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Horizontal transfer of genes between viruses and their hosts played an important role in the evolution of various eukaryotes including contemporary mammals as well as the pathogens themselves. Elements of viruses of various types can be found in the genome of animals. Endogenous retroviral elements composing up to 8% of human genome length not only determine its high flexibility and rapid adaptation potential. Many of virus genes such as Fv1, Lv1, Lv2 being analogues of capsid and other proteins determine effective suppression of viral replication after cell penetration by the causative agent. Introduction of these elements into genome of a wide variety of animals from fish to primates could have taken place against the background of global natural cataclysms of viral origin. Integration of retrovirus genes coding surface glycoproteins with immunosuppressing domains into genetic apparatus of animals served as an impetus to the development of viviparity and spread ofplacental mammals. Their cell analogs syncytins perform a dual function: take direct part in the formation of syncytiotrophoblast layer of placenta and ensure tolerance of immune system of mother to embryo. The acquisition of cell genes by viruses also played an important role in their evolution: various interleukins and other modulators of immune response introduced into viral genome from cell genetic apparatus became one of the most important factors of pathogenicity of a wide variety of causative agents including poxviruses, cytomegalovirus, Epstein-Barr virus and many others. Evolutionary pathways of the virus and host are thus inseparable from each other, and character of one of these directions is largely dictated by the vector of another.

The expression of VEGF and membrane-bound and soluble forms of the VEGF-R1 receptor in cultured placental macrophages (trimesters I and III of pregnancy) was studied by flow cytometry, cytometric bead array, and ELISA. Nearly all population of placental macrophages (98%) was capable of producing VEGF during the early and late gestational periods. However, the expression of cellular VEGF-R1 varied from 3.4 to 92%. VEGF secretion was relatively low in the first and third trimesters (0.5 and 1.1 pg/10(5) cells, respectively). Cultured placental macrophages produced soluble receptor sVEGF-R1 in the first and third trimesters (86.4 and 36.4 pg/10(5) cells, respectively). Stimulation with LPS was followed by a 4-fold increase in sVEGF-R1 secretion. Our results indicate that placental macrophages are involved in the autocrine and paracrine regulation in chorionic villi. The data suggest that these cells have a physiological and pathogenetic role in gestation.

Modern molecular biological studies have significantly improved understanding of structural and functional organization of the female reproductive system. The paper gives a brief overview of the literature and own research on verification and expression in the endometrium and placenta of many peptides, biogenic amines, steroids, cytokines and other signalling molecules, which, acting as hormones, enzymes, inhibitors, receptors, growth factors, immunoregulatory agents, transport's and binding proteins, provide the local regulation of intercellular neuroimmunoendocrine relationships that play a key role in the mechanisms of human embryogenesis and reproduction.

The placenta is a specific organ of extracorporeal immunity. It has a tissue-blood barrier that protects a developing fetus against infectious agents. Owing to this, placental infection is not fatal to a fetus and always falls far short of intrauterine infection. Fetal inflammatory diseases occur in immune defects and placental morphological barrier damages.

The immune-competent cells of placenta play the important role in protection of developing fetus against infectious agents; but their dysfunction can lead to development of placental insufficiency that affects health both fetus and mother. The aim of this study was the comparative analysis of presence of immune competent cells in villous chorion of mature placenta, taken from women with diabetes of different age groups. In our study we found three subpopulations of immune cells in villous chorion of mature placenta: natural killer cells (NK), B-lymphocytes and macrophages. Prevailing subpopulation are macrophages, they are detected 1,8 times more often than B-lymphocytes, and 2,3 times more often than NK. The quantity of immune competent cells in groups with diabetes of various types is different. Thus, the greatest number of macrophages was detected in group with diabetes type II of middle age (29-35 years)-- 4.62 +/- 0.93%, B-lymphocytes in group of women with diabetes type I of younger age (18-28 years)--2.50 +/- 0.30%, NK-cells in group with diabetes type I of younger age--1.98 +/- 0,42%. Analysis of received data showed the differences in expression of markers of immune cells in women of different age groups, which brings about the conclusion of various reactance of immune system of women with diabetes depending on age.

Evidence for possible mechanisms providing maternal immune system tolerance to fetoplacental structure during physiological pregnancy is presented. Conditions forming systemic and peripheral tolerance are considered. Major regulatory cell and molecules are defined that are directly involved in tolerance realization to fetal antigens. In addition, processes of T-lymphocyte extra-thymic differentiation and apoptosis-inducing placental ligands are examined as essential mechanisms maintaining tolerance.

