Mechanisms by which HSCs mobilize into damaged organs are currently under scrutiny.
Macrophage role in these processes is investigated. In this study, we performed a flow cytometry analysis of
CD117+CD38+ and CD117+CD90low HSCs quantity in murine peripheral blood and bone marrow after liver
and kidney injury under stimulation of phagocyte mononuclear system by injection of tamerit. This study have
demonstrated increased levels of CD117+CD38+ HSCs in bone marrow after partial hepatectomy, along with
their migration to peripheral blood in response to tamerit injection. We also demonstrated that peripheral
blood CD117+CD38+ HSCs levels were elevated after kidney injury. After partial hepatectomy, nochanges
of CD117+CD90low HSCs quantity in investigated tissues were detected. We observed increased number of
CD117+CD90low HSCs in murine blood following kidney injury. Thus, we observed different influence of
macrophage stimulation on the quantity of CD117+CD38+ and CD117+CD90low cells. These data suggest
that HSCs mobilization from the bone marrow to peripheral blood depends, at least in part, on phagocyte
mononuclear system, and that macrophage stimulation is important for proliferation and migration of various
HSCs populations following liver and kidney injury.

As assessed by decreased response of ConA-induced blasts to IL-2, a staphylococcal protein A was shown to extract IL-2 from cultural medium after its preincubation with IgG, but it did not bind pure IL-2. Normal human immunoglobulin inhibits reaction of DTH effectors to Listeria antigen, which is also IL-2-dependent. An immunomodulating drug Phosprenyl (sodium polyprenylphosphate) abolishes the inhibitory ffect of immunoglobulin. Since Phosprenyl (as shown earlier) interacts with alpha-chain of rIL-2 and blocks IL-2 activity, the two drugs are in competitive relations. The latter may be explained by identities in prostetic carbohydrate groups of the both glycoproteins (CD25 and immunoglobulin), whereas Phosprenyl and IL-2 would behave like as lectins. These results characterize local conditions and mechanisms of immune regulation under tissue domination of gamma-globulin or antibodies of a given isotype. IgG binds with IL-2, reacting not with an active center but with effector region of IgG molecule, thus blocking IL-2 activity. Since a similar effect is observed under in vivo conditions (in a DTH model), the phenomenon revealed may explein inhibition of immune response after passive injection of antibodies, as well as a feed-back relationship between humoral and cellular immunity. Inhibition of IL-2 biological activity after its interaction with IgG and immune complexes may be considered as a universal mechanism of immune regulation performed by a feedback regulation, which may be influenced by means of Phosprenyl-like immunomodulators. In some infections, malignant growth etc., such mechanism may be of utmost pathogenetic significance. Moreover, such a mechanism cannot be also excluded in some physiological immunogenetic interactions, e.g., in feto-maternal system, where it could promote a positive selection for individuals with broader MHC repertoire, which would be necessary for development of individual and population-based resistance to infections

The aim of the study is to establish the features of expression of GATA-3 in peripheral lymphocytes from bronchial asthma patients (BA). Material and methods. 10 healthy controls, 15 patients with allergic (atopic) and 15 persons with non-allergic BA were examined. A transcription factor GATA-3 expressed in peripheral lymphocytes was analyzed by Western blot after the lymphocytes were lysed. Preparation of cell lysates, and Western blotting were performed by means of a standard procedure (Amersham). An antibody against GATA-3 (Abcam, UK) was used. Levels of the protein were analyzed versus β-actin levels using anti-actin antibody (Sigma Aldrich, USA). Results. Expression of GATA-3 was significantly increased in lymphocytes of patients with allergic BA as compared to healthy persons and non-allergic BA patients. The level of GATA-3 negatively correlated with the degree of airflow obstruction and positively correlated with dosage of parenteral steroids administered. Conclusion. GATA-3 may play a key role in the pathophysiology of BA. One may suggest that increased expression of GATA-3 transcription factor in atopic BA underlie high levels of Th2-cytokines production in allergic disease

Morphology, topography, and immunohistochemical features of leukocyte infiltrates were studied in various sites of the liver samples from the patients with metastatic disease, been affected by hepatitis B and C viruses at different degree of activity. Liver of СВА mice with implanted САО-1 tumour was also under study. Histochemical, and functional features, as well as immune phenotype of these cells were investigated. It has been shown that the major fraction of leukocyte infiltrates, mostly associated with implanted tumours in experimental mice, and in the areas adjacent to the tumor in humans, like as on the peak of viral hepatitis activity, is composed of lymphocytes. They are presented by large numvers of activated proliferating and differentiating cells bearing specific antigens, as well as natural killers and T-lymphocytes, possessing high-level killer activity towards NK-sensitive, and autologous lines of cancer cells. Hence, the results of our study, generally, confirm the data from literature reporting on existence of a special lymphocyte subpopulation, NKT cells, in human or murine liver affected by hepatitis virus or malignant tumors. The data concerning functional properties of these cells may be used for development of immunotherapy methods of viral diseases and oncological conditions complicated by liver metastases.

