Allergy symptoms can take a person by surprise. Sometimes, they appear for the first time at a fairly mature age, in children or pregnant women. Not all allergic reactions develop instantly. In many cases, several days can pass between the body's response to an allergen. Especially often this situation occurs with allergic dermatitis. In modern medicine, a number of highly accurate analyzes are used to diagnose allergies.
Diagnostics is carried out both by in-vivo (inside the body) and in-vitro (outside the body) methods. Both of these methods have both advantages and disadvantages, the choice of a specific diagnostic method is determined by the patient's condition. The main representatives of the in-vivo method are skin and provocative tests. The in-vitro method is represented by a blood test for antibodies.
Skin tests
Skin tests are a special diagnostic examination technique for allergic diseases, which is based on observing the behavior of the skin in contact with allergens. There are various test panels that are used to identify a suspected allergen. The need to use all test panels is extremely rare. Basically, the range of suspected allergens is significantly narrowed when certain data are received from the patient, which indicate the nature of the alleged allergen.
Contraindications:
- Pregnancy and feeding;
- Early age of the child (up to 3 years);
- The presence of oncological diseases;
- Infectious diseases;
- AIDS, syphilis, tuberculosis;
- Diseases with skin manifestations;
- Active stage of allergy;
There are several options for skin testing. They are distinguished by the way they are carried out. This may include placing the allergen in small incisions or punctures, injecting with a syringe, or applying a special material soaked in allergen solutions. After that, the behavior of the skin area that interacts with the allergen is monitored. A positive reaction, with skin tests, is the appearance of various kinds of inflammation, blisters, rashes, skin irritations localized at the points of contact with the allergen.
It is important to remember that skin tests are a diagnostic method based on observing the occurrence of an allergic reaction. Therefore, before it is not used means to relieve the symptoms of allergies.
The preferred sites for skin testing are the forearm and back, since the skin in this area reacts to various allergens with a high degree of sensitivity.
Provocative tests
Provocative tests are a diagnostic method that gives the most exact result, about an allergic predisposition to a particular substance. These tests are provocative because the patient, with the help of the introduction of an allergen solution, determines the presence or absence of an allergy. Provocative tests can be carried out by drip, inhalation or orally, depending on the nature of the allergen.
In no case can you independently conduct such events. It must be understood that in this case we are not talking about the introduction of allergens in their pure form, but about their solutions in a minimum concentration that cannot be made independently. In addition, with provocative tests, there is a direct risk of complications, even if performed correctly.
The solutions used for instillation of the eyes, nose, inhalations have a different composition, as well as indicators of acid-base balance.
Blood tests for antibodies
Antibodies are proteins that take part in the development of allergic reactions. This diagnostic method is less accurate than in-vivo diagnostics, but it is completely safe, since the reaction of blood cells is monitored outside the body. Antibodies are proteins that are produced in response to allergens and combine with them to stimulate the production of histamine, which is essential for the development of allergy symptoms.
In order to take a blood test, it is mandatory to follow the doctor's instructions regarding dietary restrictions before the procedure. A blood test for allergies is necessarily performed on an empty stomach.
Antibodies in allergies show activity in different ways. Some are used to immediately cause immediate allergy symptoms (bronchial asthma, sneezing, inflammation of the eyes, etc.). Other. as in dermatitis are used to provoke reactions that develop in the long term. During an allergy, it is necessary to measure the levels of various allergens, as they may be involved in the development of allergy symptoms.
When analyzing for antibodies, it is necessary to carry out differential diagnostics with helminthic invasions, since they have a common symptomatic picture and test results.
IgE are antibodies of a general typology. They are found in large quantities in the venous blood, from where the material is taken. IgE provokes allergic reactions that occur urgently. The maximum interval between such reactions and direct contact with the allergen is a couple of hours. Basically, manifestations of allergic rhinitis, conjunctivitis, bronchial asthma and urticaria are associated with the work of this protein.
IgG are special antibodies that are involved in the formation of a delayed immune response. They are involved in the formation of symptoms of neurodermatitis. Most often they are involved in the formation of immune responses in food allergies.
A blood test for the production of antibodies is carried out in the laboratory. To do this, the blood material lends itself to contact with the alleged allergens, then when the allergen enters, the immune cells begin to produce antibodies.
Food Allergy Diagnosis
Of particular importance are the methods of diagnosing blood in cases of morbidity with food allergies. This is due to the slow nature of the immune response that occurs when a food allergen enters. If, with an allergy to pollen, symptoms develop already after 20 seconds after the allergen has entered, then with a food allergy, the immune response becomes noticeable only after 2-3 days. Food allergies, as such, are not treated. The use of medications only relieves the symptoms. The best way to avoid food allergies is to avoid foods that trigger them. Naturally, for this you need to know which foods cause allergies.
Diagnosis of the presence of special antibodies occurs under the action of special enzymes, due to which their laboratory observation becomes possible. The degree of severity of immune reactions ranges from 1 to 4x, where 4e is the highest allergenicity of the product. The list of probable allergen can be narrowed down after personal communication with the patient, during which the diet is clarified within 2 weeks. After that, the allergens of not consumed products are deleted from the diagnostic list.
Food allergy occurs with an increase in the level of IgG antibodies. After the allergen product ceases to be eaten, their level gradually returns to normal, which is observed during re-diagnosis, after 2-3 weeks.
The development of an allergic reaction to food products, may be associated with a violation of the integrity of the intestinal mucosa, which leads to the penetration of incompletely digested components. In this case, they bind to IgG antibodies. Such complexes are giant macromolecules that can disrupt the functioning of various organs and their systems.
Most often, this phenomenon occurs during the intake of alcoholic beverages, tobacco smoking, constant malnutrition, as well as due to the use of corticosteroids, as well as non-steroidal anti-inflammatory drugs.
With this development of an allergic reaction, it can be accompanied, in addition to the symptoms of food allergies: depression, weakness, gastrointestinal disorders, heart disorders, pain in the abdomen, migraine attacks.
General blood test for allergies
Allergies can also provoke various health problems that cause, in addition to special symptoms, general health problems. For this reason, it is mandatory to general analysis biochemical components of blood. Allergy symptoms can have much in common with the symptoms of diseases such as dysbacteriosis, various immunodeficiencies, as well as diseases provoked by helminthic activity. For this reason, first of all, a general blood test is performed, on the basis of which further diagnosis of allergies, as well as other diseases, is carried out.
A general blood test for allergies first of all allows you to determine the general state of immunity, which can serve as a basis for suspicion, both for allergic reactions and for other diseases or disorders that can both exclude allergic reactions and serve as concomitant diseases.
Blood is not only a transport organ, but also an organ of immunity, which may contain information about allergic reactions, inflammatory processes etc. When diagnosing allergies, the following indicators are important:
Their level rises when:
- Active stages of purulent inflammation;
- Burn conditions, traumatization of tissues with violation of their integrity;
- With rheumatism and oncology;
- In the postoperative period;
- Leukemia
Basophils are blood cells that are very rare. Their levels may increase with food allergies, as their inflammatory activity causes the development of symptoms of allergic dermatitis, which is also characteristic of drug allergies. The following states also occur as they level up:
- wind pox;
- anemia (hemolytic);
- nephrosis;
- colitis (ulcerative);
- surgery to remove the spleen
ANTIBODIES- proteins of the globulin fraction of blood serum of humans and warm-blooded animals, formed in response to the introduction of various antigens (bacteria, viruses, protein toxins, etc.) into the body and specifically interacting with the antigens that caused their formation. By binding to active sites (centers) with bacteria or viruses, antibodies prevent their reproduction or neutralize the toxic substances they release. The presence of antibodies in the blood indicates that the body has interacted with the antigen against the disease it causes. To what extent immunity depends on antibodies and to what extent antibodies only accompany immunity, is decided in relation to a particular disease. Determination of the level of antibodies in the blood serum makes it possible to judge the intensity of immunity even in cases where antibodies do not play a decisive protective role.
The protective effect of antibodies contained in immune sera is widely used in therapy and prevention. infectious diseases(see Seroprophylaxis, Serotherapy). Antibody reactions with antigens (serological reactions) are used in the diagnosis of various diseases (see Serological studies).
Story
For a long time about chem. nature A. knew very little. It is known that antibodies after the introduction of the antigen are found in the blood serum, lymph, tissue extracts and that they specifically react with their antigen. The presence of antibodies was judged on the basis of those visible aggregates that are formed when interacting with the antigen (agglutination, precipitation) or by changing the properties of the antigen (neutralization of the toxin, cell lysis), but almost nothing was known about the chemical substrate of the antibodies. .
Thanks to the use of methods of ultracentrifugation, immuno-electrophoresis and the mobility of proteins in an isoelectric field, antibodies have been proven to belong to the class of gamma globulins, or immunoglobulins.
Antibodies are normal globulins preformed during synthesis. Immune globulins obtained as a result of immunization of different animals with the same antigen and immunization of the same animal species with different antigens have different properties, just as serum globulins are not the same. various kinds animals.
Immunoglobulin classes
Immunoglobulins are produced by immunocompetent cells of lymphoid organs, they differ in mol. weight, sedimentation constant, electrophoretic mobility, carbohydrate content and immunological activity. There are five classes (or types) of immunoglobulins:
Immunoglobulins M (IgM): molecular weight about 1 million, have a complex molecule; the first to appear after immunization or antigenic stimulation, have a detrimental effect on microbes that have entered the bloodstream, contribute to their phagocytosis; weaker than immunoglobulins G, bind soluble antigens, bacterial toxins; are destroyed in the body 6 times faster than immunoglobulins G (for example, in rats, the half-life of immunoglobulin M is 18 hours, and immunoglobulin G is 6 days).
