IMMUNITY (Latin immunitas release, disposal of something) — immunity of an organism to the infectious and noninfectious agents and substances having alien antigenic properties.
For a long time under And. understood immunity of an organism to infectious diseases. Also I. I. Mechnikov (1903) who wrote held such opinion: «To infectious diseases it is necessary to understand the general system of the phenomena thanks to which the organism can maintain attack of disease-producing microbes as immunity».
Further the concept «immunity» received broader interpretation and began to include a condition of immunity of an organism not only to microbes, but also to other pathogenic agents, napr, to helminths, and also to various alien antigenic substances of an animal or plant origin.
Immune responses have protective, adaptive character and are directed to release of an organism from the alien antigens coming to it from the outside and breaking constancy of its internal environment. These reactions participate also in elimination of the antigens which are formed in an organism under action biol and physical. - chemical factors: bacteria, viruses, enzymes, medicinal and other chemical drugs, radiation.
Oncogenous viruses, carcinogenic substances can induce in cells products of new antigens in response to which emergence the organism answers with the cellular and humoral immune responses directed to elimination of these antigens, and together with them and cells of tumors (see. atrepsy ).
Immune responses arise also on incompatible isoantigens (alloantigens) which can come to an organism at hemotransfusion, organ transplantation and fabrics, and also in the course of inogruppny pregnancy (see. Blood groups , Immunity transplant , Rhesus factor ).
Immune responses, protective by the nature, owing to these or those reasons can be perverted and directed not only to alien antigens that is natural, but also on some own, normal, not changed antigens of cells and fabrics therefore there are true autoimmune diseases. Immune responses can be the cause of hypersensitivity of an organism to alien antigens — phenomena allergies (see) and anaphylaxis (see).
Studying molecular, cellular and obshchefiziol. the reactions providing immunity of an organism to infectious agents makes the main maintenance of science about And.
- 1 Ontogenesis and phylogeny of defense immune responses
- 2 Types of immunity
- 3 Factors and mechanisms of hereditary immunity
- 4 Factors and mechanisms of artificial immunity
- 6 Immunity at parasitic diseases
- 7 Features of immunity at children
Ontogenesis and phylogeny of defense immune responses
Defense immune responses developed in the course of long organic evolution, they formed and improved in close interaction of an organism with various antigenic factors. Among them microbes won and win first place. Different types of animals owing to the genetic features, and also features of their interaction with environmental factors developed nonspecific and specific reactions inherent in each look. The last were improved and became complicated in the course of phylogenesis. With priming defense reaction from microbes at all living beings, beginning from protozoa, is phagocytosis (see). To phagocytosis of amoebas performs double function — food and protection. At sponges the differentiation of phagocytes on the cells bearing function of food (entodermalny phagocytes), and the cells performing function of protection (mesodermal phagocytes) is planned already. At more high-organized metaphytes differentiation of function of these cells gained further development. In addition to the englobing cells, there were cells capable to specifically distinguish alien antigens (see), and the cells capable to develop antibodies (see). Close interaction between these cells, and also their interaction with humoral substances and others obshchefiziol is established. factors and systems of an organism. The harmonious and interconnected system of cellular and humoral protection of an organism against the microbes and other alien antigenic substances getting into an organism develops. The new protective mechanism — antibody formation — is rather late acquisition of fauna. This mechanism is absent at invertebrates and some primitive fishes. They have no organized adenoid tissue, products of the proteins similar to immunoglobulins are not observed. For the first time the specific immune response, though slight, is noted at lampreys. The rudimentary thymus gland is found in them, and antibodies are formed only to a nek-eye to antigens and belong to the class IgM. The last are initially arisen immunoglobulins (see). Antibody formation at cartilaginous fishes, napr, at sharks whose thymus gland is already more developed is more effectively shown, and in a spleen also plasmocytes — producers of immunoglobulins meet. At cartilaginous and bony fishes, unlike more high-organized vertebrata, plasmocytes synthesize hl. obr. IgM. At amphibians and reptiles already two classes of immunoglobulins — IgM and IgG reminding IgM and IgG of mammals accurately come to light. Products of these immunoglobulins at them are still poorly developed and depend on surrounding temperature. Immune processes at birds are more perfect. Except IgM and IgG, their IgA are found also. The bursa of Fabricius at birds, in addition to a thymus gland, serves as the place of formation of immunocompetent cells, in it there is a differentiation of stem cells in B-lymphocytes. It exercises control of development of the germinal centers in a spleen and the mechanism of synthesis of immunoglobulins plasmocytes. At mammals, in addition to a thymus gland, the same function as a bursa of Fabricius at birds, is carried out, apparently, by an adenoid tissue of peyerovy plaques and an appendix. Immunol, memory at birds is well developed. They are capable to answer quickly with specific reaction to secondary administration of the same antigen and to form antibodies in a high caption. Function of antibodyformation at mammals is represented to even more perfect. At dogs, pigs, cows, horses, rabbits, Guinea pigs, rats, mice three main classes of immunoglobulins are found: IgM, IgG, IgA, and in many cases and IgE. IgD, besides, are found in the person.
Emergence and development of immune responses in ontogenesis as if repeats in a short form their phylogenesis. Gradual formation, differentiation and maturing of an adenoid tissue, change of synthesis of one immunoglobulins by others is here too observed. At the person as well as at other mammals, before everything the plasmocytes producing immunoglobulins of a class M (macroglobulins), and later the immunocytes synthesizing antibodies of the class G and A begin to function. According to it macroglobulins are found, sometimes in a low caption, and in a fruit. Synthesis of IgM, IgG and IgA begins soon after the birth, however the content of these proteins in blood serum at children up to 3 — 5 years does not reach a level more of adults. IgD and IgE appear on the second year of life of the child and reach the level of adults by 10 — 15 years.
Similar process of the sequence of products of immunoglobulins of various classes is observed also in experimental conditions, and also at an infection or immunization of the person.
Whether one clone of plasmocytes produces all classes of immunoglobulins or each class of immunoglobulins is synthesized only by a certain clone of immunocytes, remains still insufficiently studied.
Types of immunity
Depending on the mechanisms creating immunity of an organism to pathogenic agents distinguish two main types And. — hereditary and acquired.
Hereditary immunity (synonym: inborn, specific, natural, constitutional) it is inherent in this or that species of an animal or the person and passes by inheritance from father to son, as well as other genetic signs. As examples specific And. it is possible to lead immunity of animals to a virus of chicken pox of the person, viruses of infectious and serumal hepatitis. It is not possible to cause a disease of a virus of measles in many animals. People are unreceptive to such viral infections of animals as plague of a cattle, dogs. Rats and mice are steady against diphtheritic toxin, and rabbits, cats and dogs — to tetanic. Monkeys a Rhesus factor are unreceptive to the activator of a tetrian fever. There are various degrees of tension specific And. — from absolute resistance of an animal to any microbe that is observed seldom, to relative immunity, edge can be overcome by means of various influences. Absolute resistance of a rabbit to an influenza virus does not manage to be overcome introduction of huge doses pathogenic for the person or mice of a virus. Specific And. it is not possible to overcome sometimes easing of the general resistance of an organism: radiation, processing by a hydrocortisone, blockade of cells of reticuloendothelial system, a splenectomy, keeping of animals on a hungry diet. Relative natural immunity to a certain species of a microbe can be and is overcome. Classical experience of L is known. Pasteur on infection of hens, unreceptive to a malignant anthrax, by artificial decrease in body temperature at them. At frogs fervescence does them susceptible to tetanus.
Specific And. to a certain species of a microbe it is genetically determined. As Seybin showed (A. Sabin, 1952), the rock Feller line of mice (PRI) had 100% resistance to a virus of yellow fever (a strain 17 D), unlike the line of mice of Swiss at whom incidence was observed by 100%. The gene of a sickemia coding synthesis of the hemoglobin differing from usual only in replacement of one amino acid another does erythrocytes of these persons steady against plasmodiums of malaria. Animal, naturally unreceptive to one species of a microbe, there can be vysokovospriimchiva to another. E.g., mice, viruse-resistant St. Louis, are sensitive to viruses of vesicular stomatitis, rage, a lymphocytic choriomeningitis, i.e. specific And. — this state characterizing immunity only to strictly certain species of a microbe. There are also intraspecific or racial distinctions in a susceptibility to infectious diseases. E.g., midday sandworts from the enzootichny centers of plague are many times steadier against this infection, than the sandworts caught from places where there are no natural centers of plague. Apparently, natural resistance of these animals was result of continuous contact them with the causative agent of plague. In the course of natural selection there were versions steady against an infection. The Algerian sheep are steadier against a malignant anthrax, than European that also characterizes racial And.
Artificial immunity can develop as a result of the postponed infection or immunizations (see). Acquired And., unlike specific, it is not descended. One of key features acquired And. — its strict specificity. Distinguish actively and
the artificial immunity which is passively acquired by I. Aktivno can result from the postponed clinically expressed disease and as a result of latent infection (natural actively acquired And.), and also it can be received by vaccination by live or inactivated vaccines (artificially acquired And.).
Actively acquired And. is established not at once — in 1 — 2 week or later and remains rather long — years or decades. E.g., after transferring of measles, yellow fever remains lifelong And. At other viral infections, napr, at flu, actively acquired And. keeps rather not for long — within 1 — 2 years.
Passively artificial immunity arises at a fruit because he receives antibodies from mother through a placenta therefore newborns during certain time remain unreceptive to a nek-eye to infections, napr, to measles. Passively acquired And. it can be created and it is artificial, by introduction to an organism of the immunoglobulins received from actively immunizirovanny people or animals. Passively acquired And. is established quickly — in several hours after administration of immune serum or immunoglobulin and short time — during 3 — 4 weeks remains. The organism is exempted from antibodies of heterological serums even quicker — in 1 — 2 week therefore And., caused by them, is less long.
Depending on the result of infectious process distinguish two forms acquired And. — sterile and unsterile (infectious).
Sterile immunity is followed by liberation from the infectious agent, and the last does not manage to be allocated after transferring of an infection. However sometimes an organism, gaining immunity, becomes the carrier, for bigger or smaller term, a microbe, pathogenic for susceptible people. Defense reactions not always are sufficient for full elimination of the activator of an organism.
A peculiar form acquired And. the immunity for the first time described by R. Koch in 1891 is infectious, or unsterile. It is caused by presence of the infectious agent in an organism and proceeds until microbes in it remain. Between defense reactions and activity of pathogenic microbes a peculiar unstable equilibrium is established. Existence of a tuberculous focus in an organism tells him immunity to new infection with tuberculosis. The similar phenomenon observed also Yu. Morgenrot (1920): the caused in mice hron, streptococcal infection reported resistance to repeated infection with a dose of this microbe, deadly to control animals. Feature unsterile And. its functioning only in the presence of the infectious center is. Removal of the last is followed by I. Dokazan's loss an opportunity long, and sometimes and a lifelong persistention of viruses at the genetic level, i.e. inclusion of DNA or DNA transcripts of some viruses in genomes of cells. This peculiar form of existence of a virus and a cell finds the expression and in immune responses of an organism both on virus, and on virusindutsirovanny antigens that can be also considered as one of forms of an immunitas non sterilisans.
Noting a basic difference in an origin specific and acquired And., it must be kept in mind that both of these forms of immunity are inseparably linked.
