IMMUNOLOGY OF THE EMBRYOGENESIS (Latin immunis free, saved from something + grech, logos the doctrine; grech, embryon growing in another a germ + genesis an origin) — the section of immunology studying processes of formation of an antigenic structure of fabrics and bodies during embryonic development, pattern of formation of an immune responsiveness in ontogenesis and immunological relationship of an organism of mother and a fruit. Experimental embryology, the main task a cut — studying of mechanisms of regulation of processes of growth and a differentiation of fabrics (see. Embryology experimental ), includes And. aa. as organic part. Methods I. aa. are used in the analysis of interaction of a kernel and cytoplasm, during the studying of the phenomena of embryonic induction, competence and determination. K I. aa. closely the researches on regeneration and a metaplasia of fabrics which are carried out using immunol, methods adjoin. The results received during the experiments on And. aa., are widely used in a number of the fields of theoretical and applied medicine. Such problems immunology (see), as biosynthesis of antibodies, autoimmune reactions and immunol, tolerance (see. unresponsiveness ), cannot successfully develop without corresponding immunoembriol. researches.
And. aa. arose and was created in close connection with development of the general (noninfectious) immunology. Also. I. Mechnikov, studying immunol, the relations in the developing organism, established that they play an active role in processes of a morphogenesis of the lowest vertebrata. Further attempts to apply immunol, methods to the analysis of processes of embryonic development are connected with original researches II. L. Krichevsky (1914), E. S. Geronimus and sotr. (1937), Shekhtmana (A. M. of Schechtman, 1948), O. E. Vyazova (1952), Vurdeman (M. of W. Woerdeman, 1955), Tyler (A. Tyler, 1955), P. N. Kosyakova (1962), G. I. It is Abelian (1963), etc. Gradually immunol, the researches conducted in an experimental embriol. aspect, led to accumulation of big actual material about antigenic properties of fabrics of germs of the person and animals, about dynamics of formation of an antigenic structure of the developing bodies and systems (antigens of blood serum, heart, liver, kidney, lung, brain, tissues of an eye and other bodies), about developments in an embryogenesis of ability to answer antigenic irritation with specific cellular or humoral reactions.
Genetic determination of processes organ and a histogenesis is shown at the level of synthesis of specific proteins which can be revealed with the help immunol, methods. In this regard studying of the sequence of emergence in laying of body of specific antigens supplies with the valuable information on the general patterns of processes of activation (derepression) of those genes which manages development of the studied systems of fabrics.
The uniform, standard classification of antigens of embryonal fabrics and bodies does not exist. B. V. Konyukhov (1958) and Island E. Vyazov (1962) divide antigens of the developing organism into three groups: the species-specific antigens which are present at fabrics at all stages of development and reflecting specific specificity of the studied proteins; organ (fabrics) the specific antigens arising at certain stages of development and remaining at all subsequent stages; the stadiospetsifichesky antigens characteristic only of certain periods of development and disappearing during a further differentiation. Along with the term «stadiospetsifichesky antigen» the terms «stage-specific antigens» are used [Mack Naas and Clark (G. W. Ms of Nace, W. M of Clarke), 1958], «embryonic (embriospetsifichesky) antigens».
For designation of group antigens (see), specific to many bodies, but absent in blood serum the terms «all-organ antigens» (Shekhtman, 1948), «interorgan antigens» (V. M. Barabanov, 1966) and «heteroorgan antigens» are offered (Olenov, 1970).
Are fullestly studied in immunoembriol. the plan of tissue of eye and kidneys, being convenient model for embriol, researches. The data obtained at the same time in principle are similar to results of studying of antigenic properties of other fabrics and bodies of vertebrata, including and the person.
The ground mass of water-soluble antigens of lens of vertebrata is presented by crystallins — the high-molecular proteins consisting of subunits. Several classes of crystallins (пре-α, α, β, γ, δ-crystallins)))))))))), antigens, heterogeneous on set, are known. The majority of crystallins belongs to strictly organ-specific antigens of a crystalline lens. At the same time in lens of vertebrata in insignificant quantity interorgan antigens come to light.
Formation of the antigens specific to a crystalline lens is analyzed generally in experiences on germs of amphibians and birds. The crystalline lens of mammals, including and the person, is less studied in this respect.