The main aim of this work was to determinate a role of placental macrophages in aetiology of gestosis and significance of pregnant women age during this pathology. We analyzed expression of CD68 (marker of placental macrophages) in placentas of healthy women and women with gestosis from younger and older age groups. We have found that in case of gestosis the increasing expression of placental macrophages at placentas of women younger than 30 years old takes place, although at placentas of women older than 30 years old expression of macrophages remains at stably high level during normal pregnancy flow and in case of gestosis.

Pathological immune complexes (PIC) are revealed in high percent (100%) of cases by placental immunomorphological studies in insulin-dependent tissue. This leads to the development of an immunopathological process in the placental tissue. Parallel electron microscopy shows that some placental vessels are in close contact with the basal membrane of syncytiotrophoblast. PIC deposition in the area of confluence of the basal membranes of a syncytiotrophoblast and the vascular endothelium, which act as filters, results in the destruction of the basal membranes to rupture formation, causing the transplacental transport of substances together with immune complexes in the form of endocytotic vacuoles from the intervillous lacuna directly to the vessel. Active proliferation of vascular endotheliocyes leads to typical angiopathy as the body's defense reaction.

Examination of 15 autopsies of puerperas who died in the first postpartum days has identified the pathomorphological and immunohistochemical signs differentiating labor sepsis from the other type - postpartum sepsis. Labor sepsis that runs typically of a systemic inflammatory reaction is characterized by initial antenatal inflammation of the fetal membranes and placenta with the latter's immunoimaging of granulocytes, macrophages, plasma cells, and tumor necrosis factor. Moreover, labor sepsis runs in the presence of suppressed cellular and humoral immunity in the spleen and lymph nodes. The relative intact pattern of the uterine endo- and myometrium is retained with generalization of an inflammatory reaction along the organs. The pathologist who analyzes female pyoinflammatory diseases in the postpartum period should meticulously investigate all placental components in addition to a puerpera's organs.

Immune inflammation is a typical pathophysiological process caused by exogenous and endogenous factors. Fibrinoid necrosis and cell infiltrations are the morphological features of tissue lesion caused by immune inflammation. Tissue lesion in immune inflammation may be connected with immune complex (IC) formation or T-cell aggression. Lesion caused by antigen-antibody complexes develops as a result of direct IC formation in the tissue or their inflow from microcirculation. Potential sources of IC in the placenta are maternal blood flow, the formation of IC between maternal antibodies (AB) and embryonic antigens, and IC formation in fetal blood vessels. After sedimentation in the placenta, circulating IC can cross syncytiotrophoblast tissue with the participation of specific receptors to immunoglobulin Fc-fragment. The process of antifetal AB formation may start in the maternal organism, as a result of which it forms AB to embryonic and placental antigens, including paternal Rh, ABO, and HLA, and some trophoblast antigens. IC are able to initiate inflammatory process through interaction with the compliment system, through the activation of macrophages excreting cytokines (TNF-alpha and IL-1), and through influencing basophiles and thrombocytes (the liberation of vasoactive amines). Gestosis is associated with system inflammatory response with endothelial dysfunction as the main element. As the clinical features of gestosis do not develop before 20 weeks of pregnancy, its clinical manifestation is preceded by increased fetal blood-brain barrier permeability, elevation of the level of neurospecific proteins of fetal origin in maternal circulation, and the formation of specific IC causing acute endotheliosis.

Object of the investigation - estimation of changes of the feto-placental complex and syncytiotrophoblaston based on the placental morphology and the activity of the antiviral antibodies in expectant mothers. The work is based on findings from 50 expectant mothers with cytomegalovirus (CMV) infection - 43 with reactivation of the latent infection according to the data of high avid IgG (86%) and 7 with primary active CMV infection according the level of the low avid IgG (14%). 20 healthy expectant mothers were included in the control group. It was shown that the active primary and reactivated CMV infection accompanied by the drawing in pathologic process the chorion structures in a productive inflammation - chorionamnionis and choriovillusitis manner, which testify to drawing the fetus immune system in reciprocal reaction with subsequent intrauterine growth retardation.