Acquired And. forms on the basis of hereditarily the determined factors and mechanisms. Immunoreactive genes (MESPILUSES) define potentiality of reaction to this or that antigen and force of an immune response. A basis both hereditary, and acquired And. make molecular, cellular and obshchefiziol. reactions of an organism to alien antigens.
As a result of genetic features or under the influence of diverse external impacts on an organism cellular or humoral immune responses can be to a greater or lesser extent weakened or changed that can become the reason various immunodeficient and immunopatol. states (see. Immunological insufficiency , Immunopathology ).
Specific And., as well as acquired, changes depending on age. At some animal species newborns are not capable to synthesis of immunoglobulins. Newborn animals are, as a rule, more susceptible to a virus, than adults. E.g., it is easy to cause infection with viruses of Koksaki in mice suckers, it is not possible to cause a disease of these viruses in adult mice. Influenza viruses well develop in chicken embryos, but at chickens of development of an infection does not occur. Newborn Guinea pigs and white rats are susceptible to a virus of a tick-borne encephalitis, in an organism of mature animals this virus does not breed. Ability of an organism to localize an infection is more expressed at adults, than at children at whom it is more often observed dissiminations of microbes and generalization of process. At young animals visible inflammatory reactions are less expressed, than at adults.
Factors and mechanisms of hereditary immunity
Specific And., as well as acquired, is defined by two major factors: features of defense reactions of a macroorganism and nature of a microbe, its virulence and toksigennostyo.
Specific And. in relation to a certain species of a microbe depends not only on a high tension of defense reactions of an organism, but also on inability of a microbe to parasitizing in it. The factors and mechanisms providing specific And., are very various.
Areactivity of cells — one of factors specific And. At the heart of antiviral specific And. lack of the cells, sensitive to a virus, capable to support its reproduction lies.
Areactivity of cells as many researchers believe, is caused by lack of virus receptors on a surface of cells therefore viruses cannot be adsorbed on cells and, therefore, get into them. As showed Holland's researches, to Mac-Larena (J. J. Holland, L. Page of McLaren, 1952), etc., sensitivity of cultures of cells of primacies to poliomyelitis viruses depends on existence at them the corresponding receptors, and lack of the last in cells of not primacies defines their resistance to poliomyelitis viruses. Confirmation to it were experiments on infection of resistant cells of culture of the RNA fabric emitted from a poliomyelitis virus of the I type. RNA, free from protein, has ability to get into cells, resistant to a poliomyelitis virus, and to cause in them a reproduction of a virus. Similar results are received also in experiences of in vivo. White mice, naturally resistant to a poliomyelitis virus of the I type, got sick at intraspinal introduction of a RNA virus by it. It is supposed that resistance of mice to this virus depends on lack of receptors for a virus on membranes of cells of c. N of page.
Susceptible cells of culture of fabric adsorb 90% of a virus of poliomyelitis, and resistant — less than 10%.
There is a certain dependence and between ability of tissues of lung to adsorb an influenza virus and degree of a susceptibility of animals to a disease of flu. Tissues of easy African polecats and the person high-susceptible to flu, have the greatest adsorptive activity. Tissues of lungs of a rabbit — an animal, unreceptive to flu, do not adsorb a virus. The inactivation of receptors of cells of a chicken embryo a receptor the destroying enzyme reduces a susceptibility of cells to an influenza virus. Thus, existence of virus receptors at sensory cells — one of the first and necessary conditions for infection; in the absence of virus receptors the cell is impregnable under natural conditions infections with its virus. However specific antiviral And. hardly it is possible to explain only with absence in cells of virus receptors. Guinea pig of a rezistentn to an influenza virus though cells of its fabrics can adsorb a virus, i.e. have the corresponding receptors on a surface of cells. It is necessary to recognize, apparently, existence as well other factors and mechanisms which are directly involved in formation of natural resistance to viruses. In formation natural And. to a viral infection the leading place is taken, apparently, by cells which stability is genetically determined. However and other factors of an organism play a part in natural resistance to viruses. So, there is not always a compliance between resistance of an animal to a viral infection and resistance of his cells to a virus. To a virus of measles, e.g., sensory cells of chicken fibroblasts, cells of a kidney of a Guinea pig, a rabbit; however it is not possible to cause an experimental clumsy infection in these animals. The virus of a tick-borne encephalitis is reproduced in primary cultures of cells of a kidney of a rabbit — an animal, unreceptive to this infection. The person is unreceptive to a virus of classical plague of birds though this virus breeds in cultures of tissue of lungs of an embryo of the person. Apparently, in an organism of resistant animals there is other relationship between a virus and a cell, than in cultures of fabrics.
Inborn And. to toxins it is caused by absence in cells of the receptors capable to fix toksinony E.g., at rats, immune to diphtheritic toxin, the last is not adsorbed by cells of bodies and brought out of an organism without change. Natural immunity to toxins can be shown also in those cases if the receptors having affinity to toxin are localized in bodies or fabrics on which toxin has no harmful effect. E.g., at a scorpion the tetanin is fixed by cells of a liver which do not suffer from it. At a cayman, unreceptive to a tetanin, the last also communicates cells which are steady against it. Chicken perishes from a tetanin if it is entered directly under a meninx, and does not get sick at its introduction to blood as toxin before receipt in c. the N of page is intercepted by cells on which it has no effect.
Normally functioning skin and mucous membranes make the first line of protection of an organism against bacterial and viral infections. Constantly exfoliated epithelium of skin serves as reliable protection against an infection, and only damage of integuments opens ways for penetration of disease-producing agents in an organism. Skin, however, not only mechanical protection. Allocations of sweat and sebaceous glands contain the substances which are perniciously operating on a bacterium of a typhoid, a paratyphoid, colibacillus, etc. Bactericidal properties of skin depend on contents in separated sweat and sebaceous glands milk and fat to - t. Fat to - you and the soaps which are contained in radio and alcoholic extracts of skin show bactericidal action concerning bacteria of intestinal group, diphtheria, a streptococcus.
Acid contents of a stomach — Wednesday, in a cut many microbes sensitive getting with food and water to - those, napr, a cholera vibrio are inactivated.
The mucous membranes covered by a flat epithelium are a zna a chitelny barrier against penetration of microbes. It is promoted as well secrets of mucous glands. They not only mechanically delete microbes from a surface of cells, but also neutralize them. The cylindrical epithelium covering mucous membranes of a respiratory path is supplied with cilia thanks to what there is a mechanical removal them from an organism of foreign substrates, including and microbes.
In separated mucous membranes the lysozyme (atsetilmuramidaza) — the main protein consisting of one polypeptide chain and functioning as mucolytic enzyme contains. It chips off from mukopeptidny (peptidoglikanovy) complexes of a bacterial wall N-acetyl a glycosamine and N-atse-tilmuramovuyu to - that. As a result the wall of bacteria collapses, there is its lysis. Micrococci, sartsina are most sensitive to a lysozyme. Death of bacteria under the influence of a lysozyme can happen also without their dissolution. Lysozyme (see) contains in many fabrics and liquids. In quite high concentration it is in macrophages of lungs, secrets of a conjunctiva, a nose, slime of intestines, saliva. The lysozyme can interact with IgA and cause a lysis of bacteria, resistant to a lysozyme. The lysozyme does not affect viruses. Mucous membranes of a conjunctiva, cornea, an oral cavity, a nose, a throat are in constant contact with a huge number of bacteria, including stafilokokk, pneumococci, etc. However the diseases connected with damage of these mucous membranes bacteria are observed rather seldom. Apparently, the liquids which are constantly washing mucous membranes, and the lysozyme which is contained in them, and also secretory antibodies are one of mechanisms of protection. Normal fabrics contain various inhibitors of enzymatic activity of bacteria. Those are inhibitors of hyaluronidase, a lecithinase, collagenase, phospholipase, sialidoses, fibrinolysin. Important factor natural And. are and inhibitors of viruses (see), capable to interact with viruses and to suppress their activity. Inhibitors to influenza viruses, a parainfluenza, parotitis, a tick-borne encephalitis, poliomyelitis, etc. are found in serums of the person and animals. At one animal species inhibitors are characterized by high activity in relation to certain viruses, at others — this activity is expressed more weakly. E.g., inhibitors of saliva of dogs — animals, naturally unreceptive to flu pu, have the ability which is the most expressed in comparison with saliva of the person to suppress viability of an influenza virus. The mechanism of effect of inhibitors is similar to action of antibodies: entering interaction with a virus, inhibitors, as well as antibodies, its adsorptions on a surface of a sensory cell and ability to get into it interfere. Inhibitors, as well as antibodies, carry out function of neutralization of a virus on the way to a sensory cell. Depending on an infection or immunization the content of inhibitors can change. At the beginning of a viral infection or immunization in the fabrics which are directly interacting with an influenza virus there is a reduction of amount of inhibitors, and then their substantial increase. On 11 — the 16th day after infection the amount of inhibitors by 5 — 8 times surpasses their level in easy control mice, and then their gradual falling to norm is observed. Credits of inhibitors of viruses in saliva, as a rule, do not remain constants with healthy people and are subject defined fiziol. to the fluctuations which are not depending on seasonal influences.
At patients with a severe form of flu big changes of a caption of inhibitors in comparison with healthy are noted considerably. At height of development of an influenzal infection almost at a half of the inspected patients virus inhibitors in saliva were absent or were defined in a low caption.
To number of natural (inborn) factors And. belongs and properdin (see) — the protein of normal serum having bactericidal properties. In the presence of a complement or its separate components and ions of magnesium properdin has bactericidal effect on gram-positive and gram-negative bacteria and inactivates viruses. Contents a proper the dyne at various animals unequally, is richest with it serum of rats. Effect of properdin, as well as a lysozyme, is not specific. The question of the nature of properdin and its relation to a complement remains still insufficiently found out.
To number of nonspecific humoral factors antimicrobic And. leukins and a beta lysine belong.
Leukins thermostable (maintaining heating to t ° 75 °) — the antibacterial agents which are released from leukocytes at their destruction. The leukins received from different types of animals are not identical on the bactericidal activity and an orientation of their action in relation to various microbes. The substances, similar to leukins, extracted from thrombocytes received the name of plakin. Thermostable (inactivated at t ° 63 — 70 °) the bactericidal factor is found by another in serums of animals and called a beta lysine. The beta lysine inactivated by heating can be recovered by addition of a small amount of fresh normal serum. Like leukin, the maintenance of a beta lysine in serum does not increase at immunization. Activity of a beta lysine is higher, than leukin, concerning stafilokokk and anaerobe bacterias. Such nonspecific factors of blood as for the second time are involved in immune responses C-reactive protein (see) and conglutinin. Their value in And. remains still insufficiently clear.
Important factor natural And. the complement — a complex system of the serum proteins having enzymatic properties is. The complement consists of various components (see. Complement ). Under natural conditions the components making a complement are inert, however at formation of a complex antigen — an antibody the system of a complement is activated. Education by a complex antigen — an antibody of a lattice promotes complement activation. One molecule IgM or two molecules IgG enough in order that process of activation began. If the antibody and antigen are not in equivalent quantities (e.g., excess of antigen takes place), then the lattice structure is not formed and the complement joins to a lesser extent. The monovalent antibodies which are not forming a lattice do not activate a complement. Antigen, connecting to a molecule of an antibody, changes its Fc the site therefore C1q a component, and then and C1r and C1s strongly joins the last. Ions of Ca are necessary for this interaction. The C1s component — pro-esterase after accession to the C1q and C1r components turns into active esterase, edges is necessary for functioning of other components of a complement. The formed complex changes the C4 component therefore the last joins a surface of a cell or a complex antigen — an antibody, and the C2 component also joins it. Ions of magnesium are necessary for this process. The following in chain reaction involves the SZ component, after disintegration to-rogo on fragments of C3a and C3b the last joins a cellular membrane. The formed new complex possesses several important biol, properties, he promotes phagocytosis, participates in reaction of immunosticking (see. Immune sticking ) and conglutinations (see), it is significantly important for a lysis. However only accession of the C5, C6, C7, C8 and C9 components reports to a complement ability to cause irreversible damages of a cell membrane. In cell membranes openings to dia appear. 10 nanometers therefore in a cell there can be it small molecules. There is a disorganization of structure and function, including and lysosomes of a cell, and her death.
