, size, structure, presence of flagella, capsules, spores, relative position in the smear), tinctorial(Gram stain and other methods), chemical(G+C in DNA and content, e.g., peptidoglycan, cellulose, chitin, etc.), cultural(nutritional requirements, conditions, rates and nature of growth on different media), biochemical(enzymatic degradation and transformation of various substances with the formation of intermediate and final products), serological(antigenic structure, specificity, associations), environmental(virulence, toxigenicity, toxicity, allergenicity of microbes and their products, the range of susceptible animals and other biosystems, tropism, interspecific and intraspecific relationships, the influence of environmental factors, including phages, bacteriocins, antibiotics, antiseptics, disinfectants).
When identifying microorganisms, it is not necessary to study all properties. Moreover, from an economic point of view, it is important that the range of tested tests is not more than necessary; it is also desirable to use simple (but reliable) tests available to a wide range of laboratories.
The identification of microorganisms begins with the assignment of culture to large taxa (type, class, order, family). To do this, it is often sufficient to determine the source of culture, morphological and cultural properties, Gram or Romanovsky-Giemsa stains. To establish the genus, species, and especially the variant, it is necessary to apply the definition of biochemical, serological, and ecological characteristics. Microbial identification schemes vary significantly. So, in the identification of bacteria, the emphasis is on biochemical and serological properties, fungi and protozoa - on the morphological features of cells and colonies. When identifying viruses, the method of molecular hybridization is used to establish the specificity of the genome, as well as special serological tests.
Biochemical identification of a pure culture of bacteria is carried out using differential diagnostic media. Differential diagnostic media contain a substrate for any enzyme detected in a microbe, and an indicator that fixes the change in the pH of the nutrient medium and stains it in colors characteristic of acidic or alkaline pH values (Fig. 2.1).
Fig.2.1. An example of the biochemical (enzymatic) activity of representatives of the Enterobacteriaceae family. An indicator, bromophenol blue, was added to the medium; at neutral pH values, the medium has a grassy green color; at acidic values, it is yellow; at alkaline pH values, it is blue. Indole is an alkaline product, the presence of urease is accompanied by the formation of urea (alkaline pH values), the fermentation of carbohydrates is accompanied by the formation of acid. A positive test for hydrogen sulfide is accompanied by blackening of the medium due to the action of a special reagent
Serological identification implies the determination of the antigenic specificity of the studied culture of microbes and the antigenic formula - a symbolic display of the antigenic structure of bacteria. For example, the antigenic structure of S. typhi is designated as O9,12:Vi:Hd; one of the E. coli serovars as O111:K58:H2. The antigenic formula is determined in an agglutination test on glass using a set of monoreceptor antisera, i.e. antibodies to specific bacterial antigens. As the studied antigens, a grown culture of bacteria is used, each microbe is a corpuscular antigen, which gives the phenomenon of agglutination when specific antibodies are added to it. Some problems arise in the study of capsular bacteria: the capsule shields the somatic antigen, so its bacterial culture is warmed up for the study. High temperature contributes to the destruction of the thermolabile capsule and the O-antigen becomes available for typing. Technique for setting up an agglutination reaction on glass. A drop of saline solution (control) and a drop of antiserum are applied to a clean, fat-free glass. If there are several antisera, then several glasses are taken. A microbial culture is introduced into each drop using a bacterial loop. Within 1-3 minutes, the appearance of agglutinates is observed, which are formed during the specific binding of certain antibodies to bacterial antigens and their subsequent association into large flakes visible to the eye.
Bacterial antigens:
group-specific (found in different species of the same genus or family)
species-specific (in different representatives of the same species);
type-specific (determine serological variants - serovars, antigenovars within one species).
Depending on the localization in the bacterial cell, K-, H-, O-antigens are distinguished (denoted by letters of the Latin alphabet).
O-AG - lipopolysaccharide of the cell wall of gram-negative bacteria. It consists of a polysaccharide chain (actually O-Ag) and lipid A.
The polysaccharide is thermostable (withstands boiling for 1-2 hours), chemically stable (withstands treatment with formalin and ethanol). Pure O-AG is weakly immunogenic. It shows structural variability and distinguishes many serovariants of bacteria of the same species. For example, each group of Salmonella is characterized by the presence of a certain O-AG (polysaccharide) - in group A
This is factor 2, group B has factor 4, and so on. In R-forms of bacteria, O-AG loses side chains
polysaccharide and type specificity.