Organ-specific antigens of a crystalline lens are found at early stages of an organogenesis of vertebrata — at a stage of formation of a lenticular bubble or during an initial stage of formation of primary fibers. During further formation of a crystalline lens the gradual complication of its antigenic structure proceeding generally as an anaboly is noted. Along with emergence in a certain sequence everything new and new antigens of a crystalline lens occurs natural complication of set of the subunits making them. It is characteristic that during an antigenic differentiation of a crystalline lens the first there are not organospetsifichesky, but interorgan lenticular antigens. A similar sort data were obtained during the studying of antigens of other important part of an eye — retinas. The retina of hens differs in complex antigenic structure and contains the serum-born antigens, interorgan antigens of wide specificity, antigens inherent only to tissues of an eye and brain, and an organ-specific antigen.
The first in the developing retina of chicken embryos there are interorgan antigens of wide specificity inherent to many body tissues. Formation of these antigens matches on time the period of formation of an eyeglobe and precedes a histogenesis of a retina. The organ-specific antigen of a retina and antigens characteristic only of a retina, an iris and a brain, come to light at later stages of development — in the period of expressed gistol, differentiations of this fabric.
Existence of organ-specific antigens of a kidney is finally proved in the 30th 20 century. In a kidney the majority of antigens belongs to interorgan and only the small number has strict organ specificity. Antigens of a mesonephros appear at a stage of the small differentiated nephrogenic fabric. Then in process of development of a mesonephros in it there are all new and new antigens. However from the beginning fiziol, destructions of a mesonephros the quantity and concentration of the antigens found in it sharply decrease. The next period of an organogenesis of a kidney — a stage of a metanephros — is characterized again by gradual increase in a range of fabric renal antigens and strengthening of some of them. As a result by the end of embryonic development at a kidney there are almost all fabric antigens inherent to definitivny body.
As well as in process of other bodies, during the formation of a kidney first of all there are interorgan antigens and only at much advanced stages gistol, differentiations of fabrics of this body appear organ-specific antigens. At rather early stages of an embryogenesis (in the person on 7 — 10th week of pre-natal development) in the developing renal fabric also stadiospetsifichesky antigens inherent only to certain phases of an organogenesis of a kidney are found. The nature and exact localization of these antigens are still unknown.
Parallelism in morfol, and antigenic differentiations, and also increase in degree of organ specificity during an organogenesis was led to the assumption that the fabric antigens which are synthesized in the developing rudiment exert a certain regulating impact on further process of formation of body. O. E. Vyazov and V. M. Barabanov (1973) made a hypothesis that interorgan antigens with a wide range of fabric specificity create in cells of the developing body necessary conditions for activation (derepression) of the genes controlling formation «next» morfol, structures and synthesis of antigens, highly specific for this body. In studying of antigenic properties of an organism of a germ
also researches of patterns of formation in an embryogenesis of the person and animal isoantigens of cells and proteins of a blood plasma are of special interest (see. Blood groups ). Consider that formation of isoantigens of the known genetic systems of blood groups of the person begins in the early embryonal period. Isoantigens (And yes In) the AB0 systems can be found in erythrocytes on 5 — 6th week of embryonic development. Antigens A and B at newborn children are expressed more weakly, than at adults. After the birth activity of these antigens gradually increases, reaching a maximum by 5 — 10 years. Formation of O(H) of antigen happens at later stages of embryonic development in comparison with antigens A and B. Antigens (M and N) the MNSs systems are found in erythrocytes of 7 weeks embryos, however agglyutinabelny properties of these erythrocytes are less expressed, than at erythrocytes of adults. Since 3-month age, antigens M and N of erythrocytes of an embryo do not differ from M and N antigens of the adult. Formation of antigens of system a Rhesus factor also belongs to early embryonic development.
In particular, D, S and E antigens accurately come to light at fruits of the person on 10 — 14th week of development. During the same period of an embryogenesis there are antigens of other genetic systems of blood of the person; by the end of the 3rd month of an antenatal life most of them is rather eumorphic (P. N. Kosyakov, 1965).
Studying of leukocytic and platelet antigens at the person is begun rather recently, and in literature there are no accurate data on formation of these isoantigens in an embryogenesis. It is obvious that emergence of a number of leukocytic alloantigens is dated for quite early period of development. In particular, alloantigens of leukocytes of the HLA system are found in a spleen, a liver, lungs and kidneys of fruits of the person of 3 — 5 lunar months.