Gram-negative bacteria are inactivated and digested enzymes of lysosomes. The complement completes immune responses, makes a lysis of microbes (bacteria, spirochetes, trypanosomes), activates development of inflammatory reaction, promotes phagocytosis and intracellular digestion.
In the course of phylogenesis the complement appeared along with immunoglobulins. The antibodies received from birds do not fix a complement of mammals. E.g., the immune serum received from hens does not activate a complement from rabbits, Guinea pigs or mice.
To natural factors And. also so-called normal antibodies which emergence, apparently, is not connected with the previous immunization or transferring of a disease belong. Normal antibodies are found in serums of the person and animals in relation to various bacteria: staphylococcus, to causative agents of a typhoid, dysentery, malignant anthrax, cholera, etc. A caption of normal antibodies, unlike immune, below, and an avidnost (see. Aviditet ) them it is expressed more weakly. Specificity of normal antibodies does not differ from immune antibodys and can be very high. Normal antibodies as well as immune, contact antigens (e.g., bacteria), cause their agglutination and a lysis in the presence of a complement, opsonize them, promote phagocytosis, neutralize toxins, viruses.
Normal antibodies, thus, perform function of natural protection of an organism against the microbes which got into it and other pathogenic agents having alien antigenic properties. Young animal normal antibodies have less, than at adults, and at fruits and newborns they often are absent. In addition to antibodies to microbes, blood serum of the person contains normal heteroantibodies to erythrocytes of a rabbit, rat, pig, ram, etc., and also isoantibodies anti-And yes anti-In to erythrocytes of the person.
Origins of normal antibodies remain not found out yet. There are two hypotheses of their origin. According to the hypothesis offered by L. Girshfeld (1928), normal isoantibodies arise in an organism irrespective of processes of immunization. Ability of cells to develop normal isoantibodies is defined by genetic signs. Phylogenesis of these signs and their ontogenetic development submit to the same laws, as development of anatomic signs. By analogy with a morphogenesis L. Girshfeld entered the concept «serogenez». Along with morfol, a differentiation in an organism occurs and serol, the differentiation, edges depends on age. Formation of normal antibodies as L. Girshfeld assumed, represents the «spontaneous», not depending on antigen function of the ripening and developing cells. Emergence of antibodies to diphtheritic toxin at inhabitants where diseases of diphtheria usually do not meet is an example of it, however anti-toxic antibodies reach the level of adults by 17 years.
Noting the genetic nature of an origin of normal antibodies, L. Girshfeld at the same time suggested that normal antibodies resulted from «long history of sufferings of mankind from infectious diseases», i.e. close and long contact of the person with the environment. The immune responses promoting survival of a look in the course of phylogenesis were fixed by selection and were descended. Further cells of an organism gained ability to develop antibodies irrespective of contact with antigen. This ability began to depend only on genetic features of the cells forming antibodies.
Other hypothesis is developed by A. Winer (1951) who considers that all normal antibodies result from imperceptible immunization. Antibacterial antibodies appear as a result of an asymptomatic infection while natural isohemagglutinins result from immunization of the person the heterogeneous antigens similar to antigens A and B of the person. These substances occur at many bacteria, zooparasites, some plants. Further development of these hypotheses were G. F. Springer's researches with sotr. (1959). According to G. F. Springer, only the device producing antibodies is inherited, and for its functioning the exogenous antigenic irritant, as well as is necessary for products of other antibodies. Thus, normal antibodies, according to this hypothesis, are formed as well as immune, i.e. as a result of immunization, and are the response to receipt in an organism of alien antigens.
To number of natural factors And. belongs and interferon (see), open Ayzeksom and Lindenmann (A. Isaaks, J. Lindenmann, 1957). It was known that one infection can slow down development another. E.g., the vaccine against smallpox did not take root at children within 9 — 15 days after inoculation to them a live clumsy vaccine. The inoculation of a live vaccine against poliomyelitis creates short-term And. to flu. The inhibiting effect of one viruses on development of others received the name of an interference phenomenon. This phenomenon as the mentioned authors showed, depends on the special protein produced by the infected cells — interferon.
Interferon leads to restriction of number of susceptible cells owing to what the infection stops. Explain these rather bystry stopping of flu and other acute viral infections, approach of bystry recovery. The greatest efficiency of interferon is shown at its preventive use. It is noted, however, and to lay down. effect of interferon at some viral infections.
The interference phenomenon takes place not only between viruses, but also between bacteria and other microbes.
It is known that normal flora of intestines can have antagonistic effect on some pathogenic bacteriums. E.g., colibacillus is an antagonist of a streptococcus, staphylococcus, causative agents of a typhoid and dysentery. Some bacteria produce the antibacterial agents operating on other bacteria that promotes resistance of an organism concerning pathogenic microbes. Use of antibiotics or radiation can lead to change of structure of normal flora and loss of evolutionarily developed protective function of an organism by it concerning accidentally arriving pathogenic agents.
To number of the major defense reactions of an organism important in hereditary and acquired And., the inflammation and phagocytosis belong. Microbes at the place of implementation begin to breed, produce the substances, toxic, alien for an organism, causing damage to cells. In the form of response defense reaction from an organism around the got microbes the local inflammatory center is formed (see. Inflammation ). Through the changed walls of capillaries polymorphonuclear granulocytes get here. In the inflammatory center temperature increases, there are an acidosis and a hypoxia which are perniciously operating on viruses. The inactivation of microbes is promoted by the normal and immune antibodys getting from blood, a complement, opsonins, a lysozyme, leukins, beta lysines, virus inhibitors. Leukocytes form the peculiar shaft interfering distribution of microbes. It is promoted also by obstruction of intercellular spaces fibrin. Phagocytal activity of granulocytes and macrophages as arriving from a blood flow, and local, exerts decisive impact on an outcome of an infection in the local inflammatory center.
Value of phagocytal reaction in And. it was proved by classical researches of I. I. Mechnikov.
Studying of a role of phagocytosis at various steps of an evolutionary ladder — from one-celled and to the highest animals — completely validated this idea, edges received the name of the phagocytal theory of immunity. The numerous pilot studies conducted in many countries of the world did not shake the philosophy of this theory. On the contrary, the theory was buttressed up new by facts, became conventional and strongly entered into gold fund of world science. Cells of two systems take part in reaction of phagocytosis: microphages and macrophages. Granulocytes (basophiles, neutrophils, eosinophils) which the first come to the center of an inflammation concern to microphages. To to macrophages (see) carry monocytes which come from the circulating blood to the infected or damaged fabrics where settle, and also the fixed macrophages in a liver — star-shaped endotheliocytes (Kupfer's cell), spleens, limf, nodes, a thymus gland, adventitious cells of Maximov, histiocytes of connecting fabric. Granulocytes come from cells of marrow. In the course of maturing at them appear double type of a granule: larger, primary, or lysosomes which contain digestive enzymes, acid hydrolases, myeloperoxidase, bactericidal proteins, and smaller by the sizes the secondary granules poorer in enzymes but nevertheless containing an alkaline phosphatase, a lysozyme and lactoferrin — the substances having bactericidal properties. Microphages circulate in a blood channel no more than 6 — 7 hours, in fabrics where they arrive and where the hl is shown. obr. their phagocytal activity, they remain viable within 4 — 5 days. Monocytes circulate in a blood channel up to 3 days, i.e. longer, than granulocytes, and getting into fabrics, they become local macrophages, keeping the viability from one to several months. Monocytes and macrophages under normal conditions do not share, they have primary and secondary lysosomes containing acid hydrolases; in primary lysosomes of monocytes there is also a Peroxidase. In lysosomes of phagocytes it is found more than 25 various proteolytic and hydrolases.
In reaction of phagocytosis distinguish several stages: accession of a phagocyte to a microbe, its absorption, formation of a phagosoma and merge to a lysosome, an intracellular inactivation of the microbe, its enzymatic digestion and removal which remained not destroyed material.
An outer membrane of a phagocytal cell, to a cut the microbe joined, vpyachivatsya, gemmates and forms a phagosoma. The last merges with lizosomalny granules, forming a phagolysosome, and various enzymes and other proteins having bactericidal properties begin to come to it as leads to an inactivation of a microbe, degradation of its macromolecules. After intracellular digestion in macrophages small molecules can be released from a cell, and big molecules and indigestible material remain in secondary lysosomes. Granulocytes as short-lived cells in storage of undigested material of participation do not accept.
Macrophages perform more difficult function, than granulocytes. They can digest bacteria, fungi, protozoa, viruses, complexes antigen — an antibody, and also the changed own erythrocytes, fragments of cells; participate as cells assistants in antibody formation, in protection against cells of malignant tumors. Digestion of the microbes or not microbic antigens absorbed by macrophages is carried out by means of the whole set of lysosomic enzymes. In the course of phagocytosis there is a special enzyme which leads to formation of H2O2, and then and O2. The last is involved in process of an inactivation of fagotsitirovanny bacteria. Hydrogen peroxide takes part in decarboxylation and deamination fat to - t, amino acids, participates in formation of aldehydes which as oxidizers split peptide chains. In the course of phagocytosis there can be various intermediate products promoting an inactivation of microbes. The lysozyme which is contained in phagocytes increases their lytic activity, including and concerning gram-positive bacteria. Not everything, however, microbes are equally pliable to phagocytosis. Existence at bacteria of polisakharidny and polypeptide capsules brakes the first phase of phagocytosis, i.e. their contact with a surface of a phagocyte. Some microbes can breed in phagocytes, without speaking about viruses and rickettsiae which are obligate intracellular parasites. Virulent gonokokk (type 1 and 2) are taken leukocytes and monocytes, but are not digested. Avirulent cultures (type 3 and 4) of gonokokk are exposed to complete phagocytosis. Koagulazopolozhitelny virulent staphylococcus can form micro colonies in a cell and kill her. Some microbes can not only breed in phagocytes, but also remain protected from antibodies or chemotherapeutic means. To kill a tubercular stick in macrophages, it is required in 50 — 100 times more of streptomycin, than for an inactivation of free bacteria. Phagocytal activity is suppressed by exotoxins and endotoxins. Staphylococcal leukocidin destroys leukocytes, and the coagualase slows down phagocytosis. The various enzymes produced by microbes lower activity of phagocytal cells. Virulent parasites can avoid intracellular destruction by destruction of fagosomalny membranes, interfere with merge of phagosomas to lysosomes, suppress metabolism of a phagocyte.
There are, however, also factors capable to activate phagocytal process. One of them — opsonins (see), opened by A. Wright and Douglas (S. Douglas) in 1903 — the substances of normal serum entering a direct connection with microbes thanks to what the last become more available to phagocytosis. The opsonizing action also in particular antibodies, immune, specific to microbes, possess normal.