Immunoglobulins G (IgG): molecular weight of about 160,000, they are considered standard, or classic, antibodies: easily pass through the placenta; formed more slowly than IgM; most effectively bind soluble antigens, especially exotoxins, as well as viruses.
Immunoglobulins A (IgA): molecular weight of about 160,000 or more, produced by the lymphoid tissue of the mucous membranes, prevent the degradation of body cell enzymes and resist the pathogenic action of intestinal microbes, easily penetrate the body's cell barriers, are found in colostrum, saliva, tears, intestinal mucus, sweat, nasal discharge, in the blood are in smaller quantities, easily connect with the cells of the body; IgA appeared, apparently, in the process of evolution to protect the mucous membranes from bacterial aggression and transfer passive immunity to offspring.
Immunoglobulins E (IgE): molecular weight about 190,000 (according to R. S. Nezlin, 1972); apparently, they are allergic antibodies - the so-called reagins (see below).
Immunoglobulins D (IgD): molecular weight about 180,000 (according to R. S. Nezlin, 1972); at present, very little is known about them.
Structure of antibodies
The immunoglobulin molecule consists of two non-identical polypeptide subunits - light (L - from English light) chains with a molecular weight of 20,000 and two heavy (H - from English heavy) chains with a molecular weight of 60,000. These chains, connected by disulfide bridges, form the main monomer LH. However, such monomers do not occur in the free state. Most of the immunoglobulin molecules consist of dimers (LH) 2 , the rest - of polymers (LH) 2n . The main N-terminal amino acids of human gamma globulin are aspartic and glutamic, rabbit - alanine and aspartic acid. Porter (R. R. Porter, 1959), acting on immunoglobulins with papain, found that they decompose into two (I and II) Fab fragments and an Fc fragment (III) with a sedimentation constant of 3.5S and a molecular weight of about 50,000. carbohydrate is linked to the Fc fragment. At the suggestion of WHO experts, the following nomenclature of antibody fragments has been established: Fab fragment - monovalent, actively binding to the antigen; Fc fragment - does not interact with the antigen and consists of the C-terminal halves of the heavy chains; Fd-fragment - heavy chain region included in the Fab-fragment. The 5S pepsin hydrolysis fragment is proposed to be designated as F(ab) 2 , and the monovalent 3.5S fragment is designated as Fab.
Specificity of antibodies
One of the most important properties antibodies is their specificity, which is expressed in the fact that antibodies interact more actively and more fully with the antigen with which the body was stimulated. The antigen-antibody complex in this case has the greatest strength. Antibodies are able to distinguish slight changes in structure in antigens. When using conjugated antigens consisting of a protein and an included simple chemical- hapten, the resulting antibodies are specific to the hapten, the protein and the protein-hapten complex. Specificity is due to the chemical structure and spatial pattern of antideterminants of antibodies (active centers, reactive groups), that is, the sections of antibodies by which they are connected to the determinants of the antigen. The number of antideterminants of antibodies is often referred to as their valency. Thus, an IgM antibody molecule can have up to 10 valences, while IgG and IgA antibodies are divalent.
According to Karasha (F. Karush, 1962), IgG active centers consist of 10-20 amino acid residues, which is approximately 1% of all amino acids of an antibody molecule, and, according to Winkler (M. N. Winkler, 1963), active centers consist of 3-4 amino acid residues. Tyrosine, lysine, tryptophan, etc. were found in their composition. Antideterminants are apparently located in the amino-terminal halves of Fab fragments. Variable segments of light and heavy chains are involved in the formation of the active center, the latter playing the main role. It is possible that the light chain is only partially involved in the formation of the active center or stabilizes the structure of heavy chains. The most complete antideterminant is created only by a combination of light and heavy chains. The more coincidence points of association between antibody antideterminants and antigen determinants, the higher the specificity. Different specificity depends on the sequence of amino acid residues in the active site of antibodies. Coding the vast diversity of antibodies by their specificity is unclear. Porter admits three possibilities for specificity.
1. The formation of the stable part of the immunoglobulin molecule is controlled by one gene, and the variable part - by thousands of genes. Synthesized peptide chains are combined into an immunoglobulin molecule under the influence of a special cellular factor. The antigen in this case acts as a factor that triggers the synthesis of antibodies.
2. The immunoglobulin molecule is encoded by stable and variable genes. During the period of cell division, recombination of variable genes occurs, which determines their diversity and the variability of the regions of globulin molecules.
3. The gene encoding the variable part of the immunoglobulin molecule is damaged by a special enzyme. Other enzymes repair damage but, due to errors, allow for a different nucleotide sequence within a given gene. This is the reason for the different sequence of amino acids in the variable part of the immunoglobulin molecule. There are other hypotheses as well. Burnet (F. M. Burnet, 1971).
Heterogeneity (heterogeneity) of antibodies manifests itself in many ways. In response to the introduction of one antigen, antibodies are formed that differ in affinity for the antigen, antigenic determinants, molecular weight, electrophoretic mobility, and N-terminal amino acids. Group antibodies to various microbes cause cross-reactions to different types and types of Salmonella, Shigella, Escherichia, animal proteins, polysaccharides. The antibodies produced are heterogeneous in their specificity with respect to a homogeneous antigen or a single antigenic determinant. The heterogeneity of antibodies was noted not only against protein and polysaccharide antigens, but also against complex, including conjugated, antigens and against haptens. It is believed that the heterogeneity of antibodies is determined by the known microheterogeneity of antigen determinants. Heterogeneity can be caused by the formation of antibodies to the antigen-antibody complex, which is observed during repeated immunization, the difference in cells that form antibodies, as well as the belonging of antibodies to different classes of immunoglobulins, which, like other proteins, have a complex antigenic structure controlled genetically.
Types of antibodies
Complete antibodies have at least two active centers and, when combined with antigens in vitro, cause visible reactions: agglutination, precipitation, complement fixation; neutralize toxins, viruses, opsonize bacteria, cause the visual phenomenon of immune adhesion, immobilization, capsule swelling, platelet loading. Reactions proceed in two phases: specific (antibody-antigen interaction) and non-specific (one or another of the above phenomena). It is generally accepted that various serological reactions are due to one, not many antibodies and depend on the staging technique. There are thermal complete antibodies that react with the antigen at t ° 37 °, and cold (cryophilic), showing an effect at t ° below 37 °. There are also antibodies that react with the antigen at low temperatures, and a visible effect occurs at t ° 37 °; These are biphasic, biothermal antibodies, which include Donat-Landsteiner hemolysins. All known classes of immunoglobulins contain complete antibodies. Their activity and specificity are determined by the titer, avidity (see Avidity), the number of antideterminants. IgM antibodies are more active than IgG antibodies in hemolysis and agglutination reactions.
Incomplete antibodies(non-precipitating, blocking, agglutinoids), as well as complete antibodies, are able to combine with the corresponding antigens, but the reaction is not accompanied by the phenomenon of precipitation, agglutination, etc., visible in vitro.
Incomplete antibodies were found in humans in 1944 to the Rh antigen, they were found in viral, rickettsial and bacterial infections in relation to toxins in various pathological conditions. There is some evidence for the divalent nature of incomplete antibodies. Bacterial incomplete antibodies have protective properties: antitoxic, opsonizing, bacteriological; at the same time, incomplete antibodies have been found in a number of autoimmune processes - in blood diseases, especially hemolytic anemia.
Incomplete hetero-, iso- and autoantibodies can cause cell damage, as well as play a role in the occurrence of drug-induced leuko- and thrombocytopenia
Normal (natural) antibodies are usually found in the blood serum of animals and humans in the absence of overt infection or immunization. The origin of antibacterial normal antibodies can be associated, in particular, with antigenic stimulation by the normal microflora of the body. These views are theoretically and experimentally substantiated by studies on gnotobiont animals and newborns under normal living conditions. The question of the functions of normal antibodies is directly related to the specificity of their action. L. A. Zilber (1958) believed that individual resistance to infections and, in addition, "immunogenic readiness of the body" are determined by their presence. The role of normal antibodies in blood bactericidal activity, in opsonization during phagocytosis is shown. The works of many researchers have shown that normal antibodies are mainly macroglobulins - IgM. Some researchers have found normal antibodies in the IgA and IgG classes of immunoglobulins. They may contain both incomplete and complete antibodies (normal antibodies to erythrocytes - see Blood groups).
Synthesis of antibodies
Synthesis of antibodies proceeds in two phases. The first phase is inductive, latent (1-4 days), in which antibodies and antibody-forming cells are not detected; the second phase is productive (begins after the inductive phase), antibodies are found in plasma cells and fluid flowing from the lymphoid organs. After the first phase of antibody formation, a very rapid rate of growth of antibodies begins, often their content can double every 8 hours or even faster. The maximum concentration of various antibodies in the blood serum after a single immunization is recorded on the 5th, 7th, 10th or 15th day; after injection of deposited antigens - on the 21st - 30th or 45th day. Further, after 1-3 or more months, antibody titers fall sharply. However, sometimes low level antibodies after immunization is registered in the blood for a number of years. It has been found that primary immunization a large number various antigens is accompanied by the appearance of heavy IgM (19S) antibodies at first, then during short term- IgM and IgG(7S) antibodies and, finally, some light 7S antibodies. Re-stimulation of a sensitized organism with an antigen causes an acceleration in the formation of both classes of antibodies, a shortening of the latent phase of antibody formation, a shortening of the synthesis of 19S antibodies, and promotes the predominant synthesis of 7S antibodies. Often, 19S antibodies do not appear at all.