Lipid A - contains glucosamine and fatty acids. It has strong adjuvant, non-specific immunostimulatory activity and toxicity. In general, LPS is an endotoxin. Already in small doses, it causes fever due to the activation of macrophages and the release of IL1, TNF and other cytokines, degranulocyte degranulation, and platelet aggregation. It can bind to any cells in the body, but especially to macrophages. In large doses, it inhibits phagocytosis, causes toxicosis, dysfunction of the cardiovascular system, thrombosis, endotoxic shock. LPS of some bacteria is part of immunostimulants (prodigiosan,
pyrogenal). Bacterial cell wall peptidoglycans have a strong adjuvant effect on SI cells.
H-AG is part of bacterial flagella, its basis is the flagellin protein. Thermolabile.
K-AG is a heterogeneous group of superficial, capsular AG bacteria.
They are in a capsule. They contain mainly acidic polysaccharides, which include galacturonic, glucuronic and iduronic acids. There are variations in the structure of these antigens, on the basis of which, for example, 75 types (serotypes) of pneumococci, 80 types of Klebsiella, etc. are distinguished. Capsular antigens are used to prepare meningococcal, pneumococcal, and Klebsiella vaccines. However, administration of high doses of polysaccharide antigens can induce tolerance.
Antigens of bacteria are also their toxins, ribosomes and enzymes.
Some microorganisms contain cross-reactive - antigenic determinants found in microorganisms and humans / animals.
In microbes of various species and in humans, there are common, similar in structure, AG. These phenomena are called antigenic mimicry. Often, cross-reactive antigens reflect the phylogenetic commonality of these representatives, sometimes they are the result of a random similarity in conformation and charges - AG molecules.
For example, Forsman's AG is found in barach erythrocytes, salmonella, and in guinea pigs.
Group A hemolytic streptococci contain cross-reacting antigens (in particular, M-protein) that are common with antigens of the endocardium and glomeruli of human kidneys. Such bacterial antigens cause the formation of antibodies that cross-react with human cells, which leads to the development of rheumatism and post-streptococcal glomerulonephritis.
The causative agent of syphilis has phospholipids similar in structure to those found in the heart of animals and humans. Therefore, the cardiolipin antigen of the heart of animals is used to detect antibodies to spirochete in sick people (Wassermann reaction).
Antigens of microorganisms
Each microorganism, no matter how primitive it may be, contains several antigens. The more complex its structure, the more antigens can be found in its composition.
In various microorganisms belonging to the same systematic categories, group-specific antigens are distinguished - they are found in different species of the same genus or family, species-specific - in various representatives of the same species and type-specific (variant) antigens - in different variants within the same and of the same kind. The latter are subdivided into serological variants, or serovars. Among bacterial antigens, there are H, O, K, etc.
Flagellar H-antigens. As the name implies, these antigens are part of the bacterial flagella. The H-antgen is a flagellin protein. It is destroyed by heating, and after treatment with phenol retains its antigenic properties.
Somatic O-antigen. Previously, it was believed that the O-antigen is enclosed in the contents of the cell, its soma, and therefore it was called the somatic antigen. Subsequently, it turned out that this antigen is associated with the bacterial cell wall.
The O antigen of Gram-negative bacteria is associated with cell wall LPS. The determinant groups of this cohesive complex antigen are the terminal repeating units of the polysaccharide chains connected to its main part. The composition of sugars in the determinant groups, as well as their number, is not the same in different bacteria. Most often they contain hexoses (galactose, glucose, rhamnose, etc.), amino sugar (M-acetylglucosamine). The O-antigen is thermally stable: it is preserved at boiling for 1-2 hours, it is not destroyed after treatment with formalin and ethanol. When animals are immunized with live cultures that have flagella, antibodies to O- and H-antigens are formed, and when immunized with a boiled culture, antibodies are formed only to the O-antgen.
K-antigens (capsular). These antigens are well studied in Escherichia and Salmonella. They, like O-antigens, are closely associated with the LPS of the cell wall and the capsule, but unlike the O-antigen, they contain mainly acid nolisaccharides: glucuronic, galacturonic, and other uronic acids. By sensitivity to temperature, K-antigens are divided into A-, B- and L-antigens. The most thermally stable are A-antigens that can withstand boiling for more than 2 hours. B-antigens can withstand heating at a temperature of 60°C for an hour, and L-antigens are destroyed when heated to 60°C.
K-antigens are located more superficially than O-antigens, and often mask the latter. Therefore, to detect O-antigens, it is necessary to first destroy K-antigens, which is achieved by boiling the cultures. The so-called Vi antigen belongs to the capsular antigens. It is found in typhoid and some other enterobacteria with high virulence, in connection with which this antigen is called the virulence antigen.