Discovery of the opsonins and chemotactic factors produced by lymphocytes played a big role in establishment of close connection between cellular and humoral factors of I. Sensibilizirovannye to a certain T-limfotsotsity antigen release active agents (lymphokines) various pharmacological having hemotaksichesky properties for phagocytes. These substances promote attraction of effector cells, in particular mononuklear, in focus of an infection and increase their mikrobotsidny properties. Culture of macrophages, from a cut T-cells were excluded, did not lyse the causative agent of leprosy. Addition to culture of macrophages of lymphocytes from persons with a tuberculoid form of leprosy led to lysis of fagotsitirovanny microbes.
At elicited macrophages metabolic activity increases, they extend quicker and more actively take and digest microbes, the content of hydrolases in them higher. From elicited macrophages plasminogen — the tripsinopodobny enzyme which is taking part in inflammatory reaction is released.
Lymphocytes produce also the substances inhibiting migration of macrophages i.e. there are mediators rendering as stimulating, and overwhelming action on macrophages. Remains still unknown whether the macrophages activated by T-limfotsotsitami differ from the macrophages activated in other ways significantly. The macrophages received from animals, immunizirovanny by bacteria of the sort Salmonella, Brucella had considerably bigger ability to inactivate intracellularly corresponding microbes.
Accession to microbes of opsonins, normal and immune globulins reduces superficial electric potential and that promotes their adsorption on a surface of a phagocyte and to absorption. However the activating action of antibodies on phagocytosis is not limited to it. The antibodies neutralizing exotoxins and endotoxins, and also microbic enzymes promote intracellular digestion of complexes antigen — an antibody. Activity of opsonins increases in the presence of a complement. The leading role in opsonization of bacteria belongs to IgG and SZ.
Virulent bacteria of tuberculosis block merge of phagosomas to lysosomes. If these bacteria before phagocytosis were sensibilizirovana antibodies, then there is a normal formation of phagolysosomes. A leushmania, processed by antibodies, macrophages do not destroy. The antibodies covering toxoplasma allow normal macrophages to carry out merge of phagosomas to lysosomes and to destroy parasites. The similar phenomenon is observed with rickettsiae, a virus of a variolovaccine, as well as other viruses. Connection between phagocytosis of bacteria of a leprosy and a caption of specific antibodies is established. Ability of macrophages to digest M. of leprae depends on the soluble factors which are released activated lymphocytes. At patients with a leprosy decrease in number of the circulating T-cells and increase in number of B-cells is noted. Mice, immunizirovanny the attenuirovanny causative agent of toxoplasmosis, become unreceptive to a virulent strain. As passive transfer of antibodies at this infection does not lead to protection, it is necessary to consider that only the combined action of humoral and cellular factors results in the acquired immunity.
Thrombocytes also take part in reaction of phagocytosis. They influence a chemotaxis, form units with bacteria, spirochetes, trypanosomes and that promote phagocytosis. C-reactive protein also takes part in reaction of phagocytosis. Interacting with surfaces of bacteria, it accelerates phagocytosis, stimulates migration of leukocytes, induces their blasttransformation. S-reactive protein is laid in places of an inflammation on the changed or nekrotizirovanny cells, enters close connection with structures of cellular membranes.
The fixed macrophages limf, nodes, a spleen, a liver, lungs, marrow, an internal wall of vessels and other bodies perform the major barrier function. They purify blood and a lymph of microbes and products of their life activity. In an immune organism barrier function of macrophages considerably increases. It depends both on the opsonizing function of antibodies, and on increase in activity of phagocytes in an immune organism, Macrophages are the major factor providing clearance of blood from viruses, they take and digest virus corpuscles. Macrophages in the presence of the specific antibodies opsonizing and agglomerating viruses and that to promoting process of phagocytosis and disintegration of viruses are especially active. Activity of macrophages depends on genetic properties of an animal and on full value of his food. At the animals raised by food with normal protein content, phagocytal activity of leukocytes was higher, than at the animals who were on a protein-free or reduced-protein diet.
By crossing it is possible to receive posterity of rabbits, high-resistant and highly sensitive to tuberculosis. Macrophages from resistant animals contained more lysosomes, and activity of their hydrolases was higher.
Resistance of macrophages to an infection changes with age. The infected macrophages from young animals can be carriers of a virus, unlike macrophages of adults. In the macrophages received from immune mice, the influenza virus does not breed and antigen of this virus can be found in single cells only within several hours while in not immune macrophages it remains within several days.
All-physiological factors and mechanisms of immunity. All-physiological factors and mechanisms also take great interest in formation of immunity. In addition to temperature increase in the local inflammatory center, for process of recovery also fever has not smaller value. In opinion A. A. Smorodintsev and (1955) and A. Lviv (1962), fever — the main factor promoting process of recovery from a viral infection. The question of the mechanism of action of elevated temperature on viruses and other microbes remains still insufficiently studied. Does it have direct effect on microbes or its influence is mediated, it is required to study still. It is impossible to forget at the same time that at fervescence processes of an immunogenesis amplify, processes of a metabolism accelerate that can also promote an inactivation of viruses, toxins.
Allocation from an organism of viruses, toxins and other decomposition products of microbes with stalemate liquid, a phlegm, excrements, urine and other secrets and excretes can be considered as one of obshchefiziol. mechanisms I. «Secretory», on L. A. Zilber and A. D. Ado's terminology, the mechanism promotes more bystry recovery of relative constancy of internal environment of the organism broken by an infection.
As showed P.F. Zdrodovsky's researches and it sotr., specific and nonspecific factors and mechanisms I. are under the regulating influence of neurohormonal functions of an organism.
High doses of glucocorticoids reduce inflammatory reaction, reduce receipt in the center of phagocytes. Capture of microbes by the last and their digestion under the influence of a hydrocortisone considerably decrease, the hydrocortisone stabilizes membranes of lysosomes and that interferes with receipt from them various hydrolases. Small fiziol, doses of a hydrocortisone promote resistance of an organism to an infection.
Adrenocorticotropic hormone sharply weakens natural immunity of monkeys to a virus of poliomyelitis, and mice — to an influenza virus. Under the influence of a hydrocortisone adult mice become also susceptible to Koksaki's viruses, as well as newborns. Use of glucocorticoids with to lay down. the purpose can conduct to an exacerbation of tuberculosis, increase in number of bacteria in fabrics and a phlegm. Hormonal influence thyroid, a pancreas and gonads on defense reactions of an organism concerning some infections is established.
Factors and mechanisms of artificial immunity
in the course of an infection or after immunization reaction to antigen changes not only at immunocompetent cells (see) and macrophages. As showed I. L. Krichevsky's researches and it sotr., cells of smooth muscles of animals, immunizirovanny brucellous or typroid endotoxin, become unreceptive to these antigens. The condition of areactivity of cells of smooth muscles is specific and St. 2 months remain. The mechanism of this phenomenon is still insufficiently studied. It does not depend on antibodies as other animals do not manage passive transfer of immunity. Apparently, this phenomenon is a consequence of specific immune reorganization of cells.
The question of specific reorganization of the englobing cells in the course of immunization did not receive still definite answer. One researchers explained a superactivity of the phagocytes received from immune animals with the opsonizing action of antibodies, others considered this phenomenon as a result of specific reorganization of phagocytal cells.
Immune macrophages contain more acid hydrolase, the digesting, respiratory and mitotic activity at them is higher in comparison with macrophages from normal animals.
Unlike the nonspecific mechanisms providing inborn immunity antibodies (see) are a factor acquired specific And. They appear as a result of a natural infection or artificial immunization. The specific immune response on bacteria, viruses, toxins and other alien antigens is carried out by immunocompetent cells — T-, B-lymphocytes and macrophages (I eat. Immunocompetent cells, Macrophages). Participation of these three types of cells in a response immune response and their close functional linkage do not raise doubts. However specific mechanisms of relationship between them in the course of formation And. remain still insufficiently studied.
Interaction of antigen with T-limfotsotsitami occurring from thymus (see), leads to their growth and division therefore the number of specifically sensibilized lymphocytes increases. Optimum products of antibodies to the majority of antigens (T-dependent) require cooperative interaction between T - and B-lymphocytes. The antigens consisting of the repeating subunits, napr, the pneumococcal polysaccharide, lipopolisakharida of bacteria polymerized flagellin, polyvinylpirrolidone which can stimulate products of antibodies with plasmocytes in the absence of support function of T-cells — so meet, however. naz. T-independent antigens. The immune response on them is limited to products of antibodies of the class IgM, and formation of cells immunol, memory on these antigens does not occur. However, as showed the researches Braly-Mallena (H. Braley-Mullen, 1974), accession of pneumococcal polysaccharide to erythrocytes of a ram reported to such complex antigen property to cause in mice formation of antibodies of the class IgG, specific to polysaccharide, and formation immunol, memories. Polyvalent antigens can also interact with B-cells directly, forming multiple bonds with the receptors which are on their surface. It is established that function of immunocompetent cells is determined by individual and dominant immune response genes (immunoreactive genes) which are closely connected with genes of histocompatibility. Under the influence of immunoreactive genes cellular and humoral immune responses of an organism on any alien antigens form.
Great success in studying of immunocompetent cells was establishment of the fact that interaction between cells of T, In and macrophages is carried out by the molecules of specific immunoglobulins localized on a surface of cellular membranes. Synthesis of these immunoglobulins is coded by a complex of immunoreactive genes. According to N. Mitchison's hypothesis and soavt. (1974), T-limfotsotsity by means of specific receptors (IgT) distinguish an antigenic structure of the carrier (shlepper), unlike B-lymphocytes which, possessing other receptors, distinguish antigenic determinants of a complete antigen. (Immunizirovanny) T-limfotsotsity activated by antigen produce both specific, and nonspecific substances which, being released from a surface of cells, provide cooperative interaction of macrophages and B-lymphocytes.
The nature of specific factors is still insufficiently studied. Apparently, they consist of a complex of immunoglobulin and antigen or an antigenic determinant. According to Feldman's hypothesis (M. Feldman) and soavt. (1974), this complex (IgT-antigen) after interaction with macrophages who are as if a peculiar condenser of antigenic determinants carries out start of products of antibodies B-lymphocytes. Accession of a complex of immunoglobulin and an antigenic determinant (a specific factor) to superficial structures of macrophages happens thus that antigenic determinants remain free and can interact with receptor structures of membranes of B-lymphocytes. There are also other hypotheses of cooperative interaction of antigen with immunocompetent cells.
The chemical nature and the mechanism of action of a nonspecific factor are also still a little studied. Assume [P. Adams, 1975] that it represents either an immunoglobin fragment, or the small nonprotein molecule possessing hormonal or adjuvant action on B-lymphocytes.
The last come from small marrowy lymphocytes on which surface of membranes in the course of maturing in a spleen and limf, nodes immunoglobin (Ig) receptors — predecessors of antibodies form. Under the influence of antigenic determinants B-lymphocytes proliferate, grow and turn into the plasmocytes capable to active synthesis and secretion of antibodies.