Pronounced differences between the inductive and productive phases of antibody formation are found in the study of their sensitivity to a number of influences, which is of fundamental importance for understanding the nature of specific prophylaxis. For example, irradiation prior to immunization is known to delay or completely inhibit antibody production. Irradiation in the reproductive phase of antibody formation does not affect the content of antibodies in the blood.
Isolation and purification of antibodies
In order to improve the method of isolation and purification of antibodies, immunosorbents have been proposed. The method is based on the conversion of soluble antigens into insoluble ones by attaching them through covalent bonds to an insoluble base of cellulose, Sephadex or other polymer. The method allows to obtain highly purified antibodies in large quantities. The process of isolating antibodies using immunosorbents includes three stages:
1) extraction of antibodies from immune serum;
2) laundering of the immunosorbent from nonspecific proteins;
3) cleavage of antibodies from the washed immunosorbent (usually buffer solutions with low pH values). In addition to this method, other methods for purifying antibodies are known. They can be divided into two groups: specific and non-specific. The former is based on the dissociation of antibodies from the complex insoluble antigen - antibody (precipitate, agglutinate). It is carried out by various substances; the method of enzymatic digestion of an antigen or flocculate toxin - antitoxin by amylase, trypsin, pepsin is widespread. Thermal elution is also used at t° 37-56°.
Non-specific methods of purification of antibodies are based on the isolation of gamma globulins: gel electrophoresis, chromatography on ion-exchange resins, fractionation by gel filtration through Sephadex. The method of precipitation with sodium sulfate or ammonium sulfate is widely known. These methods are applicable in cases of high serum antibody concentrations, such as hyperimmunization.
Gel filtration through Sephadexes, as well as the use of ion exchange resins, make it possible to separate antibodies according to the size of their molecules.
Application of antibodies
Antibodies, especially gamma globulins, are used for the treatment and prevention of diphtheria, measles, tetanus, gas gangrene, anthrax, leptospirosis, against staphylococci, rabies, influenza, etc. Specially prepared and purified diagnostic sera are used in the serological identification of infectious agents (see .Identification of microbes). It was found that pneumococci, staphylococci, salmonella, bacteriophages, etc., adsorbing the corresponding antibodies, stick to platelets, erythrocytes and other foreign particles. This phenomenon is called immune adhesion. It was shown that protein receptors of platelets and erythrocytes, which are destroyed by trypsin, papain and formalin, play a role in the mechanism of this phenomenon. The immune adhesion reaction is temperature dependent. It is measured by adherence of corpuscular antigen or by hemagglutination due to soluble antigen in the presence of antibodies and complement. The reaction is highly sensitive and can be used both to determine complement and very small (0.005-0.01 μg of nitrogen) amounts of antibodies. Immune adherence enhances phagocytosis by leukocytes.
Modern theories of antibody formation
There are instructive theories of antibody formation, according to which the antigen directly or indirectly participates in the formation of specific immunoglobulins, and theories that involve the formation of genetically preexisting antibodies to all possible antigens or cells that synthesize these antibodies. These include selection theories and the theory of repression - derepression, which allows the synthesis of any antibodies by one cell. Theories have also been proposed that seek to comprehend the processes of the immunological response at the level of the whole organism, taking into account the interaction of various cells and generally accepted ideas about protein synthesis in the body.
Gaurowitz-Pauling Direct Matrix Theory comes down to the fact that the antigen, having entered the cells that produce antibodies, plays the role of a matrix that influences the formation of an immunoglobulin molecule from peptide chains, the synthesis of which proceeds without the participation of the antigen. "Intervention" of the antigen occurs only in the second phase of the formation of the protein molecule - the phase of twisting of the peptide chains. The antigen changes the terminal N-amino acids of the future antibody (immunoglobulin or its individual peptide chains) in such a way that they become complementary to the determinants of the antigen and easily enter into contact with it. The antibodies formed in this way are cleaved from the antigen, enter the blood, and the released antigen takes part in the formation of new antibody molecules. This theory has raised a number of serious objections. It cannot explain the formation of immunological tolerance; exceeding the number of antibodies produced by the cell per unit of time for the many times smaller number of antigen molecules present in it; the duration of the production of antibodies by the body, calculated in years or a lifetime, compared with a much shorter period of preservation of the antigen in the cells, etc. fragments in antibody-synthesizing cells cannot be completely excluded. Recently Gaurovitz (F. Haurowitz, 1965) proposed a new concept, according to which the antigen changes not only the secondary, but also the primary structure of the immunoglobulin.
Theory of the indirect Burnet-Fenner matrix rose to prominence in 1949. Its authors believed that the macromolecules of the antigen and, most likely, its determinants penetrate the nuclei of germ-type cells and cause hereditary changes in them, which result in the formation of antibodies to this antigen. An analogy between the described process and transduction in bacteria is allowed. The new quality of formation of immune globulins acquired by cells is passed on to the offspring of cells in countless generations. However, the question of the role of the antigen in the described process turned out to be controversial.
It was this circumstance that caused the emergence of Jerne's theory of natural selection (K. Jerne, 1955).
Jerne's theory of natural selection. According to this theory, the antigen is not a template for the synthesis of antibodies and does not cause genetic changes in antibody-producing cells. Its role is reduced to the selection of available "normal" antibodies that spontaneously arise against various antigens. It seems to happen like this: the antigen, having entered the body, finds the corresponding antibody, combines with it; the resulting antigen-antibody complex is absorbed by the cells that produce antibodies, and the latter receive an incentive to produce antibodies of this kind.
Burnet's clonal selection theory(F. Burnet) appeared further development Yerne's ideas about selection, but not of antibodies, but of cells that produce antibodies. Burnet believes that as a result of the general process of differentiation in the embryonic and postnatal periods, many clones of lymphoid or immunologically competent cells are formed from mesenchymal cells, capable of reacting with various antigens or their determinants and producing antibodies - immunoglobulins. The nature of the response of lymphoid cells to the antigen in the embryonic and postnatal periods is different. The embryo either does not produce globulins at all, or synthesizes a little of them. However, it is assumed that those of its cell clones that are able to react with the antigenic determinants of their own proteins react with them and are destroyed as a result of this reaction. So, probably, the cells that form anti-A-agglutinins in people with blood group A and anti-B-agglutinins in people with blood group B die. If an antigen is injected into the embryo, then in a similar way it will destroy the corresponding cell clone and the newborn throughout his subsequent life will theoretically be tolerant to this antigen. The process of destruction of all cell clones to the embryo's own proteins ends by the time of its birth or exit from the egg. Now the newborn has only “his own”, and he recognizes any “foreign” that has entered his body. Burnet also allows the preservation of "forbidden" clones of cells capable of reacting with autoantigens of organs that have been isolated from antibody-producing cells during development. Recognition of "foreign" is provided by the remaining clones of mesenchymal cells, on the surface of which there are corresponding antideterminants (receptors, cellular antibodies) complementary to the determinants of the "foreign" antigen. The nature of receptors is genetically determined, that is, it is encoded in the chromosomes and is not introduced into the cell along with the antigen. The presence of ready-made receptors inevitably leads to the reaction of a given clone of cells with a given antigen, which now results in two processes: the formation of specific antibodies - immunoglobulins and the reproduction of cells of this clone. Burnet admits that a mesenchymal cell that has received antigenic irritation, in the order of mitosis, gives rise to a population of daughter cells. If such a cell settles in the medulla of the lymph node, it gives rise to the formation of plasma cells, when it settles in the lymphatic follicles - to lymphocytes, in the bone marrow - to eosinophils. Daughter cells are prone to somatic irreversible mutations. When calculated for the whole organism, the number of mutating cells per day can be 100,000 or 10 million, and, therefore, mutations will provide cell clones for any antigen. Burnet's theory aroused great interest among researchers and big number verification experiments. The most important confirmation of the theory was evidence of the presence on the precursors of antibody-producing cells (lymphocytes of bone marrow origin) of antibody-like receptors of an immunoglobulin nature and the presence in antibody-producing cells of the mechanism of intercistronic exclusion in relation to antibodies of various specificities.
The theory of repression and derepression formulated by Szilard(L. Szilard) in 1960. According to this theory, each cell that produces an antibody can potentially synthesize any antibody to any antigen, but this process is inhibited by a repressor of an enzyme involved in the synthesis of immunoglobulin. In turn, the formation of the repressor can be inhibited by the influence of the antigen. Szilard believes that the formation of antibodies is controlled by special non-replicating genes. Their number reaches 10,000 for each single (haploid) set of chromosomes.
Lederberg(J. Lederberg) believes that in the genes responsible for the synthesis of globulins, there are sites that control the formation of active centers of antibodies. Normally, the function of these areas is inhibited, and therefore the synthesis of normal globulins occurs. Under the influence of the antigen, and also, possibly, under the action of certain hormones, the activity of the gene sections responsible for the formation of active antibody centers is disinhibited and stimulated, and the cell begins to synthesize immune globulins.
According to H. N. Zhukova-Verezhnikova(1972), the evolutionary precursors of antibodies were protective enzymes similar to those that appear in bacteria with acquired antibiotic resistance. Like antibodies, enzymes consist of active (with respect to the substrate) and passive parts of the molecule. Due to economy, the mechanism "one enzyme - one substrate" was replaced by the mechanism of "single molecules with a varying part", that is, antibodies with variable active centers. Information about antibody formation is realized in the "reserve genes" zone, or in the "redundancy zone" on DNA. Such redundancy, apparently, can be localized in nuclear or plasmid DNA, which stores "evolutionary information ... that played the role of an internal mechanism that "roughly" controls hereditary variability." This hypothesis contains an instructive component, but is not completely instructive.