Placental macrophages (Kashchenko-Hofbauer cells) belong to a special population of tissue macrophages of human fetal provisional organs. The aim of the present study was to investigate the structure of Kashchenko-Hofbauer cells at the stage of placenta formation using the methods of light and electron microscopy and immunocytochemistry. Cytological and cytochemical peculiarities of Kashchenko-Hofbauer cells revealed in this study, leave no doubt that they belong to the tissue macrophages group. Their cytoplasm is strongly reactive with antibodies against CD68 lysosomal antigen suggesting potentially high phagocytic activity of these cells. Weak nuclear labeling with proliferation marker PCNA was found in placental macrophages.

The effect of ascending infection of birth-ways on transport of maternal immunoglobulins (Igs) through the placental barrier in humans during the first trimester of pregnancy was studied. The transport of Igs is seen already in 3.5-to 5-week-old embryos, and different cellular and biochemical compounds participate at each stage of this process. Transport of Igs through the trophoblast is carried out due to the secretory component (SC) and, perhaps, to some other receptors. Monocytes together with Igs penetrate into capillaries between the endothelial cells and are transported with the blood all over the body. It seems that SC and other receptors help Igs to penetrate into capillaries through the endothelium. Further, Igs are transported with erythroblasts. In the development without infection the transport of IgG was seen in all cases studied. Inflammation of the birth-ways is accompanied by an increase in transport of all Igs, already in early embryogenesis. Three groups were distinguished: 1) abortions without inflammation; 2) cases with signs of moderate inflammation (endometritis, deciduitis); 3) cases with intensive inflammation with necrosis and leucocytic infiltration. Transport of Igs was seen in 77.8% cases of the first group and in all cases of groups 2 and 3. Transport of IgM was not found in the first group, but was seen in 50% cases of group 2 and 66.7% of group 3.

The main reasons of fetus loss as observed in pregnant women with chronic viral infection are discussed in the paper. The role of the immune system and different mechanisms of endothelial lesions inherent in the genesis of the discussed phenomenon are analyzed. An approach to management of pregnancy in patients with viral infections targeted at the prevention of pregnancy complications is suggested on the basis of the analysis and independent authors' observations.

The paper deals with different aspects of the relationships occurring between the pregnant woman and the fetus having paternal antigens. Analysis of a great deal of recent information clearly indicates that local uterine immunity plays a great role during pregnancy. The specific features of the gene expression of major histocompatibility by an invasive trophoblast and the immunosuppressive function of placental fibrinoid are discussed. A detailed account of the immunocompetent cells, including T lymphocytes, giant granular lymphocytes, and macrophages, that are involved in immunological responsiveness within the decidua is given.

20 uteri, 80 placentas and the hearts of 66 normal fetuses from rheumatic mothers have been studied. Exacerbations of rheumatism were observed in some mothers during pregnancy. Sclerosis with enhanced synthesis of collagen type I, III, IV, V and fibronectin was observed in ECM when rheumatism during the pregnancy was not active. Activation of rheumatism during the pregnancy was followed by disturbances of synthesis of interstitial and membrane collagen types, alteration of stromal-parenchymatous relations and development of dyschronosis in the placenta and fetal heart. The study of the heart from children aged 3 months-14 years showed a long-term effect of maternal rheumatism.

Indirect criteria of the value of the immune placenta barrier in case of a large foetus are distinguished: relatively small volume of the fibrinoid substance, moderate synthesis by the syncytial epithelium of glucosaminoproteoglycans (GAPG), slight lymphoplasma cell infiltrates with a marked suppressor influence, the lack of antigens HLA = Dr on the trophoblast and formation of the adequate interrelation ship between the immune dependent placental structure and the thymus of the large foetus this allowing to retain the foetus up to 38-40 weeks or even more. In case of delay in the intrauterine foetus development there is a sharp increase of the fibrinoid substance, focal enhancement of GAPG production by the syncytial cells, decrease of the suppressor activity and the appearance in some cases in the trophoblast of antigens to HLA=Dr this being probably the manifestation of a premature exhaustion of compensatory-adaptive reactions in the placenta.

Analysis of publications dealing with infectious pathology of placenta is performed. Placentitis of different etiology and different routes of contamination have specific features. The incidence of viral and mycoplasma etiology with intracellular multiplication of the agent is considerably higher than of bacterial or other placentitis with extracellular multiplication. The incidence of placentitis is considerably higher than that of intrauterine infection. Placenta is an organ of immune protection of the organism and is capable to produce both specific and non-specific immunity factors.