We have performed a study of cellular and humoral immune parameters in 106 patients with duodenal ulcer working at a chemical plant, and in seventeen healthy persons. The data obtained in this study reveal variable changes in immunity dependent on previous contacts with harmful chemical products (nitrogen compounds).

Antibodies to leukemia differentiation factor (HLDF) in patients with gastrointestinal cancer Abstract. Patients with gastric cancer exhibit higher levels of IgG4-antibodies to human leukemia differentiation factor (HLDF), as compared with healthy individuals, whereas, in patients with colorectal cancer, one may detect high levels of IgA anti-HDLF antibodies, along with lower levels of IgG1 class antibodies against HLDF than in control group. Among patients with gastrointestinal cancer, a positive correlation is revealed between contents of highly differentiated cells in the tumor, and IgM antibodies to HDLF. Meanwhile, a reverse relationship is noted between low differentiation of tumor cells and levels of IgG2 antibodies to HDLF in gastric cancer patients, or IgG3 antibodies to HDLF in patients with colorectal cancer.

 When studying functional features of immune system, a lot of quantitative and functional parameters are determined. A multifactorial analysis allows of detecting interdependent immunological parameters and defining them as significant factors. In present study, four factors are revealed, which are associated with certain clinical characteristics of gastric cancer (tumor invasion depth, lymph node status and distant metastases, tumor stage, histological type). The data obtained are of interest, with regard of systemic approach to functional studies of immune functions.

Distinct data concerning DNA cytometry of peripheral blood populations are relatively scarce, including oncopathological conditions. Among tasks of present work, we evaluated effects of malignancies upon functional state of peripheral blood cells and determination of correlations between cell ploidy, cell cycle kinetics and parameters of immune system.

It was revealed, that, in blood samples of the patients with autoimmune thyroid diseases, serum antibodies against cell-free fraction of Bifidobacterium bifidum 791 and Lactobacillus plantarum B-01 were detected, respectively, in 71 and 63% of cases, that being two-fold higher than appropriate frequencies in healthy blood donors. An evidence was obtained that presence of some components specifically reacting with autoantibodies against thyroid peroxidase and thyroglobulin on the surface of the microorganisms cells and competing for binding of these immunoglobulins with thyroid antigens. One may also suggest a presence of bacterial components, interacting with thyroid peroxidase. The data obtained let us suggest that probiotic microorganisms of Bifidobacterium and Lactobacillus genus could take part in pathogenesis of autoimmune thyroid diseases, by means of molecular mimicry mechanisms.

Results of study of immunoprotective properties of medicine Salmozan and its combined effect with probiotic bacteria of genus Lactobacillus оп natural resistance and parameters of adaptive immunity of experimental animals аге presented. Salmozan stimulates production of IL-1α, IL-12, TNFα in peritoneal macrophages, production of MIF in реуеr patch and spleen cells and, thus, activates Th1 cells and cytotoxic T cells. Bacteria of Lactobacillus genus enhance modulating effects of Salmozan оn cellular immune reactions. Results of the experiments carried out provide the basis for conclusion abont stimulation of anti-infection and anticancer immunity bу Salmozan which саn bе used fог immunoprophylaxis and соrrеction of cellular immune reactions bу means of probiotic therapy.

During last years, a role of genetic factors in maturation of innate immunity functions was actively studied. It is known, that some SNP in TLR9 and TLR2 genes are known to be associated with development of infection in pregnancy. However, interrelations of various TLR-mediated anti-infectious mechanisms with genetic factors in pregnant women were poorly studied. The aim of present study was to evaluate associations between the following SNPs: Arg677Trp, Arg753Gln of TLR2 gene, A2848G SNP of TLR9 gene, and frequencies of pre-term birth complicated by infections in Russian population of Moscow City. SNPs Arg677Trp, Arg753Gln in TLR2 gene have been studied in a clinical material by means of PCR-RFLP analysis, using AciI restrictase. A2848G polymorphic marker in TLR9 gene was assessed by real-time PCR, employing TaqMan probes. It has been shown, that Arg allele of Arg753Gln TLR2 gene was associated with urogenital infections. When studying A2848G polymorphism in TLR9 gene, the A Allele was associated with normal delivery, thus assuming the A2848G polymorphic marker as a protective one.