P. F. Zdrodovsky assigns the antigen the role of a derepressor of certain genes that control the synthesis of complementary antibodies. At the same time, the antigen, as Zdrodovsky admits in accordance with Selye's theory, irritates the adenohypophysis, resulting in the production of somatotropic (STG) and adrenocorticotropic (ACTH) hormones. STH stimulates the plasmacytic and antibody-forming response of lymphoid organs, which in turn are stimulated by the antigen, and ACTH, acting on the adrenal cortex, causes the release of cortisone by it. This latter in the immune organism inhibits the plasmacytic reaction of lymphoid organs and the synthesis of antibodies by cells. All these provisions have been confirmed experimentally.
The effect of the pituitary - adrenal glands on the production of antibodies can only be detected in a previously immunized organism. It is this system that organizes anamnestic serological reactions in response to the introduction of various nonspecific stimuli into the body.
An in-depth study of cellular changes during the immunological response and the accumulation of a large number of new facts substantiated the position according to which the immunological response is carried out only as a result of the cooperative interaction of certain cells. Accordingly, several hypotheses have been proposed.
1. Theory of cooperation of two cells. A lot of facts have been accumulated, indicating that the immunological response in the body is carried out under conditions of interaction between different types of cells. There is evidence that macrophages are the first to assimilate and modify the antigen, but subsequently “instruct” lymphoid cells to synthesize antibodies. At the same time, it was shown that there is cooperation between lymphocytes belonging to different subpopulations: between T-lymphocytes (thymus-dependent, antigen-reactive, originating from the thymus gland) and B-cells (thymus-independent, precursors of antibody-forming cells, bone marrow lymphocytes).
2. Theories of cooperation of three cells. According to the views of Roitt (I. Roitt) and others (1969), the antigen is captured and processed by macrophages. Such an antigen stimulates antigen-reactive lymphocytes, which undergo transformation into blastoid cells, which provide delayed-type hypersensitivity and turn into long-lived immunological memory cells. These cells enter into cooperation with antibody-forming progenitor cells, which in turn differentiate, proliferating into antibody-producing cells. According to Richter (M. Richter, 1969), most antigens have a weak affinity for antibody-forming cells, therefore, the following interaction of processes is necessary for the production of antibodies: antigen + macrophage - processed antigen + antigen-reactive cell - activated antigen + precursor of an antibody-forming cell - antibodies. In the case of a high affinity of the antigen, the process will look like this: antigen + precursor of antibody-forming cells - antibodies. It is assumed that under conditions of repeated stimulation with an antigen, the latter directly comes into contact with an antibody-forming cell or an immunological memory cell. This position is confirmed by the greater radioresistance of the repeated immunological response than the primary one, which is explained by the different resistance of the cells involved in the immunological response. Postulating the need for three-cell cooperation in antibody genesis, R. V. Petrov (1969, 1970) believes that antibody synthesis will occur only if the stem cell (the precursor of an antibody-forming cell) simultaneously receives a processed antigen from a macrophage, and an immunopoiesis inducer from an antigen-reactive cell, formed after its (antigen-reactive cell) stimulation with an antigen. If the stem cell comes into contact only with the antigen processed by the macrophage, then immunological tolerance is created (see Immunological tolerance). If there is a contact of a stem cell only with an antigen-reactive cell, then a nonspecific immunoglobulin is synthesized. It is assumed that these mechanisms underlie the inactivation of non-syngeneic stem cells by lymphocytes, since the immunopoiesis inducer, getting into an allogeneic stem cell, is an antimetabolite for it (syngeneic - cells with an identical genome, allogeneic - cells of the same species, but with a different genetic composition) .
Allergic antibodies
Allergic antibodies are specific immunoglobulins that are formed under the influence of allergens in humans and animals. This refers to the antibodies circulating in the blood during allergic reactions of the immediate type. There are three main types of allergic antibodies: skin-sensitizing, or reagins; blocking and hemagglutinating. The biological, chemical and physicochemical properties of human allergic antibodies are peculiar ( table.).
These properties differ sharply from the properties of precipitating, complement-fixing antibodies, agglutinins, and others described in immunology.
Reagins are commonly referred to as human homologous skin-sensitizing antibodies. This is the most important type of human allergic antibodies, the main property of which is the ability to carry out a reaction of passive transfer of hypersensitivity to the skin of a healthy recipient (see Prausnitz-Küstner reaction). Reagins have a number of characteristic properties that distinguish them from relatively well-studied immune antibodies. Many questions concerning the properties of reagins and their immunological nature remain, however, unresolved. In particular, the question of the homogeneity or heterogeneity of reagins in the sense of their belonging to a certain class of immunoglobulins is unresolved.
Blocking antibodies arise in patients with pollinosis in the course of specific hyposensitizing therapy to the antigen by which hyposensitization is performed. The properties of this type of antibody resemble those of precipitating antibodies.
Hemagglutinating antibodies are usually understood as human and animal blood serum antibodies that are capable of specifically agglutinating erythrocytes associated with a pollen allergen (indirect or passive hemagglutination reaction). The binding of the erythrocyte surface to the pollen allergen is achieved by a variety of methods, for example, with the help of tannin, formalin, double diazotized benzidine. Hemagglutinating antibodies can be detected in people with hypersensitivity to plant pollen, both before and after specific hyposensitizing therapy. In the process of this therapy, the negative reactions are transformed into positive ones or the titers of the hemagglutination reaction increase. Hemagglutinating antibodies have the ability to quickly adsorb on erythrocytes treated with pollen allergen, especially some of its fractions. Immunosorbents remove hemagglutinating antibodies faster than reagins. Hemagglutination activity is associated to some extent with skin sensitizing antibodies, but the role of skin sensitizing antibodies in hemagglutination seems to be small, since there is no correlation between skin sensitizing and hemagglutinating antibodies. On the other hand, there is a correlation between hemagglutinating and blocking antibodies in both pollen-allergic individuals and pollen-immunized healthy individuals. These two types of antibodies have many similar properties. In the process of specific hyposensitizing therapy, there is an increase in the level of both one and the other type of antibodies. Hemagglutinating antibodies to penicillin are not identical to skin sensitizing antibodies. The main reason for the formation of hemagglutinating antibodies was penicillin therapy. Apparently, hemagglutinating antibodies should be attributed to the group of antibodies referred to by a number of authors as “witness antibodies”.
In 1962, W. Shelley proposed a special diagnostic test based on the so-called degranulation of basophilic rabbit blood leukocytes under the action of an allergen reaction with specific antibodies. However, the nature of the antibodies that take part in this reaction and their relationship with circulating reagins are not well understood, although there is evidence of a correlation of this type of antibody with the level of reagins in patients with hay fever.
Establishing the optimal ratios of the allergen and the test serum is extremely important in practical terms, especially in studies with types of allergens, information about which is not yet contained in the relevant literature.
The following types of antibodies can be attributed to allergic antibodies of animals: 1) antibodies in experimental anaphylaxis; 2) antibodies in spontaneous allergic diseases of animals; 3) antibodies that play a role in the development of the Arthus reaction (such as precipitating). During experimental anaphylaxis, both general and local, special types of anaphylactic antibodies are found in the blood of animals, which have the property of passively sensitizing the skin of animals of the same species.
It has been shown that anaphylactic sensitization of guinea pigs with timothy grass pollen allergens is accompanied by the circulation of skin sensitizing antibodies in the blood. These skin sensitizing bodies have the property of performing homologous passive skin sensitization in vivo. Along with these homologous skin-sensitizing antibodies, with general sensitization of guinea pigs by timothy grass pollen allergens, antibodies circulate in the blood, which are detected by a passive hemagglutination test with bis-diazotized benzidine. Skin-sensitizing antibodies that carry out homologous passive transfer and have a positive correlation with an indicator of anaphylaxis are classified as homologous anaphylactic antibodies, or homocytotropic antibodies. Using the term "anaphylactic antibodies", the authors attribute to them a leading role in the anaphylaxis reaction. Studies began to appear confirming the existence of homocytotropic antibodies to protein antigens and conjugates in various types of experimental animals. A number of authors identify three types of antibodies involved in immediate allergic reactions. These are antibodies associated with a new type of immunoglobulin (IgE) in humans and similar antibodies in monkeys, dogs, rabbits, rats, mice. The second type of antibody is guinea pig-type antibodies that can bind to mast cells and isologous tissues. They differ in a number of properties, in particular, they are more thermally stable. It is believed that antibodies of the IgG type can also be a second type of anaphylactic antibodies in humans. The third type - antibodies that sensitize heterologous tissues, belonging, for example, in guinea pigs to the class γ 2 . In humans, only IgG type antibodies have the ability to sensitize guinea pig skin.
In animal diseases, allergic antibodies are described, which are formed during spontaneous allergic reactions. These antibodies are thermolabile and have skin-sensitizing properties.
Incomplete antibodies in forensic terms are used in the determination of antigens of a number of isoserological systems (see Blood groups) to establish blood belonging to a certain person in cases of criminal offenses (murder, sexual crimes, traffic accidents, bodily harm, etc.), as well as when examination of disputed paternity and motherhood. Unlike total antibodies, they do not cause erythrocyte agglutination in a saline medium. Among them, there are two types of antibodies. The first one is agglutinoids. These antibodies are able to cause erythrocytes to stick together in a protein or macromolecular environment. The second type of antibody is cryptagglutinoids, which react in the indirect Coombs test with antigammaglobulin serum.
To work with incomplete antibodies, a number of methods have been proposed, divided into three main groups.
