Pavel Gurevich

An immunohistochemical study of the secretory immune system in human fetal membranes and decidua of the first trimester of pregnancy.

Problem: We analyzed the presence and distribution of components of the secretory immune system (SIS) in human fetal membranes (amnion, yolk sac, chorion) and decidua from the first trimester of pregnancy.

Pathology of lymphoid organs in low birth weight infants subjected to antigen-related diseases: A morphological and morphometric study

&NA; The pathology of lymphoid organs in 38 low birth weight (LBW) human infants has been evaluated by morphological and morphometric features. The gestational ages of infants ranged from 22 to 32 wks and their age at death varied from 1 hr to 153 days post partum. Infants were divided into 3 groups: 1) without antigenic effects, 2) with mild (bronchopneumonia), and 3) with severe antigenic effects, mainly sepsis. In mildly affected LBW infants, the fetal type of the immune reaction was found. It continued during the period studied (till 5 mths) and was manifested in the reaction of macrophages and the transformation of lymphocytes to lymphoblasts. Reactive centres of follicles and mature plasmocytes were not found. During the first months of postnatal development, an increase in the amount of lymphocytes in the lymphoid organs and in the rate of proliferation of reticular epithelium and a decrease in the area of the cortex in the thymus were found in all infants. In severely affected infants, the number and the size of follicles in the spleen decreased significantly and the total number of cells decreased more than 3 times. Similar changes were found in lymph nodes. These changes as well as the weak reaction of the thymus are the main features of the insufficiency and fast devastation of the lymphoid system. A compensatory increase in the number of neutrophils and eosinophils in the red pulp of the spleen and lymph nodes was found after the second week.Abbreviations: LBW, low birth weight; HMD, hyaline membrane disease; RDS, respiratory distress syndrome; LN, lymph node; AI, accidental involution of thymus; TC, thymic corpuscles.

Immunoglobulin A in the epithelium of the respiratory tract and intrahepatic bile ducts of fetuses and newborns with pneumonia and sepsis

The level of different immunoglobulins (IgA, IgG, IgM) in the tissues of 28 late fetuses and newborns was studied with peroxidase-labeled monoclonal antibodies. IgA+ and IgM+ lymphocytes were found in the spleen, lymph nodes and sometimes in the liver. IgG+ lymphocytes were not found. A high level of IgA+ material was found in the epithelium of the trachea, the epithelium and submucosal glands of the bronchi, but not the bronchioles, and in the epithelium of hepatic bile ducts and in their lumina. Such IgA is considered to be secretory--sIgA. Secretory IgA-containing epithelial cells appeared at 20 to 21 weeks of gestation; their number increased from 2.5 cells/10,000 microns2 in 23- to 26-week-old fetuses, to 8 cells/10,000 microns2 in 36- to 40-week-old fetuses. Secretory IgG and IgM were not detected. In fetuses with pneumonia or sepsis, the number of IgM+ and IgA+ lymphocytes increased significantly. IgM+ lymphocytes appeared not only in the spleen and lymph nodes, but also in the lungs. In such cases, the number of sIgA-containing epithelial cells in the trachea, bronchi and intrahepatic bile ducts decreased, sometimes completely disappearing. The amount of IgA+ material in the lumina of these organs increased, reflecting an intensification of sIgA secretion during infections. The presence of a marked amount of sIgA in fetuses from week 20 of gestation is considered to reflect the high importance of this immunoglobulin against normal contamination by microbes after birth, and to evidence the early maturation of the immune system.

Comparative study of the role of serum levels of p53 antigen and its tumor cell concentration in colon cancer detection

The role of serum levels of p53 antigen in detection of colon cancer was studied in different groups of cancer and noncancer patients and was compared with the results of immunohistochemical analyses. The p53 antigen was isolated from the human serum as a cytoplasmic fraction using the recently described new type of columns for affinity chromatography, gel fiberglass columns (Zusman and Zusman, 1995). Its concentration was detected by high performance liquid chromatography. The serum level of the p53 antigen significantly increased in cancer patients (3.6 mg ml(-1)) as compared to its concentration in patients with benign tumors (1.7 mg ml(-1)) or in patients with noncancer disorders (0.49 mg ml(-1)), and this was found to be a result of higher concentration of p53 protein in tumor cells. Coefficient of correlation between cellular concentration of p53 protein and its serum level was 0.44 in noncancer lesions and 0.48 in cancer patients. Serum levels of p53 antigen was shown to be highly active either in patients with noncancer lesions or in patients with cancer (r = 0.46 and 0.51 respectively), whereas the cell determination of p53 protein was effective only among noncancer patients (r = 0.61) but not in cancer patients (r = 0.22). The findings suggests that serum determination of p53 antigen can perhaps reveal this oncoprotein already in the early stages of cancer or even predict the putative development of cancer. The possibility to use the serum-levels of p53 antigen in the follow up patients with chronic diseases and to detect transformation of these diseases into cancer, or monitoring former cancer patients in order to detect as early as possible the incidence of recurrent cancer is discussed.

Pathology of Lymphoid Organs in Low-Birth-Weight Human Fetuses Subjected to Antigen-Induced Influences: A Morphological and Morphometric Study

To evaluate the pathology of lymphoid organs in low-birth-weight (LBW) human fetuses obtained after premature birth, morphological and morphometric features were studied. The ages of fetuses ranged from 22 to 32 weeks and their weights from 400 to 1180 g. In fetuses at 22-23 weeks without antigenic effects, the lymphoid organs were seen to be well developed and their differentiation was similar to that of full-term fetuses. In older unaffected fetuses (up to 32 weeks), a significant increase in size of the lymphoid organs and a rise in the rate of the differentiation of lymphoid cells were observed. Fetuses exposed to antigen-related diseases underwent morphological changes in lymphoid organs presumably as a consequence of the primary fetal immune reaction. These changes were characterized by a high increase in the number of lymphoblasts and partly of macrophages in the spleen and lymph nodes. Reactive centers in spleen follicles and in lymph nodes, and plasmocytes in all the lymphoid organs, were absent. The main reaction to severe antigenic influences was decompensation of the lymphoid organs manifested morphologically by their devastation as a result of a decrease in the number of small lymphocytes and, in severe cases, of lymphoblasts and macrophages. Exposure of fetuses to antigen-related diseases thus appears to cause marked changes in the normal ontogenesis of lymphoid organs.