Serial measurements of allo- and autoimmune lymphocytotoxic antibodies (LCT-AB), circulating immune complexes (CIC) and heterophilic hemolysins were carried out over pregnancy weeks 24-40 in 63 pregnant women with small-for-date fetuses, 63 ones with other pregnancy complications, and in 15 ones with normal pregnancy. The mean allo- and auto-LCT-AB levels remained unchanged over the course of pregnancy and were virtually the same in all the examinees. CIC and heterophilic hemolysin levels were found growing in women with small-for-date fetuses starting from pregnancy week 28, as against the two reference groups. A direct relationship between abnormally high heterophilic hemolysin levels and blood rheology disorders could be traced. The incidence of unfavorable perinatal outcomes was increasing if heterophilic hemolysin levels surpassed 1.1 U optic density and the placenta was thin. These results permit considering the small-for-date fetus syndrome as a manifestation of immunity conflict in pregnancy.

An investigation of 88 placentas in toxicosis of the second half of pregnancy has detected symptoms of the immune alteration detailed by means of an electron microscopic analysis and immunomorphological investigations with the help of luminescent sera against immunoglobulins A, M. G and C3 fraction of complement. The alterations found are indicative of the participation of immune mechanisms in the formation of placental insufficiency and their important role in pathogenesis of gestational toxicosis.

Biological activity of 110 series of commercial gamma-globulin preparations was studied; they were found to contain placental antigens, group-specific blood substances, gonadotropic hormones and antibodies to them. Placental antigens were found in 12% of placental and abortive gamma-globulin batches in titres of 1 : 2--1 : 16; no placental protein was revealed in donor gamma-globulin. There were group-specific blood substances in all the batches of placental and abortive gamma-globulin studied (in titres of 1 : 138--A, 1 : 112 B in the placental gamma-globulin and in titres of 1 : 48.9--A, 1 : 32--B in the abortive gamma-globulin). In the preparations from the venous blood group-specific substances were either absent or present in lowe titres only (1 : 2). The value of gonadotropic hormones in the placental gamma-globulin batches constituted 873+/-157, and in the abortive--991.4+/-147 IU/l; no gonadotropins were revealed in donor gamma-globulin. The mean titres of antibodies to gonadotropin hormone in the gamma-globulin preparations made of placental blood constituted 1 : 236+/-32, of abortive--1 : 131+/-16.6, and of the venous blood--1 : 46+/-24.7. The presence of biologically-active substances in the gamma-globulin preparations pointed to the necessity of increased requirement of their quality; additional requirements to its standardization proved to be also necessary.

A comparative study of the content of serum protein antigens in 156 batches of human immunoglobulin preparations, produced from placental material and donor plasma in the USSR and Bulgaria, has been made by means of immune electrophoresis. The results thus obtained indicate that immunoelectrophoretic analysis may be used for the additional characteristic of the antigenic structure of immunoglobulin preparations, as well as for evaluating the degree of the purification of immunoglobulin from nonspecific serum proteins in the process of the production of commercial preparations.

It has been demonstrated that pregnancy-specific beta1-globulin is synthesized by the rat placenta. Other organs of pregnant animals (liver, kidneys, lungs, heart, spleen) were incapable of synthesizing this antigen. The greatest amount of pregnancy-specific beta1-globulin is observed in the blood of intact animals on the 11th day after the introduction of ground placental tissue.

The content of trophoblastic beta-globulin in 142 lots of commercial immunoglobulin preparations from 20 manufacturers, produced from placental, abortion and donor blood sera, has been studied. 83% of lots from abortion blood serum and 94% of lots from placental blood serum have been found to contain the admixture of this beta-globulin, its concentration in the lots from placental blood serum being significantly higher. The method for the detection of trophoblastic beta-globulin may be used for evaluating the quality of immunoglobulin preparations as it indicates the degree of their purification from placental proteins.

Gonadotropic activity of 106 series of immunoglobulin preparations obtained in the USSR and-the People's Republic of Bulgaria was studied. In difference from donor immunoglobulins, all the preparations of placental materials were contaminated with chorionic gonadotropin. Gonadotropin content in the immunoglobulins made of abortion serum was 2--7 times greater than in the preparations from the retoplacental serum and the placental extracts. The mean results of gonadotropin content in the immunoglobulins obtained by biological studies differed from those obtained from the investigations by immunological methods since the mentioned methods apparently characterized different properties of the hormonal molecule.