1. Methods of conglutination. It has been noted that incomplete antibodies are capable of causing erythrocyte agglutination in a protein or macromolecular medium. As such media, blood serum of group AB (which does not contain antibodies), bovine albumin, dextran, biogel - specially purified gelatin, brought to a neutral pH by a buffer solution, etc. (see Conglutination) is used.
2. Enzymatic methods. Incomplete antibodies can cause agglutination of erythrocytes that have been previously treated with certain enzymes. Trypsin, ficin, papain, bread yeast extracts, proteinin, bromelain, etc. are used for this treatment.
3. Coombs test with antiglobulin serum (see Coombs reaction).
Incomplete antibodies related to agglutinoids can show their effect in all three groups of methods. Antibodies related to cryptagglutinoids are not able to agglutinate erythrocytes not only in saline, but also in the macromolecular environment, and block them in the latter. These antibodies are opened only in the indirect Coombs test, with the help of which not only antibodies related to cryptagglutinoids are opened, but also antibodies that are agglutinoids.
Monoclonal antibodies
From additional materials, volume 29
The classic way to produce antibodies for diagnostic and research purposes is to immunize animals with certain antigens and then obtain immune sera containing antibodies of the required specificity. This method has a number of disadvantages, primarily due to the fact that immune sera include heterogeneous and heterogeneous populations of antibodies that differ in activity, affinity (affinity for the antigen) and biological action. Conventional immune sera contain a mixture of antibodies that are specific both for the given antigen and for the protein molecules that contaminate it. A new type of immunological reagents are monoclonal antibodies obtained using clones of hybrid cells - hybridomas (see). The undoubted advantage of monoclonal antibodies is their genetically predetermined standard, unlimited reproducibility, high sensitivity and specificity. The first hybridomas were isolated in the early 70s of the 20th century, however, the actual development of an effective technology for creating monoclonal antibodies is associated with the studies of Koehler and Milstein (G. Kohler, C. Milstein), the results of which were published in 1975-1976. In the next decade, a new direction in cell engineering, associated with the production of monoclonal antibodies, was further developed.
Hybridomas are formed by the fusion of lymphocytes of hyperimmunized animals with cells transplanted by plasma cells of various origins. Hybridomas inherit from one of the parents the ability to produce specific immunoglobulins, and from the second - the ability to multiply indefinitely. Cloned populations of hybrid cells can long time to produce genetically homogeneous immunoglobulins of a given specificity - monoclonal antibodies. The most widely used monoclonal antibodies are produced by hybridomas obtained using the unique mouse cell line MOPC 21 (R3).
The formidable problems of monoclonal antibody technology include the complexity and laboriousness of obtaining stable, highly productive hybrid clones that produce monospecific immunoglobulins; the difficulty of obtaining hybridomas producing monoclonal antibodies to weak antigens that are unable to induce the formation of stimulated B-lymphocytes in sufficient quantities; the absence of some properties of immune sera in monoclonal antibodies, for example, the ability to form precipitates with complexes of other antibodies and antigens, on which many diagnostic test systems are based; low frequency fusion of antibody-producing lymphocytes with myeloma cells and limited stability of hybridomas in mass cultures; low stability during storage and increased sensitivity of monoclonal antibody preparations to changes in pH, incubation temperature, as well as to freezing, thawing and exposure to chemical factors; the difficulty of obtaining hybridomas or transplantable producers of human monoclonal antibodies.
Virtually all cells in a population of cloned hybridomas produce monoclonal antibodies of the same class and subclass of immunoglobulins. Monoclonal antibodies can be modified using cellular immune engineering techniques. Thus, it is possible to obtain “triomas” and “quadromes” producing monoclonal antibodies of dual specificity, change the production of pentameric cytotoxic IgM to the production of pentameric non-cytotoxic IgM, monomeric non-cytotoxic IgM or IgM with reduced affinity, and also switch (with preservation of antigenic specificity) IgM secretion to IgD secretion, and IgGl secretion to IgG2a, IgG2b or IgA secretion.
The mouse genome provides the synthesis of more than 1*10 7 different variants of antibodies that specifically interact with epitopes (antigenic determinants) of protein, carbohydrate or lipid antigens present in cells or microorganisms. It is possible to form thousands of different antibodies to one antigen, differing in specificity and affinity; for example, as a result of immunization with homogeneous human cells, up to 50,000 different antibodies are induced. The use of hybridomas makes it possible to select almost all variants of monoclonal antibodies that can be induced to a given antigen in the body of an experimental animal.
The variety of monoclonal antibodies obtained to the same protein (antigen) makes it necessary to determine their finer specificity. The characterization and selection of immunoglobulins with the required properties among the numerous types of monoclonal antibodies that interact with the antigen under study often turn into more laborious experimental work than the production of monoclonal antibodies. These studies include dividing a set of antibodies into groups specific to certain epitopes, followed by selection in each group of the optimal variant in terms of affinity, stability, and other parameters. To determine epitope specificity, the method of competitive enzyme immunoassay is most often used.
It is estimated that a primary sequence of 4 amino acids (the usual size of an epitope) can occur up to 15 times in the amino acid sequence of a protein molecule. However, cross-reactions with monoclonal antibodies occur at a much lower frequency than would be expected from these calculations. This happens because not all of these sites are expressed on the surface of the protein molecule and are recognized by antibodies. In addition, monoclonal antibodies only detect amino acid sequences in a specific conformation. It should also be taken into account that the sequence of amino acids in a protein molecule is not statistically distributed on average, and antibody binding sites are much larger than the minimum epitope containing 4 amino acids.
The use of monoclonal antibodies has opened previously inaccessible opportunities for studying the mechanisms of the functional activity of immunoglobulins. For the first time, using monoclonal antibodies, it was possible to identify antigenic differences in proteins that were previously serologically indistinguishable. New subtype and strain differences between viruses and bacteria were established, new cell antigens were discovered. With the help of monoclonal antibodies, antigenic relationships between structures were detected, the existence of which could not be reliably proved using polyclonal (ordinary immune) sera. The use of monoclonal antibodies made it possible to identify conservative antigenic determinants of viruses and bacteria, which have a wide group specificity, as well as strain-specific epitopes, which are characterized by great variability and variability.
Of fundamental importance is the detection of antigenic determinants using monoclonal antibodies that induce the production of protective and neutralizing antibodies to pathogens of infectious diseases, which is important for the creation of therapeutic and prophylactic drugs. The interaction of monoclonal antibodies with the corresponding epitopes can lead to the emergence of steric (spatial) obstacles to the manifestation of the functional activity of protein molecules, as well as to allosteric changes that transform the conformation of the active site of the molecule and block the biological activity of the protein.
Only with the help of monoclonal antibodies was it possible to study the mechanisms of the cooperative action of immunoglobulins, mutual potentiation or mutual inhibition of antibodies directed to different epitopes of the same protein.
Ascitic tumors of mice are more often used for the production of mass quantities of monoclonal antibodies. More pure preparations of monoclonal antibodies can be obtained on serum-free media in fermented suspension cultures or in dialysis systems, in microencapsulated cultures and devices such as capillary cultures. To obtain 1 g of monoclonal antibodies, approximately 0.5 l of ascitic fluid or 30 l of culture fluid incubated in fermenters with specific hybridoma cells is required. Under production conditions, very large quantities of monoclonal antibodies are produced. Significant costs for the production of monoclonal antibodies are justified by the high efficiency of protein purification on immobilized monoclonal antibodies, and the protein purification coefficient in a single-stage affinity chromatography procedure reaches several thousand. Affinity chromatography based on monoclonal antibodies is used in the purification of growth hormone, insulin, interferons, interleukins produced by genetically engineered strains of bacteria, yeast or eukaryotic cells.
The use of monoclonal antibodies in diagnostic kits is rapidly developing. By 1984, about 60 diagnostic test systems prepared using monoclonal antibodies were recommended for clinical trials in the USA. The main place among them is occupied by test systems for early diagnosis of pregnancy, determination of the content of hormones, vitamins, drugs in the blood, laboratory diagnostics of infectious diseases.
Criteria for the selection of monoclonal antibodies for their use as diagnostic reagents are formulated. These include high affinity for the antigen, allowing binding at low antigen concentrations, as well as effective competition with host antibodies already bound to antigens in the test sample; directed against an antigenic site usually not recognized by the antibodies of the host organism and therefore not masked by these antibodies; orientation against repetitive antigenic determinants of the surface structures of the diagnosed antigen; polyvalence, providing a higher activity of IgM compared to IgG.
Monoclonal antibodies can be used as diagnostic preparations for the determination of hormones and drugs, toxic compounds, markers of malignant tumors, for the classification and counting of leukocytes, for more accurate and rapid determination of blood grouping, for the detection of antigens of viruses, bacteria, protozoa, for the diagnosis of autoimmune diseases , detection of autoantibodies, rheumatoid factors, determination of immunoglobulin classes in blood serum.
Monoclonal antibodies make it possible to successfully differentiate the surface structures of lymphocytes and to identify with great accuracy the main subpopulations of lymphocytes, to classify cells into families of leukemias and human lymphomas. New reagents based on monoclonal antibodies facilitate the determination of B-lymphocytes and T-lymphocytes, subclasses of T-lymphocytes, turning it into one of the simple steps in calculating the blood formula. With the help of monoclonal antibodies, one or another subpopulation of lymphocytes can be selectively removed, turning off the corresponding function of the cellular immunity system.
Typically, diagnostic preparations based on monoclonal antibodies contain immunoglobulins labeled with radioactive iodine, peroxidase or another enzyme used in enzyme immunoassays, as well as fluorochromes, such as fluorescein isothiocyanate, used in the immunofluorescent method. The high specificity of monoclonal antibodies is of particular value in creating improved diagnostic products, increasing the sensitivity and specificity of radioimmunoassay, enzyme immunoassay, immunofluorescent methods of serological analysis, and antigen typing.