Secretory Component, J Chain, and Immunoglobulins in Human Embryos and Fetuses of the First Trimester of Pregnancy: Immunohistochemical Study

In our previous studies, we described the development of the secretory (mucosal) immune system (SIS) in human fetuses in the second trimester of pregnancy. In the present study, we examined the presence and distribution of components of this system in human embryos and early fetuses in the first trimester. An immunohistochemical study was performed on 17 embryos and 9 fetuses (4 to 12 wk of development) using antibodies against secretory component (SC), joining (J) chain, immunoglobulins (IgA, IgM, IgG), subsets of T and B lymphocytes, and macrophages. Cells positive for SC, J chain, and IgG were found in epithelial tissues from wk 4 of pregnancy. In the internal organs, such as the myocardium and endocardium, capillary endothelium, epithelium of the kidney tubules and some others, only J chain and immunoglobulins were seen. IgA was weakly reactive in tissues where SC and/or J chain were presented. IgM was very weak or absent. Among the cellular components of the SIS, only macrophages were seen in 4-wk-old embryos. CD3+ and CD20+ lymphocytes were found at wk 7 to 8. IgA- and IgM-positive lymphocytes appeared at the end of wk 9. The SIS is widespread in embryonic and early fetal periods and begins to function before the appearance of the common immune system in the developing organism. The first functional components of the SIS, such as IgG and IgA observed in this study, are most probably of maternal origin.

The role of the fetal immune system in the pathogenesis of RhD-hemolytic disease of newborns

Data in the literature and authors research regarding the role of the immune reaction of fetuses and newborns in the pathogenesis of RhD conflict and hemolytic disease of newborns was analyzed. In this disease, the immune response of fetuses and newborns is shown to develop under the effects of maternal antigens, including RhD IgG, which cross the placenta. One of the results is the formation of immune complexes (ICs) between the maternal antigens and fetal IgM. In the intensive immune reaction, these ICs are removed from the infants at a high rate. As a result, the intensity of erythrocyte destruction, the degree of anemia and hyperbilirubinemia decrease. Various forms of HDN are of different intrauterine duration: from a few days in the icteric form without anemia to a month or more, in the hydropic form. In the latter form, decompensation of the immune system develops; extravascular erythroclasia by macrophages is replaced by intravascular lysis of erythrocytes. We suggest some methods to determine the fetal condition and a cure for the most severe cases of HDN, as well as a way of decreasing RhD-sensitization in women. These suggestions may be of interest to specialists in pediatrics and obstetrics and may be of clinical use.

The Placental Barrier in Allogenic Immune Conflict in Spontaneous Early Abortions: Immunohistochemical and Morphological Study

Morphologic changes in the placental barrier in spontaneous early abortions under the maternal‐embryonic immune conflict, and the role of maternal immunoglobulins (Igs) in these changes.

Immunoprotection of gonads and genital tracts in human embryos and fetuses: immunohistochemical study.

PROBLEM: The immune protection of genital organs in embryogenesis has not been sufficiently studied. The purpose of this study was to investigate the development of the secretory immune system (SIS) in the gonads and genital tracts of human embryos and fetuses.
 MATERIALS AND METHODS: Developing gonads at different stages and genital tracts from 18 embryos and 39 fetuses in the first to third trimester of gestation were analyzed for presence of different component of SIS: secretory component (SC), joining (J) chain, IgA, IgM, IgG, macrophages, and subsets of lymphocytes. The material was divided into two groups: cases not subjected to foreign antigenic effects (group I, n=31) and those under antigenic attack (chorioamnionitis, group II, n=26).
 RESULTS: In embryos and fetuses of group I, SC, J chain, and IgG were seen in the epithelium of mesonephric and paramesonephric ducts, proliferating coelomic epithelium, epithelium of the uterine tubes and uterus, epithelium of the vas deferens, epididymis, and rete testis. IgA and IgM appeared in 6‐week‐old embryos. J chain, IgA, IgM, and IgG, but not SC, were found in the primary oocytes and oogonia, spermatogonia, and interstitial cells. An abundance of macrophages was seen in 4‐week‐old embryos. T and B lymphocytes first appeared in 6–7‐week‐old embryos. In embryos and fetuses of group II, reactivity of immunoglobulins (Igs) decreased until they disappeared altogether.
 CONCLUSIONS: Components of SIS were seen in genital organs in 4–5‐week‐old embryos and were present during the whole intrauterine period. We suggest the presence of two forms of immune protection of fetal genital organs. One form contains SC, J chain, and Igs and is present in the genital tract epithelium. The second form contains only J chain and Igs and is present in germ cells of gonads. The loss of Igs in cases with chorioamnionitis reflects the functional participation of the SIS of genital organs in response to antigen attack.

Pathomorphologic and immunohistochemical study on the devastation of rat embryos by antiphospholipid antibody positive serum.

Problem  While relying on previous publications, our aim was to examine the morphologic changes, induced in early rat embryos by intra‐uterine exposure to the low‐molecular weight fraction of boiled human serum containing antiphospholipid antibodies (APLA) that had been obtained from women with antiphospholipid syndrome (APS).