Genotypes CD14 gene genotypes frequencies of in control group and in group of patients with nosocomial pneumonia (NP) correspond to Hardy-Weinberg law. We revealed a statistically significant increase of genotype Т/Т frequency in the patients with NP (33.33%) in contrast to control group (18.09%) (р = 0.008). Notable is a difference in severity of NP cours in the patients with C/С, C/Т and Т/Т genotypes. In first case, the score of discase severity, using CPIS scale, was 7.81±1.32, whereas in second case it was 8.93±1.48 (р < 0.05). A positive correlation was found between resolution time of NP and CD14 genotype, i.e. Т/Т genotype was associated with prolonged respiratory support in NP with mecanical ventilation, as compared with NP cases in the patlents with C/С and C/Т genotypes (r = 0.70; р = 0.01). It was shown that the patients with CD14 Т/Т genotype exhibited hypercytokinemia due to TNFα. IL-1β and IL-1RN, thus pointing to a key role of CD14 gene polymorphism in immune pathogenesis of NP.

The aspects of autoimmune thyroiditis (AIT) remain quite actual, since many issues of etiology, pathogenesis, morphology, classification, diagnostics, therapy and prediction of this disorder are far from final solution. Since disturbances of fine molecular immune mechanisms underlie pathogenesis of either immune disorder, the genes coding its main components, are regarded as potential candidate genes predisposing for AIT, e.g., genes of surface antigen (CTLA-4) and protein tyrosine phosphatase non-receptor 22 (PTPN-22). We have performed genotyping of 298 Tatar women in Tatar Republic (Russia) with respect to age and biochemical parameters (control group, 137 persons; AIT group, 161 patients). The following gene polymorphisms were tested: +49 А/G, -318 С/Т, -1661 А/G of СТLA-4 gene, and 1858 С/Т polymorphism of PTPN-22 gene. Genotyрing was performed by PCR-RFLP method as described earlier. The data were analyzed using Chi-square test and 95% confidential interval (CI). The frequencies of CTLA-4 -1661 G allele and genotype A/G and +49 G/A G allele and genotype GG carriers were significantly higher in AIT patients than in controls (P = 0.04, OR 1.84, 95% CI 2.31-1.4; P = 0.001, OR 2,0 95% CI 1.62-2.31 respectively), with increased contents of serum antibodies to thyroglobulin (OR, 1.56, 95% CI 2.25-3.6; OR 1.12, 95% CI 1.9-2.75, respectively) and to thyroperoxidase (OR 1.3, 95% CI 1.5-4.1 for G/G genotype of +49 A/G polymorphism), independently of age (р < 0,05). We showed that the combinations of A/G, T/C and G/G genotypes of -1661 A/G, -318 T/C and +49 G/A polymorphisms is associated with increased risk of genetic predisposition to ITD in Tatar women (OR 7.87, 95% CI 2.03-3.25). A strong association was also observed between the increased level of antibodies to TPO (> 1000 ME/l) and GG genotype of +49 G/A polymorphism (OR 1.3, 95% CI 1.5-4.1) and antibodies to TG (> 100 ME/l) and genotypes A/G and G/G of CTLA-4 -1661 A/G and +49 G/A polymorphisms (OR 1.56, 95% CI 2.25-3.6; OR 1.12, 95% CI 1.9-2.75, respectively), independently of age. The genotypes -318 T/C and 1858 T/C of CTLA-4 and PTPN-22 genes, respectively, are not associated with AITD in Tatar women (p > 0.05). Our results suggest that polymorphisms of CTLA-4 and PTPN-22 genes may modify individual susceptibility to autoimmune thyroiditis in Tatar women.

Antigenic profiles of envelope glycoproteins of hepatitis C virus presented by three genotypes 1b, 2a/2c and 3a, which are most widespread in the territory of Russia and, in particular, in Novosibirsk, were studied using a panel of overlapping synthetic peptides. It was shown that highly immunogenic peptide epitopes of Е1 and Е2 proteins common for all HCV genotypes, are located in amino acid positions 250-260, 315-325 (Е1 protein), 390-400 (hypervariable region 1), 430-440, and 680-690 (Е2 protein). The greatest inter-genotypic differences were recorded in positions 280-290, 410-430 and 520-540. A novel antigenic determinant was detected in the region of aa 280-290 of the Е1 protein which was typical only for HCV 2a/2c genotype. A broad variation in the boundaries for the most epitopes suggests a high variability of the Е1 and Е2 viral proteins; however, a similar repertoire of antibodies induced by different HCV genotypes indicates to an opportunity of designing a new generation of cross-reactive HCV vaccines based on mapping of the E1 and E2 antigenic regions.