The long time existed idea of total absence in the developing germ of active synthesis of antibodies (specific immunoglobulins). And it is valid, in the period of an embryogenesis at birds and some species of mammals (rabbits, pigs) ability to answer with development of specific antibodies administration of antigens does not develop yet. Synthesis of antibodies manages to be found in these animal species for the first time in the early post-natal period of development and only on condition of administration of antigens by it in a complex with adjuvants. At the same time it is characteristic that newborns of a krolchat, pigs, Guinea pigs if synthesize antibodies to proteinaceous antigens, then in incomparably weaker degree, than mature animals.
Contrary to these animal species germs of cattle, sheep, opossums and primacies are capable to develop the circulating antibodies already during pre-natal development. Ability to answer with synthesis of specific antibodies administration of antigen arises at fruits of sheep, dogs and monkeys at various stages of an embryogenesis and depends on a dose and character of antigen. It is not excluded that character of an immune response of fruits is defined on different antigens by existence or absence at them the corresponding clones of lymphoid cells. Fruits of mammal and newborn children, just as at adult individuals, at the beginning of antibodyformation have IgM and only after IgG. In particular, the born in time or premature children already have ability to form antibodies to certain antigens, and these antibodies belong to IgM. There are data that antibody formation at a fruit of the person can be a consequence of pre-natal infection with a virus of a rubella, syphilis or toxoplasmosis.
The trace number of IgG can be found in blood serum of a fruit of the person at the end of the first half of pregnancy. Their concentration gradually increases, reaching at newborns of the level determined in blood serum of mothers or even exceeding it. It is shown that at the person these immunoglobulins (IgG, but not IgM) get into blood of a fruit through a placenta from mother. However by means of autoradio graphical and immunofluorescent graphical methods in cultures of a spleen of 20 weeks fruits of the person low, but reliable synthesis own not only IgM, but also IgG is found. In blood of a fruit in the same terms of development the number of IgG-and IgM-positive (in reaction of an immunofluorescence) cells was revealed a nek-swarm. Intensity of process of synthesis of immunoglobulins in an organism of a fruit is insignificant, and the main number of IgG of the newborn arrives transplatsentarno from mother, and colostrum is the main source of IgM.
Maternal antibodies upon their transplacental transition to a fruit inhibit at it ability to development of own antibodies. It, perhaps, difficulty of detection of ability of a fruit to independent antibodyformation speaks. The mechanism of such inhibition is still not clear. Perhaps, the antibodies entered into an organism (as well as collecting during antibodyformation) regulate synthesis of own antibodies through a feedback mechanism.
At some animal species (a chicken, a mouse, a rat) cellular reactions of immunity form by the time of hatching or the birth. On the other hand, at the person newborn and premature children are already capable to show the expressed reaction of rejection of allotransplant. A similar sort ability was found also in fruits of a rabbit after the 22nd day of pre-natal development. Fruits of sheep are capable to tear away allotransplants for the 80th day of pregnancy, i.e. at the very beginning of its second half. Change of a transplant to this term did not lead to development defined immunol, reactions at fruits. It is essential that at fruits of sheep ability to react against allotransplants developed after acquisition by them of ability to develop antibodies to a nek-eye to antigens. Fruits of monkeys (Masasa of rhesus) are capable to tear away allotransplants in earlier terms of development, than fruits of sheep. So, a number of authors noted rejection of cells of marrow and leather of adult monkeys M.'s fruit of rhesus on 58 — the 63rd day of pregnancy (lasting pregnancy of 165 days). At the same time at a fruit the sensitization to allotransplant of mother can develop and, on the contrary, there can be no disturbances normal immunol, relationship of an organism of mother and a fruit.
Thus, ability to answer humoral and cellular immunol, reactions to antigenic irritation is already inherent in the organisms which are at rather early stages of ontogenesis.
Researches on And. aa., carried out in the medicobiological plan, allowed to save up extensive material about processes which provide performance of generative function of the person. Methods I. aa. are applied in the analysis of hormonal regulation of a reproductive cycle and pregnancy, and also mechanisms of fertilization and implantation of an ovum, interactions of a fruit and organism of mother. In competence I. aa. studying of a pathogeny of the inborn diseases caused by disturbances immunol, relationship in the «mother — a fruit» system enters.