The report deals with studies of the penetration of gamma-globulin I131 of rabbit antibrain sera into the different brain areas of intact and sensitized rats and into the placenta of embryo tissues. It was demonstrated that lebeled I131 gamma-globulin containing antibodies to homo- and heterologous brain may in a small amount penetrate from the blood into the CNS of animals. The authors demonstrated as well that labelled antibodies penetrated from the blood of pregnant rats through the placenta and accumulated in the brain and internal organs of the embryo. These facts are significant for development of pathogenesis of an antenatal brain pathology.

A simple, practically feasible method based on neutralization of viruses with antibodies present in pools of placental immunoglobulin followed by their reactivation from the complex has been proposed for objective evaluation of the protection of the population against circulating variants of influenza virus and preliminary assessment of their antigenic novelty. The data obtained by this method show that the study may be done within a comparatively short period and will give an objective evaluation of the antigenic novelty and epidemic importance of various influenza virus strains with reference to the immunological status of the population in a definite region which permits one not only to determine the epidemic hazard of the strains for the present time but also to prognosticate it for the future.

It has been demonstrated that placenta extract of rats contains up to 14 antigens. Moreover, 11 of them are interorgan proteins of wide and limited specificity, two antigens (alpha 1- and alpha 2-globulins) are attributed to acute-phase proteins typical for pregnancy. beta 1-Globulin is a specific protein of rat placenta. The content of these antigens in blood serum increases with pregnancy and reaches a maximum toward the delivery; 3-4 days after delivery beta 1-globulin disappears completely from maternal blood, whereas the concentration of acute-phase proteins drops to the initial level.

Data are presented on the spleen and thymus structure, time of appearance of the lymphocytes and their heterogeneity in the liver, thymus, spleen, lymph nodes and blood of human foetuses with hemochorial placenta (3 to 34 weeks) and of the minipigs foetuses with epitheliochorial placenta (32 to 95 days). In both foetuses the first T- and B-lymphocytes are found in liver, T-lymphocytes are then found in thymus and later in spleen and lymph nodes whereas B-lymphocytes are found, after liver, in spleen. Kinetics of T- and B-lymphocytes during embryogenesis is described. Reaction of the minipig lymphocytes to mitogens was demonstrated.

The experiment has demonstrated a higher immunosuppressive activity of antilymphocytic serum, purified with the use of a placental immunoadsorbent, in comparison with the preparations exhausted by red blood cells and plasma. This fact experimentally substantiates the use of the immunoadsorbent prepared from human placenta for the purification of antilymphocytic immunoglobin preparations. Rabbit immunoglobulin to human lymphocytes obtained by means of the new method corresponds to the technical specifications for such preparations and is less reactogenic than antilymphocytic immunoglobulin prepared in accordance with the routine technology.

A tissue-specific basement membrane-associated protein has been identified by the use of monoclonal antibodies prepared against a protein fraction of human placenta. In frozen sections of human tissues the monoclonal antibodies decorated basement membranes of Schwann cells, striated muscle, and trophoblast. In antibody-affinity chromatography of limited pepsin digests of human placenta, a 65-kDa polypeptide was bound by the monoclonal antibodies. Polyclonal antisera and new monoclonal antibodies were raised against the isolated 65-kDa polypeptide, and they stained human tissues identically to the original monoclonal antibodies. An 80-kDa polypeptide was detected by these antibodies in placental extracts prepared without proteolysis. The 65-kDa and 80-kDa polypeptides were immunologically distinct from laminin, type IV collagen, fibronectin and major serum proteins. These polypeptides are presumably derived from a novel basement membrane-associated protein which we named merosin. Several cDNA clones were isolated which code for a protein specifically recognized by polyclonal antibodies to the 65-kDa fragment. In developing mouse tissues, merosin was first detected at the newborn stage. The restricted tissue distribution and the late development appearance of merosin suggest that the protein has a tissue-specific function in highly differentiated cells.

Data are presented indicating that 1 ml of 10% and 1% immunoglobulin possessed similar epidemiological activity in the prophylaxis of infectious hepatitis. It was shown that redical action of infectious hepatitis on the epidemic process was possible only in case of embracement by immunoglobulin vaccination of not less than 80% of children aged from 1 to 11 years. The economic effect of the introduction of 1% immunoglobulin constituted about 40 000 roubles per 100 000 persons vaccinated. Besides, a possibility of side-effects were nilin case of placental immunoglobulin since in the 1% preparation nonspecific biologically active substances could penetrate in much lesser amounts.