The therapeutic use of monoclonal antibodies can be effective when it is necessary to neutralize toxins of various origins, as well as antigenically active poisons, to achieve immunosuppression during organ transplantation, to induce complement-dependent cytolysis of tumor cells, to correct the composition of T-lymphocytes and immunoregulation, to neutralize bacteria resistant to antibiotics, passive immunization against pathogenic viruses.
The main obstacle to the therapeutic use of monoclonal antibodies is the possibility of developing adverse immunological reactions associated with the heterologous origin of monoclonal immunoglobulins. To overcome this, it is necessary to obtain human monoclonal antibodies. Successful research in this direction makes it possible to use monoclonal antibodies as vectors for the targeted delivery of covalently bound drugs.
Therapeutic drugs are being developed that are specific to strictly defined cells and tissues and have targeted cytotoxicity. This is achieved by conjugation of highly toxic proteins, such as diphtheria toxin, with monoclonal antibodies that recognize target cells. Directed by monoclonal antibodies, chemotherapeutic agents are able to selectively destroy tumor cells in the body that carry a specific antigen. Monoclonal antibodies can also act as a vector when incorporated into the surface structures of liposomes, which ensures the delivery of significant amounts of drugs contained in liposomes to target organs or cells.
The consistent use of monoclonal antibodies will not only increase the information content of conventional serological tests, but also prepare for the emergence of fundamentally new approaches to the study of the interaction of antigens and antibodies.
|
Researched parameters |
Types of antibodies |
||
|
skin-sensitizing (reagins) |
blocking |
hemagglutinating |
|
|
Principle of detection of antibodies |
Reaction with an allergen in the skin |
Blocking the allergen-reagin reaction in the skin |
The reaction of indirect hemagglutination in vitro |
|
Stability at t° 50° |
Thermolabile |
Thermostable |
Thermostable |
|
Ability to pass through the placenta |
Missing |
No data |
|
|
Ability to precipitate with 30% ammonium sulfate |
Do not precipitate |
besieged |
Partially precipitate, partly remain in solution |
|
Chromatography on DEAE-Cellulose |
Scattered across multiple factions |
In the 1st faction |
In the 1st faction |
|
Absorption by immuno-sorbents |
slow |
No data |
|
|
Precipitation with pollen allergens |
No, even after antibody concentration |
Yes, after antibody concentration |
Precipitating activity does not coincide with hemagglutinating |
|
Mercaptan inactivation |
going on |
Not happening |
No data |
|
Cleavage by papain |
Slow |
No data |
|
|
Sedimentation constant |
Over 7(8-11)S |
||
|
Electrophoretic Properties |
Predominantly γ1-globulins |
γ2-globulins |
Most associated with γ2-globulins |
|
Immunoglobulin class |
|||
Bibliography
Burnet F. Cellular immunology, trans. from English, M., 1971; Gaurovi c F. Immunochemistry and biosynthesis of antibodies, trans. from English, M., 1969, bibliography; Dosse J. Immunohematology, trans. from French, Moscow, 1959; Zdrodovsky P. F. Problems of infection, immunity and allergies, M., 1969, bibliogr.; Immunochemical analysis, ed. L. A. Zilbera, p. 21, M., 1968; Cabot E. and Meyer M. Experimental immunochemistry, trans. from English, M., 1968, bibliography; Nezlin RS Structure of antibody biosynthesis. M., 1972, bibliography; Nosse l G. Antibodies and immunity, trans. from English, M., 1973, bibliography; Petrov R. V. Forms of interaction of genetically different cells of lymphoid tissues (three-cell system of immunogenesis), Usp. modern biol., v. 69, c. 2, p. 261, 1970; Uteshev B. S. and Babichev V. A. Inhibitors of antibody biosynthesis. M., 1974; Efroimson V. P. Immunogenetics, M., 1971, bibliogr.
allergic a.- Ado A.D. Allergy, Multivol. Pat. physiol., ed. H. N. Sirotinina, v. 1, p. 374, M., 1966, bibliogr.; Ado A. D. General Allergology, p. 127, M., 1970; Polner A. A., Vermont I. E. and Serova T. I. To the question of the immunological nature of reagins in hay fever, in the book: Probl. allergol., ed. A. D. Ado and A. A. Podkolzina, p. 157, M., 1971; Bloch K. J. The anaphylactic antibodies of mammals including man, Progr. Allergy, v. 10, p. 84, 1967, bibliogr.; Ishizaka K. a. Ishizaka T. The significance of immunoglobulin E in reaginic hypersensitivity, Ann. Allergy, v. 28, p. 189, 1970, bibliogr.; Lichtenstein L. M., Levy D. A. a. Ishizaka K. In vitro reversed anaphylaxis, characteristics of anti-IgE mediated histamine release, Immunology, v. 19, p. 831, 1970; Sehon A. H. Heterogeneity of antibodies in allergic sera, in: Molec. a. celL basis of antibody formation, ed. by J. Sterzl, p. 227, Prague, 1965, bibliogr.; Stanworth D. R. Immunochemical mechanisms of immediate-type hypersensitivity reactions, Clin. exp. Immunol., U. 6, p. 1, 1970, bibliogr.
Monoclonal antibodies- Hybridomas: a new level of biological analysis, ed. R. G. Kennett et al., M., 1983; Rokhlin O. V. Monoclonal antibodies in biotechnology and medicine, in the book: Biotechnology, ed. A. A. Baeva, p. 288, M., 1984; N o w i n s k i R. C. a. o. Monoclonal antibodies for diagnosis of infectious diseases in humans, Science, v. 219, p. 637, 1983; Ollson L. Monoclonal antibodies in clinical immunobiology, Derivation, potential and limitations, Allergy, v. 38, p. 145, 1983; Sinko vies J. G. a. D r e e s m a n G. R. Monoclonal antibodies of hybridomas, Rev. infection. Dis., v. 5, p. 9, 1983.
M. V. Zemskov, N. V. Zhuravleva, V. M. Zemskov; A. A. Polner (all.); A. K. Tumanov (court); A. S. Novokhatsky (Monoclonal antibodies).
There are two types of antibodies - immune and allergic. Allergic antibodies are distinguished by their ability to bind to cells and increase their sensitivity to the action of allergens (sensitize). There are three types of allergic antibodies: 1) homocytotropic (reagins); 2) blocking; 3) hemagglutinating (witness antibodies). Reagins are the main type of human allergic antibodies, and they will be discussed further. Blocking antibodies (Ig G) are produced during the recovery period and in response to the introduction of subthreshold doses of the allergen. They have a stronger affinity for the allergen than reagins, and therefore play a protective role, preventing the interaction of the allergen with reagins on cells. The role of hemagglutinating antibodies in the development of AR has not been fully disclosed. Their titer increases with exacerbation of allergic diseases. They can circulate in the blood or be fixed on cells (for example, red blood cells). Unlike reagins, they are not firmly fixed on the cells.
The second population of HCAs includes subclasses of Ig G. These reagins are capable of short-term skin sensitization. They are characterized by low affinity for their cellular receptors and are resistant to heating and reducing agents. However, they, like Ig E, may be involved in some type I hypersensitivity reactions in humans.
It should be noted that most (if not all) people have the ability to produce allergic antibodies. So, in the blood of almost everyone suffering from ascariasis, reagins are found. However, external manifestations of the disease are found only in some of them. Thus, the formation of allergic antibodies is mandatory, but not the only condition for an allergic disease. Much depends on the permeability of membranes, the ability of cells to fix antibodies and produce biologically active substances, and the sensitivity of tissues to these substances. On the other hand, it is known that the higher the concentration of allergic antibodies in the blood, the more rapidly AR proceeds, and this, in turn, depends both on the hereditary program and on the influence of environmental factors.
target cells
Allergens, getting into a sensitized organism, attach to allergic antibodies fixed on the membrane of mast cells, blood basophils, capillary endothelium, nerve and muscle cells. These cells are called target cells. The first-order target of allergy is mast cells (MCs). Typical connective tissue TCs are localized along blood vessels. In humans, the skin and gastrointestinal tract (GIT) are especially rich in them. A characteristic feature of MCs and basophils is the presence of high-affinity receptors for Ig E. This type of receptor differs from the low-affinity ones present on other allergy target cells. TCs are heterogeneous. They differ in sensitivity to different activators. uneven distribution different types TC along the digestive canal affects the features of AR in different parts of the gastrointestinal tract. At one time, it was believed that during the Allergen + antibody reaction to MCs, they are damaged. It turned out that they are not damaged, but are excited and release biologically active substances. The main subsequent changes are associated with the action of these biologically active substances. BAS secreted by TC and basophils attract many cells into the reaction zone Allergen + antibody (A + a) - eosinophils, neutrophils, monocytes, lymphocytes, platelets. These cells also have receptors for Ig E. These cells, in turn, also secrete a large number of BAS. Their "task" is the organization of allergic inflammation for the localization, inactivation and removal of the allergen.
The leading role among these cells is played by eosinophils, which are called the second-order target. Intercellular interactions in AR are not linear, but consist in the mutual influence of cells on each other. The AR contains processes aimed at stopping and reversing the development of allergic inflammation. It is this mission that is called upon to fulfill
Eosinophils that secrete biologically active substances that inactivate pro-inflammatory mediators of TK and basophils and phagocytize immune complexes (A + a). Eosinophils play a leading role in the reaction of the late phase of the allergic response, which occurs in the experiment 4-6 hours after the permissive allergen injection in the form of edema and redness. This phase, which sometimes lasts up to 48 hours, is characterized by infiltration of tissues by eosinophils, neutrophils, and mononuclear cells. The late phase is now considered as a continuation of the immediate reaction to the allergen, associated with the gradual production of biologically active substances by secondary target cells. Many well-known signs of allergy (bronchial infiltration with eosinophils, accumulation of products of eosinophilic origin in the sputum of patients with bronchial asthma, infiltration of other tissues with eosinophils, an increase in the content of these cells in mucous secretions and in the blood) indicate a significant role of eosinophils in the development of AR.