Development and successful use sensitive and highly specific radioimmunol. methods allowed to obtain essentially important data on a role of separate hormones of a hypophysis in regulation of function of male and female gonads. In particular, with the help radioimmunol. methods it is established that products of follicle-stimulating (FSG) and luteinizing (LG) of hormones of a hypophysis are controlled by the same rileasing-factor of a hypothalamus. The blocking method of FSG and LG specific antibodies allowed to deepen significantly our ideas of value of these hormones in regulation of functions of gonads of the person (see. Oogenesis , Sex hormones , Spermatogenesis ).
The increasing relevance in medicobiological aspect is acquired by researches of antigens of sex cells and their role in emergence of various forms of male and female infertility. In spermatozoa of the person organ-specific antigens and antigens of blood groups are found species-specific, interorgan. Some of these antigens are responsible for education at women of specific spermoimmobiliziruyushchy antibodies. Existence in blood serum of the antibodies causing an immobilization of spermatozoa is in close correlation connection with infertility of not established etiology at women.
As it was revealed in experiences on Guinea pigs, spermoimmobiliziruyushchy antibodies can pass from blood serum into secrets of a sexual path of females. Antibodies to spermatozoa were also found in blood serum of sheep and cattle. Credits of such antibodies are much higher in blood serum at infertile females.
On the other hand, the analysis of an antigenic structure of ovaries and ova allowed to identify a specific antigen of zona pellucida. Blockade of this antigen the corresponding antibodies leads to impossibility of fertilization of an ovum spermatozoa or to disturbance of normal implantation already of an oospore. These data, and also results of a research of tkanespetsifichesky antigens of a placenta and a uterus of pregnant women closely brought closer us to creation effective immunol, a method of abortion [E. Diczfalusy, 1974].
One of important practical issues in which development immunoembrnolog take part is the problem immunol, relationship of mother and a fruit. Practically in all cases of pregnancy mother and a fruit differ from each other on the of antigens and between them can arise immunol. relationship like reaction of the recipient against allotransplant. However in most cases immunol, the relationship developing in the course of pregnancy between organisms of mother and a fruit does not outgrow in immunol, the conflict. The reason of it immunol, a paradox is not found out yet. In this regard the following assumptions express: the organism of a fruit did not ripen in the antigenic relation; the organism of mother immunological is inert during pregnancy; the uterus is immunol. the exclusive place in an organism of mother; protection of a fruit against influence immunol. factors of an organism of mother it is connected with existence of a barrier between mother and a fruit. The hypothesis of «a biological barrier» uses the greatest recognition, the role to-rogo is carried out by a placenta (JI. S. Volkova, 1970; O. E. Vyazov, M. Sh. Verbitsky, 1972). Some researchers consider that the analysis of an isoantigenic (AB0) differentiation of fabric of a placenta, fetal membranes and an amniotic fluid will help to get closer to understanding of a role of a placenta in implementation of the specified function (L. S. Volkova, 1970). Despite nek-ry inconsistency of data, it is possible to consider established that the decidua contains And - and the B-antigens characteristic of blood of mother; amnion and an amniotic fluid — AB0 isoantigens of a fruit. In fabric of chorion of the group antigens which are available in blood of a fruit and in amnion it is not revealed. It is supposed that antigens of amnion and an amniotic fluid connect maternal antibodies and do not allow them in an organism of a fruit in cases of incompatible pregnancy.
The role immunol, a barrier which prevents immunization of mother transplant isoantigens of a fruit or protects a fruit from reaction of mother directed against these antigens can carry out a trophoblast. However the question of an isoantigenic differentiation of a trophoblast is studied insufficiently. In literature there are only single messages on availability of Rh (D) isoantigen in a syncytial layer of fibers of chorion and on lack of some HLA isoantigens in a syntrophoblast of a placenta of the person.
The normal placenta is not a barrier, absolutely not permeable for cells, and the person has some exchange of cells between organisms of mother and a fruit. The large number of observations with use of various markers about transition of erythrocytes, leukocytes and thrombocytes of mother to a fruit and in the opposite direction — blood cells of a fruit in an organism of mother is saved up. Transition of cells of a fruit to mother can cause in it a condition of isoimmunization or tolerance to antigens of a fruit of a fatherly origin. What of these states will develop, depends on a variety of reasons among which a certain value has quantity of the cells of a fruit which got to mother.