According to the clonal and selection theory of Burnett (1971), the special immunoglobin receptor capable to interact with a certain antigenic determinant is inherent in each clone of B-lymphocytes. Along with the short-lived plasmocytes producing antibodies there are long-living B-lymphocytes bearing function immunol of memory, thanking the Crimea anamnestic reaction is carried out. Interaction of cells of T, In and macrophages happens in follicles of the centers of reproduction and in a red pulp of a spleen. Described by the Item. The areactivity of an organism to alien antigen which is caused administration of this antigen in the embryonal period concerning viruses and bacteria is not finalized by the medical Avar (1953) and M. Gashek (1953). It was noted that at the congenital viral infections caused, e.g., by Gross's viruses or a lymphocytic choriomeningitis in mice, free antibodies to these viruses are not found or are in it is insignificant trace amounts, as gave the grounds to treat this phenomenon as a state true immunol, tolerances. However more careful studying showed, as at these congenital infections of an antibody are formed, but there are they hl. obr. in the state connected with a virus are also found in the form of a complex antigen — an antibody on membranes of cells of kidneys and vessels.
Immune responses, both cellular, and humoral, can be artificially suppressed by repeated introduction of high doses of antigen therefore there comes on a nek-swarm time an immunological paralysis (see. unresponsiveness ).
Products of antibodies submit to the general patterns of biosynthesis of proteins and occur on ribosomes of plasmocytes. Coding of synthesis of specific immunoglobulins is carried out by the DNA system — RNA of a cell, antigen, apparently, carries out starting function, but does not play the creating role in formation of a molecule of immunoglobulin. There is a hypothesis, according to a cut antigen causes derepression of the genetic information coded in cells of the corresponding clone.
Specificity of antibodies — one of their major properties. Antibodies in relation to one species of a microbe do not interact with other species of microbes if the last have no general for them antigenic determinants. Availability of the general antigens is the reason of cross-reactions. Presence at antigen of several antigenic determinants can stimulate formation of several types of antibodies.
The molecules of antibodies more weakly reacting with antigen have smaller compliance to an antigenic structure of a determinant, and more avidny molecules reproduce essential features of spatial configuration more precisely hapten (see).
Specific immunoglobulins are one of the major factors acquired humoral And. They neutralize microbes and products of their life activity — toxins, enzymes, as well as other alien antigenic substances of an animal and plant origin. Value of immunoglobulins among which distinguish 5 classes (IgM, IgG, IgA, IgD, IgE), in acquired And. unequally. The greatest role is played by IgG, IgA and IgM while the protective IgD and IgE function is rather small. Moreover, connect developing of an allergy with IgE. IgG make apprx. 70 — 80% of normal human immunoglobulins, and IgD and IgE are in serum in rather low concentration (see. Immunoglobulins ).
Part of a molecule of an antibody where the active center is localized, carries the name of a Fab-fragment. Ability of an active center of a molecule of immunoglobulin to react only with a certain antigenic determinant depends on its specific three-dimensional structure formed by a small number of amino acids. The mutual sterichesky complementarity of an active center of an antibody and determinant group of antigen is the cornerstone of specific interaction. Antigen and an antibody quite strongly keep together van-der-vaalsovymi and hydrogen forces of an intermolecular attraction. However compound of antigen with an antibody is not irreversible. The toxin neutralized by antibodies can be in whole or in part recovered. Performs important function as well other part of a molecule of immunoglobulin called by a Fc-fragment. The last gains ability to fix a complement (C1) after accession to a molecule of an antibody of antigen. It must be kept in mind also a possibility of communication of a Fc-part of the molecule IgG, independent of antigen, with components of a cell wall of stafilokokk (a protein And) and streptococci [Stephens, Read (S. of Stephens, W. Reed, 1974) with sotr.], and also accession of reagins (IgE) Fc-fragments of their molecules to receptors of basophiles and mast cells that is an initial phase in development of an allergy.
Immunoglobulins lower a degree of dispersion of soluble antigens, cause their precipitation, flocculation, and in corpuscular antigens (viruses, bacteria, spirochetes, the elementary) — agglutination and agglomeration. The complexes of immunoglobulin and a complement fixed on membranes of spirochetes, trypanosomes and vibrioes adsorb thrombocytes. The microbes loaded thus become less mobile, are agglomerated, disappear from blood quicker, actively being late in an adenoid tissue of a spleen, limf, nodes and other bodies. The toxin neutralized by antibodies loses ability to join receptors of sensory cells. The enlarged complex (toxin, antitoxin, a complement) is late in barrier bodies (limf, nodes, a spleen, a liver, etc.) and becomes an object of phagocytes. Action of antibodies and on viruses is similar. Specific antibodies, connecting to viruses, block their receptors, change physical. - chemical properties of superficial structures of virion thanks to what the virus loses ability to be adsorbed on a sensory cell and to get into it. Protective function of antibodies in an organism comes down to neutralization of viruses on their way to a sensory cell, dissociation of contacts between them (see. virus-induced immunity ).
Very trace amount of antibodies can protect from developing of a viral infection. Only two or four molecules of an antibody, having joined critical places of a shoot of a phage, are capable to prevent joining of the last to bacteria. With the participation of a complement of IgM and IgG bacteria, spirochetes, trypanosomes can lyse. The question of a possibility of an immune lysis of viruses remained open for a long time. M. A. Morozov and M. P. Korolkova (1939) reported that antibodies can cause a lysis of a virus of smallpox with total loss of its infectious properties. In 30 years there was Almeyda and Uoterson's message (J. Almeida, A. Waterson, 1969) about an immune lysis of viruses of infectious bronchitis of birds and rubellas. At a virus of infectious bronchitis of birds, sensibilized antibodies and a complement, under a supermicroscope observed increase in an outside rim of virion and emergence of «dents» in an outside cover.
Enzymatic action of a complement can take place only when Ig joins the cover containing a lipoproteid.
As showed Oroslan and Gilgin's researches (S. Oroszlan, R. Gilgin, 1970), processing of a virus of a leukosis of mice immune serum and a complement led to release from a virus of group-specific (gs) antigens, and the virus at the same time became sensitive in RNK-aze that demonstrated destruction of virions. The immune serum and a complement taken separately did not cause such changes.
Characteristic changes at a virus of tumors of hens as a result of processing by its immune serum and a complement observed Opua and Vizhye (M. of Aupoix, P. Vigier, 1975) under a supermicroscope. Morfol, changes preceded a virolizis.
The complement exponentiates activity of antibodies, accelerates an inactivation of a virus [H. Heineman, 1967]. Activity of early antibodies at primary herpes infection depends on a complement. Accession of a complement to a Fc-part of the antibody connected with antigen creates additional sterichesky hindrances for virus receptors and subjects increases action of antibodies with a low caption which in itself could close tsitotropny receptors of a virus only partially. Virus neutralizing activity of serums of adults (at repeated herpes) amplifies by 2 — 4 times at addition of a complement.
Clarification (clearance) of blood from toxins, viruses and other microbes under the influence of antibodies considerably accelerates. As showed Shultts's researches (I. Schultz, 1966), at normal rats in an hour after intravenous administration 10^7,5 TTsPD50 of a virus of poliomyelitis small decrease in a titre of a virus was noted. At immunizirovanny rats in 10 min. falling of a titre of a virus more than on 5 lg was observed. The index of clarification of blood in an hour after an injection of a virus at normal rats made 1,66, and at immunizirovanny — more than 5.
The opsonizing and agglutinating action of antibodies on viruses has, apparently, fundamental value for elimination of a virusemia.
The opsonizing effect of immunoglobulins concerning one and all antigens, both soluble, and corpuscular is established. Antibodies promote process of phagocytosis and disintegration of alien antigens. Neutralized by antibodies, they are exposed to digestion easier. Antibodies have more or less pernicious effect not only on bacteria, toxins and viruses, but also on spirochetes, trypanosomes, plasmodiums of malaria, leushmania, toxoplasma. In places, endemic for malaria, napr, in Gambia, children are born rather steady against malaria within the first months of life, apparently, thanks to transfer it from mother of the antibodies neutralizing plasmodiums of malaria. Later, aged from 1 year and up to 5 — 8 years, children are susceptible to a disease. Under the influence of immunoglobulins there are new antigenic options of the spirochetes, trypanosomes steady against the first generation of antibodies that also demonstrates direct effect of immunoglobulins on these microbes. Apparently, antibodies possess a leading role in emergence of new antigenic options of influenza viruses. When microorganisms (gonokokk, brucellas, bacteria of tuberculosis, a leprosy and, especially, viruses) are localized intracellularly, antibodies are ineffective.
In functions of immunoglobulins of various classes there are features. IgM (19S) appear as a result of priming reaction of an organism on administration of antigen — early antibodies. They manage to be found already in 24 — 36 hours after intravenous administration to mice of an influenza virus.
Definition of antibodies of the class IgM can be used for early diagnosis of an infection and establishment whether initially it arose. Antibodies of this class take part in neutralization of pathogenic microbes already in the earliest stage of an infection. They are more active concerning large corpuscular antigens. The macroglobulins received from a rabbit by 750 times are more active in an agglutination test of erythrocytes of the person of group A in comparison with antibodies of the class IgG. 198 antibodies and concerning cholera vibrioes and Fleksner's shigellas were more active. Antibodies 19S by 100 — 1000 times are more active in reaction of hemolysis at recalculation on one molecule, than antibodies of a class 7S. Immunoglobulins of the class IgM more actively, than all other classes of immunoglobulins, attach a complement. The complement is activated even by one molecule IgM while obtaining similar result requires not less than 20 molecules IgG. Antibodies of the class IgG to which lot the major protective function falls are formed later, than antibodies of the class IgM — on the 2nd week after the beginning of immunization. Apprx. 70 — 80% of immunoglobulins of active specific serums belongs to the class IgG. Antibodies of this class are studied better, than antibodies of other classes.
Antibodies of the class IgG are especially effective in neutralization of finely divided antigens: toxins, viruses. At a repeated infection or immunization of an antibody of IgG memories to the corresponding antigens are developed early thanks to existence of cells immunol, that can serve as an indicator of secondary infection. The molecules IgG owing to the small sizes can get through a placenta from mother to a fruit and cause transplacental And., remaining within several months after the birth. Aviditet of antibodies, i.e. speed of their reaction with antigen and durability of formation of connection with it, raises in the course of immunization. Early anti-toxic serums possess lower aviditet, than late. The same serum may contain several populations of antibodies of various avidnost. Only the serums taken very much early or, on the contrary, very late, contain, as a rule, antibodies of an identical avidnost (see. Aviditet ).
Formation of immunoglobulins of this or that class depends not only on duration; immunizations, but also from properties of antigen, its dose, way of introduction, and also from a look and age of animals.
For neutralization of antigens and bigger durability of binding of their determinants the valency of antibodies matters. Bivalent antibodies are more active and aviditt them above, they can neutralize viruses or bacteria at more low concentration, than monovalent. Bivalent antibodies as showed the Form, Lesley (S. Blank, G. Leslie) and soavt. (1972), neutralize viruses by 1000 — 2000 times, it is better, than monovalent. However there is no direct ratio between increase in valency of antibodies and strengthening of their neutralized activity. The dissociation rate at a complex monovalent antibodies — antigen is higher, than at a complex of the same antigen with bivalent antibodies. At bivalent molecules of antibodies energy of connection with antigen is higher, than and explain their smaller dissociation rate. Assume [Klinman, Long (N. Klinman, S. Long) and soavt., 1967] that bivalent antibodies arose in the course of evolution later as further improvement of function of immunoglobulins that promoted increase in protection of an organism against infectious agents.