Complete antibodies- These are antibodies that have 2 or more active centers. After their connection with the antigen, a visible precipitate (agglutinate, precipitate) is formed.
Incomplete antibodies are antibodies that have a single active site. They are able to bind to antigens, but this is not accompanied by visible changes.
Normal antibodies- these are antibodies that are constantly present in humans and animals without getting into the body of the antigen (without immunization). These include, for example, blood plasma antibodies (agglutinins), which determine the division of human blood into 4 groups.
Lecture No. 15 The immune system of the human body. Antibody formation. Allergy.
The immune system is a system of organs and cells that protect against genetically alien agents (antigens), including microbial ones.
The immune system is made up of lymphoid tissue. The main cells of this tissue are called lymphocytes. The total mass of lymphoid tissue in the body of an adult is 1.5 - 2 kg, and the number of lymphocytes is 10 13. The immune system includes lymphoid organs, which have a specific internal structure, and cells that circulate in the blood and lymph.
Lymphoid tissues are divided into central and peripheral.
Central authorities: thymus(thymus) and Bone marrow. In birds, the central organ is a bag(bursa) Fabricius. In the central organs, the formation, maturation and "training" of lymphocytes take place, which then (after acquiring immune competence) enter the circulation (into the blood and lymph) and populate the peripheral organs. are formed in the thymus T-lymphocytes, and in the bone marrow and in the bag of Fabricius - B-lymphocytes.
Peripheral organs: spleen, lymph nodes, palatine tonsils, adenoids, appendix, Peyer's patches of the intestine, group lymphatic follicles of the genitourinary, respiratory tracts and other organs, blood and lymph. The cells of these organs, under the influence of antigens, directly carry out all reactions of cellular and humoral immunity (the formation of antibodies, sensitized T-lymphocytes), therefore these cells are called immunocompetent or immunocytes.
There are 3 types of immune cells: macrophages, T-lymphocytes and B-lymphocytes.
These cells are derived from a common bone marrow stem cell that gives rise to a macrophage progenitor and a lymphoid stem cell. The macrophage progenitor then develops into a monocyte macrophage, and the lymphoid stem cell gives rise to a T-lymphocyte progenitor and a B-lymphocyte progenitor. The precursors of T-lymphocytes migrate to the thymus, where they "mature" and all types of T-lymphocytes are formed. "Maturation" of B-lymphocytes occurs in the bone marrow, where they become mature bone marrow B-lymphocytes. Under the influence of an antigen, they turn into plasma cells that synthesize specific antibodies against these antigens.
On the surface of T- and B-lymphocytes there are various receptors (protein structures), which are the antigens of these lymphocytes and in which different types of lymphocytes differ from each other. These antigens can recognize different types of lymphocytes, so they are called markers or SD antigens (international name).
By function and CD antigens, lymphocytes are divided into the following varieties or subpopulations.
T-helpers (CD4)- recognize the antigen, then stimulate the formation of plasma cells and the production of antibodies by them, activate macrophages (participate in humoral immune response).
T-killers or cytotoxic T-lymphocytes - CTL (SD8 and SD3) - recognize antigens and destroy target cells that carry antigens, tumor cells, cells infected with viruses, without the participation of antibodies and complement with the help of toxin enzymes (lymphotoxins) secreted by them (participate in cellular immune response).
T-suppressors (SD8) - reduce the activity of immunocompetent cells, thereby regulating the intensity of the immune response, participate in the formation of immunological tolerance.
T-inductors (SD4)- recognize the antigen and increase the activity of immunocompetent cells (helpers, suppressors, killers, macrophages), regulating the intensity of the immune response.
T-effectors of HRT(delayed type hypersensitivity) ( CD8) - participate in allergic reactions of a delayed (cellular) type, unlike CTLs, they do not have direct cytotoxicity, but destroy target cells indirectly (through other cells).
memory T cells- they retain the "memory" of the antigen for a long time, when this antigen enters the body again, they contribute to a faster and stronger immune response.
B-lymphocytes- participate in the formation of antibodies (humoral immunity), under the influence of an antigen they turn into plasma cells that form antibodies against this antigen (their markers - CD antigens - are these antibodies).
Memory B cells– as well as memory T-cells.
NK- cells (natural killers) (their antigens differ from T- and B-lymphocytes)- "kill" tumor and foreign cells, participate in the rejection of transplanted organs, do not have specificity.
Zero cells(do not have antigens of T- and B-cells) - immature forms of lymphocytes with cytotoxicity (capable of "killing" target cells).
Any form of immune response 3 types of cells interact: macrophages, T-lymphocytes and B-lymphocytes.
The humoral immune response is the production of immunoglobulins (specific antibodies). Doesn't participate macrophages, T-helpers and B-lymphocytes.
The main stages of the humoral immune response.
1) absorption of an antigen (for example, a microbial cell) by a macrophage, its digestion, "exposing" on its surface of undigested parts of the antigen (they retain foreignness) for their recognition by T- and B-lymphocytes;
2) recognition of the antigen by T-helper (protein part) upon direct contact with a macrophage;
3) recognition of the antigen by B-lymphocytes (determinant part) upon direct contact with a macrophage;
4) transmission of a non-specific activation signal to the B-lymphocyte through mediators (substances): the macrophage produces interleukin-1 (IL-1), which acts on the T-helper and induces it to synthesize and secrete interleukin-2 (IL-2), which acts on B-lymphocyte;
5) transformation of a B-lymphocyte into a plasma cell under the influence of IL-2 and after receiving information from a macrophage about the antigenic determinant;
6) synthesis by plasma cells of specific antibodies against an antigen that has entered the body and the release of these antibodies into the blood (antibodies will specifically bind to antigens and neutralize their effect on the body).
Thus, for a complete humoral response, B cells must receive 2 activation signals:
1) specific signal– information about the antigenic determinant that the B-cell receives from the macrophage;
2) non-specific signal- interleukin-2, which the B-cell receives from the T-helper.
Cellular immune response underlies antitumor, antiviral immunity and transplant rejection reactions, i.e. transplant immunity. Involved in cellular immune response macrophages, T-inducers and CTLs.
The main stages of the cellular immune response are the same as in the humoral response. The difference lies in the fact that T-inducers are involved instead of T-helpers, and CTLs are involved instead of B-lymphocytes. T-inducers activate CTL with the help of IL-2. Activated CTLs, when an antigen enters the body again, “recognize” this antigen on a microbial cell, bind to it, and only upon close contact with the target cell “kill” this cell. CTL makes protein perforin, which forms pores (holes) in the shell of a microbial cell, which leads to cell death.
Antibody formation in the human body occurs in several stages.
1. Latent phase- antigen recognition occurs during the interaction of macrophages, T- and B-lymphocytes and the transformation of B-lymphocytes into plasma cells, which begin to synthesize specific antibodies, but antibodies are not yet released into the blood.
2. logarithmic phase- antibodies are secreted by plasma cells into the lymph and blood, and their number gradually increases.
3. Stationary phase- the number of antibodies reaches a maximum.
4. Antibody Decreasing Phase – the number of antibodies gradually decreases.
During the primary immune response (the antigen enters the body for the first time), the latent phase lasts 3–5 days, the logarithmic phase lasts 7–15 days, the stationary phase lasts 15–30 days, and the decline phase lasts 1–6 months. and more. In the primary immune response, Ig M is synthesized first, and then Ig G, later Ig A.
With a secondary immune response (the antigen enters the body again), the duration of the phases changes: a shorter latent period (several hours - 1-2 days), a faster rise in antibodies in the blood to a higher level (3 times higher), a slower decrease antibody levels (over several years). In the secondary immune response, Ig G is immediately synthesized.
These differences between the primary and secondary immune response are explained by the fact that after the primary immune response, Memory B and T cells about this antigen. Memory cells produce receptors for this antigen, so they retain the ability to respond to this antigen. When it enters the body again, an immune response is formed more actively and quickly.
Allergy - it is hypersensitivity (hypersensitivity) to allergen antigens. When they enter the body again, damage to their own tissues occurs, which is based on immune reactions. Antigens that cause allergic reactions are called allergens. Distinguish exoallergens entering the body from the external environment, and endoallergens that form inside the body . Exoallergens are of infectious and non-infectious origin. Exoallergens of infectious origin are allergens of microorganisms, among them the most powerful allergens are allergens of fungi, bacteria, viruses. Among non-infectious allergens, household, epidermal (hair, dandruff, wool), medicinal (penicillin and other antibiotics), industrial (formalin, benzene), food, vegetable (pollen) allergens are distinguished. Endoallergens are formed during any impact on the body in the cells of the body itself.
Allergic reactions are of 2 types:
-immediate type hypersensitivity (ITH);
- delayed-type hypersensitivity (DTH).
GNT reactions appear 20-30 minutes after repeated exposure to the allergen. DTH reactions appear after 6-8 hours and later. The mechanisms of HNT and HRT are different. HIT is associated with the production of antibodies (humoral response), DTH - with cellular reactions (cellular response).
There are 3 types of GNT: I type – IgE - mediated reactions ; IItype – cytotoxic reactions ; IIItype – immune complex reactions .