Capsular antigens of a polysaccharide nature were found in pneumococci, Klebsiella and other bacteria that form a pronounced capsule. Unlike group-specific O-antigens, they often characterize the antigenic features of certain strains (variants) of a given species, which are subdivided into serovars on this basis. In anthrax bacilli, the capsular antigen consists of polypeptides.
Antigens of bacterial toxins. Bacterial toxins have full antigenic properties if they are soluble compounds of a protein nature.
Enzymes produced by bacteria, including pathogenicity factors, have the properties of complete antigens.
protective antigens. First detected in the exudate of the affected tissue in anthrax. They have strongly pronounced antigenic properties that provide immunity to the corresponding infectious agent. Protective antigens are also formed by some other microorganisms when they enter the host organism, although these antigens are not their permanent components.
Virus antigens. Each virion of any virus contains different antigens. Some of them are virus-specific. The composition of other antigens includes components of the host cell (lipids, carbohydrates), which are included in its outer shell. The antigens of simple virions are associated with their nucleocapsids. According to their chemical composition, they belong to ribonucleoproteins or deoxyribonucleoproteins, which are soluble compounds and therefore are referred to as S-antigens (solutio-solution). In complexly organized virions, some antigenic components are associated with nucleocapsids, others with outer envelope glycoproteins. Many simple and complex virions contain special surface V-antigens - hemagglutinin and the enzyme neuraminidase. The antigenic specificity of hemagglutinin varies from virus to virus. This antigen is detected in the hemagglutination reaction or its variety - the hemadsorption reaction. Another feature of hemagglutinin is manifested in the antigenic function to cause the formation of antibodies - antigemashpotinins and enter into a hemagglutination inhibition reaction (HITA) with them.
Viral antigens can be group-specific, if they are found in different species of the same genus or family, and type-specific, inherent in individual strains of the same species. These differences are taken into account when identifying viruses.
Along with the listed antigens, antigens of the host cell may be present in the composition of viral particles. For example, an influenza virus grown on the allantoic membrane of a chicken embryo reacts with an antiserum prepared for the allantoic fluid. The same virus, taken from the lungs of infected mice, reacts with antisera to the lungs of these animals and does not react with antisera to allantoic fluid.
Heterogeneous antigens (heteroantigens). Common antigens found in representatives of various types of microorganisms, animals and plants are called heterogeneous. For example, Forsman's heterogeneous antigen is found in protein structures of guinea pig organs, in ram erythrocytes, and in salmonella.
human body antigens
All tissues and cells of the human body have antigenic properties. Some antigens are specific for all mammals, others are species-specific for humans, and others are for certain groups, they are called isoantigens (for example, blood group antigens). Antigens that are unique to a given organism are called alloantigens (Greek allos - another). These include tissue compatibility antigens - the products of the genes of the major tissue compatibility complex MHC (Major Histocompatiability Complex), characteristic of each individual. Antigens of different individuals that do not have differences are called syngeneic. Organs and tissues, in addition to other antigens, have organ and tissue antigens specific to them. The tissues of the same name in humans and animals have antigenic similarity. There are stage-specific antigens that appear and disappear at certain stages of tissue or cell development. Each cell contains antigens characteristic of the outer membrane, cytoplasm, nucleus and other components.
The antigens of each organism normally do not cause immunological reactions in it, since the body is tolerant to them. However, under certain conditions, they acquire signs of foreignness and become autoantigens, and the reaction against them is called autoimmune.
Tumor antigens and antitumor immunity. Cancer cells are variants of normal body cells. Therefore, they are characterized by antigens of those tissues from
which they originated, as well as antigens specific to the tumor and constituting a small proportion of all cell antigens. In the course of carcinogenesis, cell dedifferentiation occurs, therefore, the loss of some antigens, the appearance of antigens characteristic of immature cells, up to embryonic (fetoproteins) may occur. Tumor-specific antigens are specific only to a given type of tumor, and often to a tumor in a given individual. Tumors induced by viruses may have viral antigens that are the same for all tumors induced by a given virus. Under the influence of antibodies in a growing tumor, its antigenic composition may change.
Laboratory diagnosis of a tumor disease includes the detection of antigens characteristic of the tumor in blood sera. For this, the medical industry is currently preparing diagnostic kits containing all the necessary ingredients for the detection of antigens in enzyme immunoassay, radioimmunoassay, immunoluminescence analysis.