Antibodies of the class IgA drew especially great attention to themselves after their value in formation of local immunity was shown. The idea of existence of the most vulnerable places for an infection in an organism was stated still to A. M. Bezredkaya in 1919. So, skin, in his opinion, represents locus minoris resistentiae for the activator of a malignant anthrax, and an intestinal path — for enterobakteriya; increase in resistance of fabrics, the most sensitive to microbes, would be followed also by the general And. In spite of the fact that continuous communication between local and the general And. became obvious, the hypothesis approving value of local specific and nonspecific factors for emergence and development of an infection received experimental and a wedge, confirmation.
The antibodies which are present at secrets of respiratory tract play an important role in protection against respiratory viruses. To development of a problem local And. opening of a new class of immunoglobulins — IgA — and among them antibodies of secretory type promoted. These antibodies received such name because contain in secrets of respiratory and went. - kish. paths, colostrum and other liquids in much bigger concentration, than in plasma. In washouts from a mucous membrane of a trachea and bronchial tubes of IgA make up to 53% of total quantity of the protein found in them while IgG — no more than 15%. The most high level of secretory IgA is defined in women's milk. The class IgA is heterogeneous and includes the options of antibodies unequal on structure and molecular properties. So, e.g., IgA has a pier. weight is 160 Ltd companies and a sedimentation constant 7S. It contains hl. obr. in serum, and in secrets — in insignificant quantity. In secrets also the immunoglobulin, unique on the structure and properties, which is also carried to the class IgA, making actually secretory antibodies is found. They meet in the form of dimer and trimmers, i.e. have respectively four and six valencies. Pier. the weight of dimer apprx. 400 000, and is higher than trimmers. A sedimentation constant of these antibodies — 11S — 14S — 18S. In a molecule of secretory IgA, both the dimeasure, and the trimmer, enters an intracellular transport piece — a glycoprotein about a pier. it is powerful apprx. 60 000, containing! apprx. 9,5% of carbohydrates, sialine to - that. Consider that the intracellular transport piece, joining in the molecule IgA, stabilizes it, increases permeability through intercellular spaces and reports proteolytic enzymes resistance that is important as antibodies of this type can be and function in the environment rich with enzymes.
As the proof of local formation of IgA(11S), but not its transudation from plasma serves that the caption of these antibodies in secrets after intranasal immunization can be higher, than in serum.
Molecules of secretory IgA are synthesized by the plasmocytes localized in subepithelial fabrics, and their connection with an intracellular transport piece which is produced by epithelial cells of mucous membranes went. - kish., respiratory tract, etc., occurs upon transition through the surfaces of mucous membranes. In addition to IgA, find IgG and IgM which can arrive also by perfusion from blood in a secret of a nose.
Secretory antibodies are of great importance in protection against the microbes getting into an organism through the surfaces of mucous membranes. Role local And. and secretory antibodies it is especially important at those infections for which the surfaces of mucous membranes are at the same time entrance gate and the place of localization of the activator. And. to certain infections, napr, to flu, correlates with secretory antibodies better, than with serumal. Secretory antibodies, as well as antibodies serumal, have ability to neutralize viruses, toxins, bacteria. Stay them on the surface of mucous membranes, i.e. at the place of entrance gate for many microbes, has often crucial importance for the prevention of emergence and development of an infection.
Local (aerosol) introduction of a vaccine is better, than parenteral, protects from infection with an influenza virus and a disease. Introduction of a vaccine directly in respiratory tracts provides higher caption of secretory antibodies and big duration of products them, than at hypodermic vaccination. Parenteral vaccination is more effective for formation of serumal antibodies.
Butler, Valdmann (W. Butler, T. Waldinann) and soavt. (1970) report that secretory antibodies appear already in 24 — 48 hours after infection with a virus of Koksaki or a rhinovirus, transudation from a blood plasma of albumine and IgG was observed later — during a disease that also confirmed local formation of IgА(11S) - antibodies. They explain early emergence in secrets of IgA with release from cells of preformirovanny antibodies, assuming that examinees were infected with Koksaki's virus of the 21st type and a rhinovirus of the 15th type earlier. However, as showed pilot studies, specific antibodies to an influenza virus begin to be produced by de novo in 24 — 48 hour. Therefore it is impossible to explain early emergence of antibodies in secrets, and it is equal also in serum at initially immunizirovanny animals release them from preformirovanny cells. It is necessary to acknowledge the possibility of their earlier education rather, as it was shown concerning antibodies to various antigens. Intramuscular and hypodermic introduction of an influenza vaccine is insufficiently effective for induction of antibodies in secrets of a nose even if the antiserum capacity in serum was rather high.
There is no correlation between the maintenance of antibodies in serum and in secrets of a nose. These can explain the cases of flu observed sometimes in the presence of antibodies in serum.
Secretory antibodies have not smaller value also at intestinal infections of a virus and bacterial origin. The hypothesis of the koproantitela resulting from a local antigen challenge received confirmation.: In excrements of patients with dysentery agglutinins on 1 week of an infection when in serum they still were absent are found. At animals and people after oral immunization found antibodies to cholera vibrioes in excrements. Virus neutralizing antibodies are found in excrements of patients with poliomyelitis and vaccinated. The relation of concentration of virus neutralizing IgA to IgM in a secret of a duodenum was higher, than in serum that testified to local products of secretory antibodies to a virus of poliomyelitis. Keller, Duayer (R. Keller, J. Dwyer, 1968) found in excrements of patients with poliomyelitis of an antibody of IgA, the neutralizing poliomyelitis viruses while in serum they were absent. Except IgA, in excrements there are IgG and IgM which can be as a local origin, and to arrive from a blood plasma.
Antibodies of IgA in a low caption can appear in intestines already in 1 week after peroral introduction of a vaccine. Parenteral immunization by the inactivated vaccine stimulates formation of humoral antibodys and subjects prevents emergence of paralytic forms of poliomyelitis, however resistance of a small intestine to an infection is shown at the same time in weak degree. Peroral immunization by an attenuirovanny poliomyelitis virus results in resistance of a small intestine. The antibodies circulating in serum can prevent a viremiya, but they are not able to prevent infection of cells of a mucous membrane of respiratory tracts and intestines. Only the antibodies washing the surfaces of mucous membranes can prevent infection with viruses and bacteria. Secretory IgA play a large role in regulation of bacterial and virus flora in cells of mucous membranes, in protection them from an infection.
Existence of antibodies in intestinal contents can complicate allocation of a poliomyelitis virus from excrements, and only processing of the examinee of material to - that (at pH 2,2) leads to dissociation of a complex antigen — an antibody and to increase in percent of detection of a virus. This fact demonstrates action koproantitet in vivo.
As showed researches of Nyyukomba, Isidzak (R. Newcombe, To. Ishizaka) and soavt. (1969), products of antibodies after topical and parenteral administration of a diphtherial anatoxin are not identical. Higher caption of anti-diphtheritic antibodies of the class IgA (11S) in secrets (at intranasal administration of anatoxin), than in serum, testified to their local origin, but not to transudation from a blood plasma. Along with antibodies of the class IgA(11S) diphtheritic antitoxins of the class IgG which can locally be produced and arrive from blood also were found in secrets of a nose of some persons.
Question of value of antibodies of the class IgD and IgE for And. it is still insufficiently studied though there are bases to assume, as these immunoglobulins perform protective function. However features of structure and function of these antibodies and their small concentration in comparison with IgG, IgA and IgM allow to assign them a smaller part in protection of an organism against an infection.
Almonds, adenoides, bronchial and mezenterialny limf, nodes contain the cells producing IgE. In a spleen and in hypodermic limf, nodes these cells are presented poorly. Antibodies of the class IgD are found in contents went. - kish. a path where arrive, apparently, as a result of their secretion from local plasmocytes. Secretory and serumal IgD and IgE are identical, they have no intracellular transport piece.
the Possibility of acquisition was known to the theory of immunity for an organism of immunity to the infectious disease postponed once long ago. However the reasons of it long remained unknown. Were already carried out a smallpox inoculation, a malignant anthrax, rage by the vaccines offered by E. Jenner and L. Pasteur, however any of the factors and mechanisms which are the cornerstone acquired as a result of inoculations And., it was not established.
Opening of microbes — the specific reason of diseases was of great importance for the solution of this problem. Not accidentally therefore that the first progress in development of immunology directly followed success achieved by microbiology. Opening of causative agents of diseases, their toxins gave the chance to approach closely studying of the factors and mechanisms counteracting them.
Theory of «exhaustion of the environment», offered by L. Pasteur in 1880, was one of the first attempts to explain an origin of the acquired I. Nevospriimchivost, being caused the disease postponed once, was explained by the fact that microbes completely used the substances, necessary for their life, which were to a disease in an organism and therefore did not breed in it again just as they cease to breed on an artificial medium after long cultivation in it.
Treats the same time and retentsionny theory of immunity, offered Shovo (I. Century of A. Chauveau), according to a cut the growth inhibition of bacteria was explained by accumulation in an organism of the special products of exchange interfering further reproduction of microbes. Though the retentsionny theory of P. as well as a hypothesis of «exhaustion of the environment», were speculative, nevertheless they to some extent reflected objective reality. Shovo's hypothesis contained already hints on a possibility of emergence as a result of an infection or immunization of some new substances braking activity of microbes in case of secondary infection. Those as it was shown later, antibodies are.
Phagocytal theory of immunity, the cut was a founder I. I. Mechnikov, was the first experimentally reasonable theory of immunity. It was highly appreciated by L. Pasteur as the recent and original trend. Stated for the first time in 1883 in Odessa it successfully was developed further in Paris by I. I. Mechnikov and his numerous employees and pupils. The phagocytal theory, an essence a cut is stated above, repeatedly was a subject of heated scientific debates, and her author for many years had to uphold correctness of the idea in scientific disputes with many world famous scientists — P. Baumgarten, R. Koch, R. Pfeyffer, K. Flyugge, etc. Time and the facts, however, completely confirmed paramount value of phagocytal reaction in protection of an organism against an infection, and the phagocytal theory And. gained the general recognition. Further specifications and additions were made to it. It was established that capture and digestion by phagocytes of disease-producing agents not the only factor of protection of an organism. There are microbes, napr, viruses for which phagocytosis in itself is not of so great importance as at bacterial infections, and only preliminary impact on viruses of antibodies can promote their capture and destruction.
It was impossible, proceeding only from the phagocytal theory, to explain the mechanism of the acquired resistance to toxins. Opening to E. R and A. Yersin in 1888 of diphtheritic toxin, and E. Beringom and S. Kitasato in 1890 of antitetanic, and then and antidiphtherial antitoxins was the fact which forced to go beyond the phagocytal theory and to reckon with protective action of humoral mechanisms. In I. I. Mechnikov's laboratory his pupils and sotr. — Zh. Borde, F. Ya. Chistovich, etc. — conducted basic researches of factors humoral And. — the nature and properties of lytic agents is studied, pretsipitina to proteins of animal origin are open.
Without denying value of antibodies, I. I. Mechnikov suggested that they are produced by phagocytes. In formation of immunoglobulins plasmocytes macrophages, and the lymphoid cells close by origin to Mechnikov's microphages are directly involved, carry out both function of recognition of antigens (T-cell), and synthesis of immunoglobulins (V-cell). Phagocytal reactions are mighty, however not the comprehensive mechanism of protection of an organism against microbes. E.g., in protection of an organism against toxins and other soluble alien antigenic substances of an animal and plant origin, and also against viruses the main role belongs to humoral factors — antitoxins and other antibodies. Paying tribute to antibodies, it should be noted, however, that connection, e.g., with toxin does not lead them to its destruction, and it can be recovered in simulated conditions again. The complexes neutralized by antibodies are taken phagocytal cells and are digested. Cellular reaction on the alien antigenic agent is not only phagocytal reaction, but also the reaction of immunocompetent cells conducting to antibody formation. So closely cellular and humoral factors of protection of an organism intertwine in the uniform mechanism.