When performing ultrasonography of thymus in young children, we have revealed a specific phenomenon, i.e., a significant increase of thymus size in the children of 4 to 6 months old, having been observed at the terms of vaccination with a combined dyphteria/pertussis/tetanus (DPT) vaccine. After examining the dimensions, volume, mass and features of thymic blood flow, we have found that, during the DTP vaccinations, 88.7% of the children exhibit an increase in thymic dimensions, along with higher blood flow rates, as compared with the same indices in unvaccinated children. In 11.3% per cent of the cases, the vascularization of thymus was not altered at all, or did not show any changes. To our mind, these ultrasonic parameters of thymic status represent a regular reaction of a key immune organ to a challenge with bacterial antigens, i.e., being an indicator of the primary immune response to DTP vaccination.

CD95 (Fas/APO-1) antigen expression was studied on the surface of neutrophil granulocytes from cervical secretions. Sixty-five female patients with established Chlamydia infection were found to have an increased CD95+ antigen expression following basic therapy. CD95+ receptors on neutrophils in the patients with Chlamydia infection have been shown to return to normal levels following a combined magnetic laser treatment.

In patients with diffuse toxic goiter (DTG), relative numbers of CD4+, CD8+ lymphocytes, activated T-lymphocytes (CD3+HLA-DR+) proved to be increased, whereas absolute contents of T-independent (CD3-CD16+CD56+), and T-dependent (CD3+CD16+CD56+) NK-cells were found to be decreased. Moreover, IgA and IgM levels were decreased among DTG patients. In most DTG cases, amounts of lymphocyte-to-platelet agregates were sharply decreased. Studying parameters of immunogram, lymphocyte-platelet adhesion allows of assessing specific changes of adaptive immune response in diffuse toxic goiter.

The goal of present work was to study main cell subpopulations of immune system, frequency of human herpes virus (HSV) type 1 activation, and presence of HSV in patients with tuberculosis (TB). We have shown an increased level of herpesvirus type 1 and type 2 manifestation in patients with different types of tuberculosis (TB). A statistically significant decrease in the CD4/CD8 ratio and in percentage of CD3+, CD4+ cells patients with certain clinical forms of TB was shown, as compared to the group with active HSV infection. The data obtained showed absence of correlation between TB-related reactions, HSV infection, and levels of HSV-specific antibodies. Deficient function of cells with natural killer (NK) activity, and decreased numbers of CD56+ cells have been also of shown. NK cells may be among most relevant components of immune reactions to HSV infection. Main role in HSV activation in the TB patients depends on deficiency of NK-like cells.

Serum immunoglobulin A, M, G сontents, specific antibodies and circulating immune complexes were studied in 278 patients with acute, subacute and chronic brucellosis (resp., 84, 98 and 96 cases). Significantly increased levels of serum immunoglobulins, specific antibodies and circulating immune complexes are found in various clinical forms of brucellosis. Serum contents of IgA, M, G and circulating immune complexes did not depend on clinical stage of brucellosis. Higher levels of specific antibodies, as determined by agglutination and hemagglutination reactions, were detected in acute and sub-acute brucellosis.

The patients with autoimmune thyroiditis and various functional states of thyroid gland, and diffuse toxic goiter with pronounced thyrotoxicosis were studied for neurospecific enolase and enolase-specific autoantibodies levels in blood serum. Increased concentrations of neurospecific enolase and specific autoantibodies were revealed in all groups of the patients. A conclusion was drawn that nervous system may be involved into pathological process during development of thyropaties.

We present a clinical case of a viral intrauterine infection in an infant with certain combination of CD14, TLR2, TLR6 gene polymorphisms. A possible mechanism is proposed for development of fatal outcome in such prenatal infections.

Serum levels of myelin basic protein (MBP)-bound immune complexes were studied in blood sera from women with gestosis, as compared with those in normal pregnancy and non-pregnant woman. The amounts of IgG-MBP complex in blood serum were determined by enzyme immunoassay using isolated anti-МBP-antibodies. The study has shown that about 0.05 mcg of IgG ml of blood serum are associated with myelin basic protein in unpregnant women or in normal pregnancy. Mild gestosis is accompanied by a 2-3-fold increase in MBP immunocomplex concentrations in blood serum. More severe stages of gestosis are characterized by its further rise, thus achieving maximal values of such MBP immune complexes (0.8 mcg/ml) in patients with pre-eclampsia and eclampsia. Their amounts were reduced twice after the periods of eclampsia. Serum levels of MBP-bound IgGs may be used to determine severity of gestosis and to predict a risk of eclampsia in pregnant women.