The body's resistance to tumor growth is provided by the action of natural killer cells, which make up 15% of all lymphocytes constantly circulating in the blood and all tissues of the body. Natural killers (NK) have the ability to distinguish any cells that have signs of foreignness, including tumor cells, from normal cells of the body and destroy foreign cells. In stressful situations, diseases, immunosuppressive effects, and some other situations, the number and activity of NKs decrease, and this is one of the reasons for the onset of tumor growth. During the development of a tumor, its antigens cause an immunological reaction, but it is usually insufficient to stop tumor growth. The reasons for this phenomenon are numerous and not well understood. These include:
low immunogenicity of tumor antigens due to their proximity to normal body antigens, to which the body is tolerant;
development of tolerance instead of a positive response;
the development of an immune response of the humoral type, while only cellular mechanisms can suppress the tumor;
immunosuppressive factors produced by a malignant tumor.
Chemotherapy and radiotherapy of tumors, stressful situations during surgical interventions can be additional factors that reduce the immune defense of the body. Measures to increase the level of antitumor resistance include the use of immunostimulating agents, cytokine preparations, stimulation of the patient's immunocytes in vitro with a return to the patient's bloodstream.
Isoantigens. These are antigens by which individual individuals or groups of individuals of the same species differ from each other.
In erythrocytes, leukocytes, platelets, as well as in the blood plasma of people, several dozen types of isoantigens have been discovered.
Genetically related isoantigens are combined into groups that have received the names: the LVO system, Rhesus, etc. The division of people into groups according to the ABO system is based on the presence or absence of antigens on erythrocytes, designated A and B. In accordance with this, all people are divided into 4 groups. Group I (0) - no antigens, group II (A) - erythrocytes contain antigen A, group
III (B) - erythrocytes have antigen B, group IV (AB) - erythrocytes have both antigens. Since there are microorganisms in the environment that have the same antigens (they are called cross-reacting), a person has antibodies to these antigens, but only to those that he does not have. The body is tolerant of its own antigens. Therefore, in the blood of persons of group I there are antibodies to antigens A and B, in the blood of persons of group II - anti-B, in the blood of persons of group III - anti-A, in the blood of persons
Group IV antibodies to A and Vantigens are not contained. When blood or erythrocytes are transfused to a recipient whose blood contains antibodies to the corresponding antigen, agglutination of transfused incompatible erythrocytes occurs in the vessels, which can cause shock and death of the recipient. Accordingly, people of group I (0) are called universal donors, and people of group IV (AB) are called universal recipients. In addition to antigens A and B, human erythrocytes may also have other isoantigens (M, M2, N, N2), etc. There are no isoantibodies to these antigens, and therefore, their presence is not taken into account during blood transfusion.
Antigens of the major tissue compatibility complex. In addition to antigens common to all people and group antigens, each organism has a unique set of antigens that are unique to itself. These antigens are encoded by a group of genes located on chromosome 6 in humans and are called antigens of the major tissue compatibility complex and are designated MHC antigens (English Major histocompatibility complex). Human MHC antigens were first discovered on leukocytes and therefore have a different name HLA (Human leucocyte antigens). MHC antigens are glycoproteins and are contained on the membranes of body cells, determining its individual properties and inducing transplantation reactions, for which they received a third name - transplantation antigens. In addition, MHC antigens play an indispensable role in inducing an immune response to any antigen.
MHC genes encode three classes of proteins, two of which are directly related to the functioning of the immune system and are discussed below, and class III proteins include complement components, TNF group cytokines, and heat shock proteins.
Class I proteins are found on the surface of almost all body cells. They consist of two polypeptide chains: the heavy chain is non-covalently linked to the second p chain. The chain exists in three variants, which determines the division of class antigens into three serological groups A, B and C. The heavy chain causes the contact of the entire structure with the cell membrane and its activity. Rchain is a microglobulin, the same for all groups. Each class I antigen is designated by a Latin letter and the serial number of this antigen.
Class I antigens ensure the presentation of antigens to cytotoxic C08+ lymphocytes, and the recognition of this antigen by antigen-presenting cells of another organism during transplantation leads to the development of transplantation immunity.
MHC class II antigens are located mainly on antigen-presenting cells - dendritic, macrophages, B lymphocytes. On macrophages and B lymphocytes, their expression sharply increases after cell activation. Class II antigens are divided into 5 groups, each of which contains from 3 to 20 antigens. Unlike class I antigens, which are detected in serological tests using sera containing antibodies to them, class II antigens are best detected in cellular tests - cell activation when the test cells are co-cultivated with standard lymphocytes.