I. I. Mechnikov emphasized one party of cellular defense reaction — phagocytal. The subsequent development of science, however, showed that functions of phagocytal cells are more various: except phagocytosis, they participate in products of the antibodies, interferon, a lysozyme and other substances which are of great importance in formation And. Moreover, it is established that not only cells of an adenoid tissue, but also others take part in immune responses. E.g., all cells are capable to produce interferon, the glycoprotein fragment of secretory antibodies is produced by epithelial cells of mucous membranes, many cells, and not just cells of reticuloendothelial system produce virus inhibitors. These facts, as well as many others give the grounds to speak about cellular immunity in broad understanding, including also phagocytal reaction as the major and evolutionarily the most ancient form of protection. Along with the phagocytal theory And. the humoral direction developed, a cut assigned a leading role in protection against an infection to liquids and juice of an organism (blood, a lymph, secrets) which contain the substances neutralizing microbes and products of their life activity.
Humoral theory of immunity many outstanding researchers therefore it is unfair to connect it only with a name of P. Ehrlich though and belong to it, undoubtedly, many fundamental opening connected with antibodies created.
Y. Fodor (1887), and then J. Nattoll (1888) reported about bactericidal properties of blood serum. G. Bukhner (1889) established that this property depends on existence in serum of the special thermolabile «shielding agents» called by it alexins. Zh. Borde (1898) working in I. I. Mechnikov's laboratory presented the facts testimonial of participation in tsitotsidny effect of two substrates of serum, various on the properties — a thermolabile complement and a thermostable antibody. Great value for formation of the theory humoral And. had opening E. Beringom and
S. Kitasato (1890) abilities of immune serums to neutralize tetanic and diphtheritic toxins, and P. Ehrlich (1891) — the antibodies neutralizing toxins vegetable (ricin, abrine) of an origin. In immune serums, Guinea pigs, received from resistant to a cholera vibrio, R. Pfeyffer (1894) found the antibodies dissolving microbes; administration of these serums not immune animal told them resistance to a cholera vibrio (see. Isaeva-Pfeyffera phenomenon ). Opening of the antibodies agglutinating microbes [Gruber, Durham (M. of Gruber, H. Durham), 1896], and also antibodies, precipitant products of their life activity [R. Kraus, 1897], confirmed direct action of humoral factors on microbes and products of their life activity. Receiving to E. R (1894) serums for treatment of a toxic form of diphtheria finally strengthened the idea about a role of humoral factors in protection of an organism against an infection.
To supporters cellular and humoral And. it seemed that these directions are in a sharp, irreconcilable contradiction. However further development of science showed that between cellular and humoral factors And. there is close interaction. E.g., such humoral substances as opsonins, agglutinins and other antibodies promote phagocytosis: joining pathogenic microbes, they make them more available for capture and digestion by phagocytal cells. In turn phagocytal cells take part in the cooperative cellular interactions conducting to products of antibodies.
From modern positions it is visible, as cellular, and humoral theories And. correctly reflected its separate parties, i.e. were unilateral, but did not cover the phenomenon in general. Recognition of value of both theories was simultaneous award in 1908 to I. I. Mechnikov and P. Ehrlich of the Nobel Prize for outstanding merits in development of immunology. P. Ehrlich (1897) one of the first tried to get into the mechanism of education by cells of antibodies. The last as he considered, are formed by the same cells, with to-rymi also antigen, napr interacts, toksinony This position of P. Ehrlich did not find, however, confirmation. The tetanin has tropism to cells of nervous tissue, and antitoxin, as well as all other antibodies, is developed only by plasmocytes irrespective of what cellular systems antigen perniciously affects.
One of the most important merits of P. Ehrlich is creation receptor theory. In a basis of interaction of toxins with antitoxins and cells, sensitive to toxins, as well as any antigens with cells and antibodies, the chemical principle — existence special specific to each antigen and an antibody of structures — receptors by means of which interaction between cells, antigens and antibodies is carried out was put. Concepts about the receptors fixing substances — chemoceptors, and also the receptors fixing antigens were entered. The receptors which separated from cells are, according to P. Ehrlich, antibodies. Having created the receptor theory, P. Ehrlich in many respects anticipated modern theories of antibody formation, their interaction with antigens. Existence of specific immunoglobin receptors at the T-cells distinguishing antigens, receptors at B-cells and macrophages, active centers at molecules of antibodies and determinant groups, complementary to them, at antigens is one of the most important achievements of modern immunology. The cellular and humoral directions proved by I. I. Mechnikov and P. Ehrlich's works in studying And. continue to develop successfully.
Since I. I. Mechnikov and P. Ehrlich many theories were offered And., though in strict sense of the word they could not apply for the name of special theories as concerned only separate, though important, but private questions: the mechanism of antibody formation, their specificity, the mechanism of compound of antigen with an antibody, etc., did not explain a phenomenon And. in general, i.e. mechanisms of the hereditary and acquired immunity of an organism to various infectious diseases. Many of these theories are of only historical interest.
The significant contribution to development of the general immunology was made by experimental and theoretical researches F. Burnett (1972) — the author of the klonalno-selection theory of antibody formation (see. Antibodies ). This theory promoted studying of immunocompetent cells, a role them in specific recognition of antigens, products of antibodies, emergence immunol. tolerances, autoimmune processes, allergy.
Despite a certain progress in studying of specific and nonspecific factors and mechanisms I., many parties it far are not revealed yet. It is unknown why concerning one infections (measles, smallpox, parotitis, poliomyelitis, a tularemia, etc.) the organism is capable to create intense and long And., and concerning other infections acquired by an organism And. it is short, and the same type of a microbe in the antigenic relation can cause recurrent diseases through rather short time terms. Also the reasons of small efficiency of immune factors concerning a bacteriocarrier, and also activators hron are not known, and latent infections, napr, a virus of a herpes simplex which for a long time, and sometimes and for life can persistirovat in an organism and cause to pass periodic exacerbations of an infection while other diseases come to an end with sterile I. Objyasnit it only with ability of a virus of herpes directly from the struck cell into normal, passing the extracellular environment, it is hardly possible as the same mechanism of transition from a cell to a cell is observed also at the virus of smallpox causing resistant sterile And. It is not established why in one cases factors and mechanisms I. are capable to liquidate infectious process and to exempt an organism from pathogenic agents, and in other cases the condition of a peculiar balance between a microbe and an organism which is periodically broken in that, in other party for many years is established (tuberculosis, a leprosy, etc.).
Apparently, the mechanism of immunity and release of an organism from microbes, uniform, universal for all infections, does not exist. Features of a pathogeny of various infections find the reflection and in features of the mechanisms providing And., however there are general principles characterizing a way of protection against microbes and other alien antigenic substances. It gives the grounds for creation, the general theory of immunity. Allocation of two aspects And. — cellular and humoral — it is justified by methodical and pedagogical reasons. However any of these approaches does not give the sufficient grounds for creation of the theory And., edges comprehensively would capture the essence of the observed phenomena. Both the cellular, and humoral factors which are artificially isolated characterize only the separate parties of the phenomenon, but not all process in general. In creation of the modern theory And. shall find also the place and obshchefiziol. factors and mechanisms: temperature increase, secretory and secretory and enzymatic functions, neurohormonal influences, activity of a metabolism etc. Molecular, cellular and obshchefiziol. the reactions providing protection of an organism against microbes and other alien antigenic substances shall be presented as the uniform, interconnected, evolutionarily developed and genetically determined system. From here it is natural that genetic determination of an immune response on alien antigen, just as again acquired factors and mechanisms, shall be considered at creation of the modern theory And.
Immune responses perform not only special function of protection against microbes and products of their life activity, but carry also another, more various fiziol, function. Immune responses take part and in release of an organism from various is mute also the trial antigenic substances getting through a respiratory and digestive tract, through the injured skin (poisons of arthropods, snakes), and also which are artificially entered with the medical purposes (serums, blood, drugs, allogenic transplants). Answers all these substrates genetically different from antigens of the recipient, an organism with a complex specific and nonspecific cellular, humoral and obshchefiziol. the reactions promoting their destruction, rejection and removal. Value of immune responses and in prevention of emergence at experimental animal malignant tumors of a virus etiology is proved (see. atrepsy ).
The hypothesis is stated (F. Vernet, 1962; R. V. Petrov, 1976) that the immune system of an organism carries out function of supervision of genetic constancy of set of somatic cells. Specific and nonspecific defense reactions play an important role in preservation of life on the earth. However perfection of immune responses, as well as all others, relatively, and under certain conditions they can do also harm. E.g., the organism answers repeated receipt of high doses of a foreign protein with rough and rapid reaction, edges can end with death (see. Acute anaphylaxis ). By relative imperfection it can be characterized and such powerful defense reaction as an inflammation, a cut in case of localization in a vital leads it sometimes to big and irreparable destructions of fabrics.
Function of separate protective factors can be not only is weakened, but also changed. If normal immune responses are directed to extermination of alien agents — bacteria, toxins, viruses, etc., then in pathology these reactions begin to work also against own normal, not changed cells and fabrics.
Thus, immune responses, protective by the nature, can be under certain conditions the cause and patol, states: allergies, autoimmune processes, etc. (see. Autoallergichesky diseases , Autoallergy , Autoantibodies , Immunopathology ).
Immunity at parasitic diseases
started studying of immunology of parasitic diseases rather recently: in 1929 there was the first book on And. at parasitic diseases of W. Taliaferro. Further the attention to this problem considerably amplified.
And. at parasitic diseases submits to the same patterns, as And. at bacterial infections, though has the features.
Hereditary And. can be absolute, causing full immunity of the owner to a parasite. E.g., macaques Rhesus factors are unreceptive to the activator of a tetrian fever Plasmodium vivax; many animal species are unreceptive to eurysynusic helminths of the person — a bull and pork tapeworm, and the person does not catch a number of helminths and causative agents of malaria of animals. Quite often hereditary And. has relative character as many parasites unusual for this type of the owner can make nevertheless in his organism a part of the life cycle. So, parasitizing causes development of a heavy symptom complex of «larva migrans» in the person of larvae of a number of helminths of animals. Tension hereditary And. amplifies with age owing to what young animals are more susceptible to protozoan to infections and helminthoses, than adults, and the disease proceeds at them heavier. Mechanisms hereditary And. are studied poorly, however its dependence on genetic factors is known. It is established that the indigenous people of the Western Africa is unreceptive to Plasmodium vivax, and at the persons who inherited abnormal type of hemoglobin (HbS) easier course of tropical malaria is observed. Apparently, genetically caused deficit glyukozo-6-fosfatdegid-rogenazy has the similar, only less expressed effect. Hereditary And. it can be weakened by a splenectomy, radiation, action of immunodepressants. It is known, e.g., that the person is absolutely steady against a piroplasmosis, however after a splenectomy infection leads to a lethal outcome.