ReactionsItype most often caused by exoallergens and associated with the production of IgE. When the allergen first enters the body, the formation of IgE occurs, which have cytotropism and bind to basophils and mast cells of the connective tissue. Accumulation of antibodies specific to the allergen called sensitization. After sensitization (accumulation of a sufficient amount of antibodies) with repeated exposure to the allergen that caused the formation of these antibodies, i.e. IgE, the allergen binds to IgE located on the surface of mast and other cells. As a result, these cells are destroyed and special substances are released from them - mediators(histamine, serotonin, heparin). Mediators act on the smooth muscles of the intestines, bronchi, bladder (cause it to contract), blood vessels (increase the permeability of the walls), etc. These changes are accompanied by certain clinical manifestations (painful conditions): anaphylactic shock, atopic diseases - bronchial asthma, rhinitis, dermatitis , childhood eczema, food and drug allergies. In anaphylactic shock, shortness of breath, choking, weakness, restlessness, convulsions, involuntary urination and defecation are observed.
To prevent anaphylactic shock, desensitization to reduce the amount of antibodies in the body. To do this, small doses of the antigen-allergen are introduced, which bind and remove part of the antibodies from the circulation. For the first time, the desensitization method was proposed by the Russian scientist A. Bezredka, therefore it is called the Bezredka method. To do this, a person who previously received an antigenic preparation (vaccine, serum, antibiotics), when it is re-administered, is first injected with a small dose (0.01 - 0.1 ml), and after 1 - 1.5 hours - the main dose.
ReactionsIItype are caused by endoallergens and are caused by the formation of antibodies to the surface structures of their own blood cells and tissues (liver, kidneys, heart, brain). These reactions involve IgG, to a lesser extent IgM. The resulting antibodies bind to the components of their own cells. As a result of the formation of antigen-antibody complexes, complement is activated, which leads to the lysis of target cells, in this case cells of one's own body. Allergic lesions of the heart, liver, lungs, brain, skin, etc.
ReactionsIIItype are associated with long-term circulation of immune complexes in the blood, i.e. antigen-antibody complexes. They are caused by endo- and exoallergens. They involve IgG and IgM. Normally, immune complexes are destroyed by phagocytes. Under certain conditions (for example, a defect in the phagocytic system), immune complexes are not destroyed, accumulate and circulate in the blood for a long time. These complexes are deposited on the walls of blood vessels and other organs and tissues. These complexes activate complement, which destroys the walls of blood vessels, organs and tissues. As a result, various diseases develop. These include serum sickness, rheumatoid arthritis, systemic lupus erythematosus, collagenosis, etc.
Serum sickness occurs with a single parenteral administration of large doses of serum and other protein preparations 10–15 days after administration. By this time, antibodies to the proteins of the serum preparation are formed and antigen-antibody complexes are formed. Serum sickness manifests itself in the form of edema of the skin and mucous membranes, fever, swelling of the joints, rash, itching of the skin. Prevention of serum sickness is carried out according to the Bezredke method.
ReactionsIVtype - delayed hypersensitivity. These reactions are based on the cellular immune response. They develop in 24 to 48 hours. The mechanism of these reactions is the accumulation (sensitization) of specific T-helpers under the influence of the antigen. T-helpers secrete IL-2, which activates macrophages, and they destroy the antigen-allergen. Allergens are pathogens of some infections (tuberculosis, brucellosis, tularemia), haptens and some proteins. Type IV reactions develop in tuberculosis, brucellosis, tularemia, anthrax, etc. Clinically, they manifest themselves as inflammation at the site of allergen injection during tuberculin reaction, as delayed protein allergy and contact allergy.
tuberculin reaction occurs 5-6 hours after intradermal administration of tuberculin and reaches a maximum after 24-48 hours. This reaction is expressed in the form of redness, swelling and compaction at the injection site of tuberculin. This reaction is used to diagnose tuberculosis and is called allergic test. The same allergy tests with other allergens are used to diagnose diseases such as brucellosis, anthrax, tularemia, etc.
delayed allergy develops with sensitization by small doses of protein antigens. The reaction occurs after 5 days and lasts 2-3 weeks.
contact allergy develops under the action of low molecular weight organic and inorganic substances that combine with proteins in the body. It occurs with prolonged contact with chemicals: pharmaceuticals, paints, cosmetics. It manifests itself in the form of dermatitis - lesions of the surface layers of the skin.
Allergic antibodies are a large group of globulins in the blood of humans and animals. The most important difference between antibodies and "normal" globulins is their immunological specificity and biological ability to cause certain allergic reactions.
Many immune antibodies have properties of allergic antibodies. So, for example, antitoxins to bacterial exotoxins are involved in the mechanism of anaphylactic shock caused by these toxins (“toxin anaphylaxis” according to I.V. Morgunov, 1963, etc.), lysines and complement-binding antibodies cause allergic reactions of the “reverse type”, allergic “ cytotoxic shock and various allergic reactions of cytolysis (Forssman, 1911; Waksman, 1962).
An extensive group of allergic reactions is caused by antibodies such as precipitate types and agglutinins; Arthus phenomenon, Overy phenomenon, rabbit anaphylactic shock, serum sickness, drug allergy (Artlius, 1903; Pirquet, 1907; Ovary, 1958). Among the antibodies of this group, such types of propicitypes and agglutinins are also involved in the mechanism of allergic reactions, which were not detected by the usual methods known in the old immunology of ring-recipitation, direct macro- and microagglutination, etc. These antibodies were found in the blood of people with serum sickness or animals with anaphylactic sensitization after removal of precipitins from the blood by a specific antigen. The blood serum after the removal of precipitins retained the ability to passively transmit the state of general or local anaphylaxis. Richefc (1907) and then Friedberger (1909) called these antibodies anaphylactic.
Later, when studying a number of forms of allergic diseases (hay fever, "atopic" diseases, immunohematological diseases), special types of allergic antibodies were identified. Some of them revealed the properties of precipitins or agglutinins only under special conditions or a special technique for their detection (co-precipitation reaction, agglutination of erythrocytes previously treated with tannin, etc.). These allergic antibodies are known as "incomplete" ("incomplete"), allergic cold agglutinins, etc.
This group of allergic antibodies occupies, as it were, an intermediate position between full-fledged precipitates and agglutinins and a group of allergic antibodies that cause sensitization of the skin of a healthy person after the introduction of the blood serum of a sick pollino into it.
or another type of immediate (chimergic) allergy "type (allergies to fungal, dust, food and other allergens). Sosa (1925) called the last type of antibodies "reagins" or "atotopes" (the latter name did not take root). Biological and physical -chemical properties of reagins differ significantly from those of all known immune antibodies.
Absolutely peculiar antibodies involved in the mechanism of delayed-type allergic reactions and some immediate allergic reactions are the so-called tissue, or cellular, fixed, “sessile” antibodies. The properties and mechanism of action of these antibodies have not yet been studied enough. Thus, many types of antibodies take part in the mechanisms of various allergic reactions, ranging from antibodies with biological and physico-chemical properties of immune to special types of antibodies that have nothing to do with antibodies that cause immune reactions.
All allergic antibodies can be divided into two large groups. The first group includes antibodies of the blood and other biological fluids (humoral antibodies), the second group - antibodies that sit on cells - tissue, fixed or "susceptible" (cellular antibodies). The last group of antibodies should not be confused with humoral antibodies, secondarily fixed on smooth muscle cells, on other tissues in case of passive anaphylaxis and immediate type allergies (Schultz-Dale reaction, passive skin anaphylaxis - Overy phenomenon, passive anaphylactic shock, etc.).
The relationship between different types of allergic antibodies can be represented as the following scheme (Scheme 7).
Scheme 7
RELATIONSHIP OF DIFFERENT TYPES OF ALLERGIC ANTIBODIES Allergic antibodies
"Free Fixed (cellular)
Prodipti n ing
Skin-seislbilizing blocking (protective antibodies)
(reagins)
Biological and physico-chemical properties of normal and immune globulins in human and animal blood serum are in the center of attention of modern biochemists and immunologists.
The view of antibodies, including allergic ones, as altered blood globulins was developed in our country by V. A. Barykin (1927), N. F. Gamaleya (1928) in the form of a doctrine of immunity as a function of the colloidal state of blood proteins (V. A. Barykip) or Li in the form of the imprint theory (N. F. Gamaleya), subsequently developed by Pauling and Haurowitz and many other immunologists.
Humoral allergic antibodies, together with immune antibodies, are a large family of globulins that have acquired the ability to specifically bind to a wide variety of allergens,
causing their formation or having determinant groups in common with them. According to Grabar (1963), antibodies, both immune and allergic, physiologically express the transport function of blood globulins to the same extent as it is known for the transport of carbohydrates (glycoproteins), lipoids (lipoproteins) and other substances by globulins. Obviously, in the case of antibodies, this transport function simultaneously acquires a high degree of immunological specificity, which provides antibodies with their protective or aggressive effects.
The specificity of some allergic antibodies is relative. When rabbits are sensitized by one type of plant pollen, antibodies to many types of pollen allergens arise (AD Ldo et al., 1963). In the clinic of polliposis, polyvalent sensitivity to many types of tree and grass pollen is usually observed. In serum sickness, rheumatism, antibodies are observed that agglutinate and lyse sheep erythrocytes (heterophilic Forsman antibodies), as well as precipitation to blood proteins of many mammalian species (rabbit, cat, dog, rat, mouse, etc.).
Cooke and Sherman (1940) in the passive transfer reaction showed that allergic antibodies can react with many allergens. When a rabbit is immunized with ram blood serum, precipitatetypes are also formed for human, horse, and pig blood proteins (Landsteiner and van Slicer, 1939, 1940).