Thus, in spite of the fact that between mother and a fruit exists biol, the barrier preserving them against mutual damage between them there can be during pregnancy immunol, interactions. It is not excluded that immunol, reactions take part in providing the normal course of implantation processes and childbirth, and the perversion of these reactions can lead to disturbance of pregnancy.
As a result immunol, the conflict between organisms of mother and a fruit there are such forms of obstetric and pediatric pathology as usual abortions, premature births, a hemolitic disease of newborns, toxicoses of pregnancy etc. Along with obstetricians and pediatricians immunoembryologists are directly involved in studying of a pathogeny, methods of treatment and prevention of this group of diseases. One of the most well studied manifestations immunol. the conflict in system mother — the fruit is hemolitic disease of newborns (see). At the person the hemolitic disease of newborns arises in connection with incompatibility of mother and a fruit on isoantigens of blood groups, and most often in the conditions of Rho(D) - and AB0 incompatibility. The method of immunoprevention R h of a hemolitic disease of newborns which allows to prevent development a Rhesus factor sensitization at primapara Rh-negative women by introduction by it in a puerperal period of antirezusny immunoglobulin — anti-Rho(D) IgG is offered. Use of this method in clinic showed that at repeated pregnancies at the women «protected» after first labor by drug of antirezusny globulin Rh antibodies are not developed and healthy Rh-positive children without symptoms of a hemolitic disease of newborns are born.
Because at Rh-negative women, sensibilized earlier as a result of transfusion of Rho-positive blood or the previous pregnancies, this method of prevention of a hemolitic disease of newborns cannot be applied, researches on development of adequate pilot models of a hemolitic disease of newborns on which it would be possible to approve new methods of treatment and prevention of this disease were begun.
In the Soviet Union the models of a hemolitic disease of newborns on rats and monkeys (baboons hamadryads) which allowed to approve a method of preventive treatment of a hemolitic disease of newborns are for the first time developed. The principle of creation in an amniotic fluid of a fruit of an artificial barrier from haptens which connect arriving to a fruit from antibodies and mother is the basis, preventing destruction of erythrocytes and other cells of the developing organism. As haptens serve phosphatides (erythrophosphatides) emitted from erythrocytes of blood of baboons hamadryads (M. Sh. Verbitsky, etc., 1972). Successful results of approbation of this method on monkeys allow to hope that it will be used further for antenatal treatment of a hemolitic disease of newborns at the person.
See also Embryology .
Bibliography: Averkina R. F. and Vyazov O. E. Studying of an antigenic structure of tissues of kidney of the person, Bulletin Ekspery, biol, and medical, No. 6, page 92, 1969; Brondz B. D. Cellular bases of immune recognition, Predecessors T-antigen-svyazyvagoshchikh and B-lymphocytes and pattern of their maturing, Ontogenesis, t. 8, No. 3, page 211, 1977, bibliogr.; P. N jambs. Isoantigens and isoantibodies of the person it is normal also of pathology, M., 1974, bibliogr.; Fundamentals of immunoembryology, under the editorship of O. E. Vyazov and V. M. Barabanov, M., 1973, bibliogr.; Tumanov A. K. Serumal systems of blood, M., 1968, bibliogr.; In about u of s J. Isoelectric focusing of lens crystalline, in book: Progr, isoelectric focusing and isotachophoresis, ed. by P. G. Righetti. p. 235, N. Y., 1975; Clayton R. M. Problems of differentiation in the vertebrate lens, in book: Current topics develop, biol., ed. by A. A. Mos-cona a. A. Monroy, v. 5, p. 115, N. Y. — L., 1970, bibliogr.; Clayton R. M. Comparative aspects of lens proteins, in book: The eye, ed. bv H. Davson a. L. Graham, v. 5, p. 400, N. Y. — L., 1974; Cooper E. L. Comparative immunology, L., 1976; Immunological approaches to fertility control, ed. by E. Diczfalusy, p. 13, Copenhagen, 1975.
Lake of E. Elms, A. T. Mikhaylov.