Acquired And. can have various manifestations. Acquired And. to helminths it is characterized by a number of the features caused by complexity of their structure and the large sizes, stability of the number connected with lack of reproduction in a body of the owner, staging of life cycles in the course of which interaction of the owner and a parasite changes. Acquired And. to helminths carries relative, but not absolute character more often, its tension at different stages of development of an invasion is various and quite often depends on intensity and frequency rate of infection, and validity period can be limited to the period of stay of parasites in an organism of the owner. The most brightly acquired And. it is expressed concerning fabric (trichinellas, an echinococcus, shistosoma, filarias) and intestinal migrating (ascarids, ankilostomida) helminths. The main immunizing impact is made by the larvae which are the most active producers of antigens, especially in the period of molts. Antigenic activity tissues of a body, secrets and excretes of helminths have.
Manifestations And. are various, the main of them: decrease in extensiveness and intensity of repeated invasions, delay of development of helminths and reduction of terms of their life, oppression of reproductive activity. And. it is transmitted from mother to posterity with milk and through a placenta.
Mechanisms I. include action of the antibodies relating generally to IgG, IgM, reagins and cellular reactions. Antibodies can damage a tegument of helminths, create the precipitated calcium superphosphates around their output openings breaking normal biochemical processes, to connect enzymes. Substantial increase of the IgE level is characteristic of helminthoses, reagins belong to Krom. The last create, apparently, barriers in skin and mucous membranes of intestines, respiratory tracts and so forth, the interfering migrations of larvae. Participation in mechanisms I is established. allergic reactions of the immediate and slowed-down types connected with development of inflammatory processes, formation of granulomas around parasites and so forth.
At the population of zones, endemic on an ascaridosis, ankilostomidoza, filariases, a schistosomiasis, etc., as a result of development And. stabilization of level of a prevalence and intensity of an invasion, its termination on an early phase, and also subclinical disease and an asymptomatic parasitosis is observed. In this regard the great value for understanding of the course epid, process has immunol, inspection of the population for the purpose of studying of size of an immune layer, identification of the contingents which are in conditions of high risk of infection, specification of intensity of transfer of an invasion and assessment of efficiency of the held events.
Acquired And. at protozoan infections can be sterile, remaining a long time after disappearance of parasites (visceral and some forms of a skin leushmaniosis) and unsterile (premunition), the limited period of stay of parasites in an organism of the owner (malaria, a coccidiosis, etc.). In formation of PI. both humoral, and cellular factors which role at different infections is not identical participate.
At malaria the antibodies revealed in blood in several days after emergence of erythrocyte forms of plasmodiums have the dominating value. In certain cases they manage to be revealed even through a long time after elimination of parasites, especially in cases of repeated infections. During a fabric phase of an infection of an antibody do not come to light. At reinfection increase in antiserum capacities in hundreds of times in comparison with primary infection is observed. Antibodies at malaria belong to IgM and IgG. The antibodies of both classes operating on extracellular forms of parasites — merozoites and interfering, obviously, to their penetration into erythrocytes have protective value, apparently. At indigenous people of the giperendekhmichny centers of malaria of tropical Africa a certain pattern in development is observed And. Newborn children are protected from an infection thanks to existence at them of the IgG-antibodies arriving through a placenta from mother. In several months as a result of loss of these antibodies children become very susceptible to malaria, and then gradually gain nek-ry stability. At adult population the high level of antibodies causing considerable restriction of number of parasites and absence a wedge, displays of an infection is observed. Cross And. between separate types, and it is possible, and geographical strains of plasmodiums is absent. The antigenic structure of causative agents of malaria is very difficult, and there are data that in development of an infection there are antigenic options stimulating development of new type of antibodies at each stage.
A trypanosomiasis is also among infections which development is followed by accumulation of humoral antibodys in blood and in cerebrospinal liquid. During the early period makroglobulinovy antibodies prevail, but for the 22nd day antibodies of the class IgG appear though IgM can be found in blood during all infection. Antigenic variability, limits a cut are not set, is especially inherent to trypanosomes of the brucei group that quite often complicates serol, researches at a tsetse-fly disease. Products of antibodies are stimulated by both the somatic, and soluble antigens of trypanosomes which are released at destruction of parasites. Direct dependence between the level of antibodies and intensity of a parasitemia is observed, however at very heavy disease of an antibody can be absent. Assume that action of antibodies consists in disturbance of oxidation-reduction processes of trypanosomes and change of cellular permeability. Possess higher protective action IgG-antibodies and.
Skin and skin and mucous leushmaniosis are characterized by development generally of reactions of the hypersensitivity of the slowed-down type (HSDT) at absence or very low antiserum capacities. And. at these forms of an infection has absolute character and can develop or gradually, becoming full by the period of completion of primary process (Leishmania tropica minor), or more quickly when immunity to a superinvasion steps already on stages of an ulcer (a zoonotic skin leushmaniosis). There are forms of a skin leushmaniosis with hron, a current, not giving in to chemotherapy, at which And. it is suppressed.
At a visceral leushmaniosis in blood high concentration of IgM and IgG whereas reactions of GZT are expressed unequally is observed and develop in different terms after treatment. Antibodies are found already at early stages of an infection and come to light in high credits during all active phase (after successful treatment disappear in several months). Protective action of antibodies is not clear since presence them in high credits in blood does not protect the patient from death. In recent years communication of the immunity acquired after recovery from a visceral leushmaniosis with development of GZT is shown.
At an amebiasis products of antibodies are connected with destruction of amoebas in an organism of the owner since generally cytoplasmatic fraction has antigenic properties. Complexity of an antigenic structure of amoebas and its not identity at the strains of parasites differing on virulence is established. The antibodies which are developed at an amebiasis belong generally to IgG, and they managed to be revealed in blood of the infected animals in high credits during 12 weeks. Along with it already from 1 week of emergence of symptoms of a disease allergic reactions of immediate type whereas reactions of GZT are established only at the long course of an infection develop. Development of resistance to reinfection in the persons who had an amebiasis was not observed, and cases of repeated infections are noted at a high level of antibodies in blood.
Thus, manifestations and mechanisms I. at different protozoan infections are not identical. Deserves attention noted for a number of protozoa (plasmodiums, toxoplasma, a leushmania) the expressed immunodepressive effect concerning the accompanying infections and invasions, the nature to-rogo is not established yet.
The item to arthropod parasites is studied very poorly. It is established, however, that the low-molecular secrets of some species of insects having gaptenny properties at connection with collagen of skin became immunogene. Receipt of secrets causes development of reactions of GZT and GNT (immediate hypersensitivity) which are developed in a certain sequence. It was possible to transfer GZT to a sting of mosquitoes at Guinea pigs by intraperitoneal introduction of lymphoid cells of primed animals.
Features of immunity at children
Immunol, reactivity of a children's organism has the patterns of development in ontogenesis. Is of great importance for the newborn passive And., the presented IgG of mother. It includes various antitoxins, antiviral and antibacterial antibodies. However the newborn has deficit of antibodies to gram-negative microorganisms which do not arrive through a placenta. It creates favorable conditions for development of the corresponding infections. The IgG level of funic serum correlates with contents it at mother, but above because of ability of a fruit to concentrate IgG by active transplacental transport is frequent. This process proceeds most intensively in recent weeks pregnancies therefore the maintenance of IgG at premature subjects is lower, than the term of not wearing out is more. At once after the birth the catabolism of passively received IgG begins, contents to-rogo decreases as much as possible by 6 — 9 months of life.
Maturing of own immune system of the child begins during the early periods of an antenatal life. Lymphocytes of a fruit intensively breed in a thymus gland, from the 12th week of pregnancy they react to phytohemagglutinin, i.e. are functionally active. They support IgM and IgG connected with a surface of lymphocytes. The thymus gland is not only a source of lymphocytes, but also carries out regulation genetically caused immunol. maturing. Immunol, these or those clones of lymphoid cells reach competence at different times. Most early ability to an immune response on antigens of viruses, flagellar antigen of salmonellas, antigen of staphylococcus, some food antigens appears. Penetration of nek-ry amount of antigen through a placenta and pre-natal preparation of lymphoid cells is allowed by antigens of eurysynusic bacteria and viruses. The time difference of emergence of an immune response can be connected also with immaturity of the enzymatic status of the cells which are carrying out roughing-out of antigen.
Functioning of immune system, i.e. synthesis of antibodies and development of an allergy of the slowed-down type, happens only at an antigen challenge. Therefore a push to it is the microbic planting of the newborn coming after the birth. Especially large role is played by the bacteria occupying went. - kish. path. The first immunoglobulin which synthesizes an organism of newborns is IgM. Its contents increases in the first week of life of others earlier (by 1st year) reaches the level inherent to the adult. IgA is synthesized with 2 — 3rd week, raises more slowly and reaches the level of adults by 7 — 12 years. The beginning of synthesis of IgG individually, its synthesis in the 1st month of life, however a catabolism of passively received IgG so is proved exceeds its synthesis that increase in the IgG level begins to be caught only after 2 — 3 months of IgG reaches the same level, as at the adult, after other immunoglobulins. At newborns settling went. - kish. a path microflora conducts to local products of IgA, contents to-rogo in excrements at children of 4 — 6 months approaches that at adults. The maintenance of IgA in a bronchial secret on 1 month of life of the child, on the contrary, very lowly and sharply increases only in the second half of the year of life.
Maturing of immune system can be broken, and its functioning is begun earlier at immunol, the conflicts mother — a fruit and at pre-natal infection of a fruit. In case of infection synthesis of immunoglobulins begins already till the birth. Most clearly synthesis of IgM, level to-rogo higher than 20 mkg / 100 increases the ml is considered as an indirect indicator of a pre-natal infection. At development in the newborn of infectious and inflammatory diseases there is also an increased synthesis of immunoglobulins, especially IgM. Sharply IgM at generalized processes, viral infections raises. Development of an adenoid tissue does not come to an end with the advent of ability to react to antigen at early stages of post-natal development. It proceeds during the entire period of the childhood and comes to an end only in the period of puberty. With age development of an adenoid tissue, accumulation of memory cells, improvement of regulatory mechanisms continues. Steadily intensity of antibodyformation and expressiveness of cellular immunity increases.
Antiorgan antibodies and anti-gamma globulins collect. On process of formation And. the environment, frequency of infectious and inflammatory diseases, preventive inoculations exert impact. Influence of the last on maturing of immune system and its correct functioning is still a little studied. Vaccination shall be individualized and be carried out under control immunol, indicators.
Development of factors hereditary (specific) And. also has the patterns. Their pre-natal synthesis is also limited due to the lack of the corresponding incentives. The exception represents a lysozyme, activity to-rogo is very high in funic serums. Very large number of a lysozyme contains p in amniotic waters. The birth of the child is a powerful incentive and for development of factors hereditary And., which activity sharply increases in the first days of life. An incentive to their products is all complex of the factors connected with change of living conditions of the newborn and causing development of the general adaptation reaction of an organism. Nonspecific protective indicators both at the birth, and within the first weeks of life are lower at premature in comparison with given rise in time. Further dynamics of nonspecific protective factors is not identical. Does not change or a little the maintenance of a complement changes with age. Steadily activity of a lysozyme decreases. After the period of increase as much as possible by 3 years contents properdin begins to decrease and. Nonspecific protective mechanisms are of great importance for children of early age. However their reserve opportunities of mobilization are insufficiently expressedand factors hereditary And. at additional antigenic loading therefore easily there comes their exhaustion. Features of formation And. at the child in many respects define a wedge, the course of infectious, inflammatory, allergic and autoimmune diseases at children.
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P.N. Kosyakov; E. S. Leykina, L. M. Gordeeva (immunity at parasitic diseases), 3. M. Mikhaylova (features of immunity at children).