Abstract. In pregnancy, mutual cell exchange proceeds between mother and foetus. Therefore, a great research interest is connected with phenomenon of specific influence of non-inherited parental HLA upon various immune reactions in the offspring. This article deals with possible mechanisms of influence of non-inherited parental HLA upon development of immunocompetence in foetus and child, including examples from transplantation, autoimmune pathology, and partial immunodefiencies.

Abstract. The review considers contemporary data concerning the mechanisms of interaction between infectious agents and host immune system. The ways for evasion of the host immune reactions are described, and “behavioral” patterns are provided for particular pathogens, e.g., viruses, bacteria, protozoa, helminthes. The diversity of cells and soluble mediators participating in the immune response is discussed.

Abstract. Conformational changes of human serum γ-globulin were studied during and after its binding with copper and zinc ions, using molecular ultrafiltration and differential spectrophotometry. The contents of nonbound metals in the filtrate were evaluated, resp., with sodium diethyl thyocarbamate and o-phenanthroline. It has been shown that copper and zinc exhibited common biological properties during their interactions with protein, but the binding differed sufficiently under similar experimental conditions. E.g., it was confirmed that copper was more active at the external sites of γ-globulin molecule, whereas zinc demonstrated tropicity for the areas of protein intraglobular compartments. The metal-binding sites have been described that differ in their parameters of interactions with cations and their spatial location within globular domains. Approaches are suggested for dynamic analysis of saturation for these differently located sites by the metal ions. We discuss the issues of altered conformational state of the γ-globulin molecule during the binding of cations, as well as potential usage of these data in clinical immunology.

Abstract. In former studies, using an experimental rabbit model of acute post-streptococcal glomerulonephritis (GAS), we have proven a role of M-like Fc-binding streptococcal proteins (IgG FcBPs) for initiating destructive/degenerative lesions of renal glomeruli that are characteristic to membranous/proliferative and destructive glomerulonephritis. This activity was shown for the strains of types 1, 22 and 49. Their clinical isolates are able to bind Fc fragment of human and rabbit IgG, and are considered as an etiological agent of glomerulonephritis. It is well known that GAS strains of M12 serotype (commonly nephritogenic) are not able to interact with IgG monomers, and usually bind aggregated IgG, in spite of participation of IgG FcBPs in the both events.

In present study, the GAS reference strain M12(1800) and twenty-one clinical strains of M12 type isolated from the patients with acute poststreptococcal glomerulonephritis (APSGN) were tested for binding with two artificial immune complexes (ICs): (i) peroxidase – antiperoxidase rabbit IgG (PAP) and (ii) tetanus toxoid – anti-tetanus human IgG (TAT). Streptococcal strain M12 (1800), as well as the majority of clinical isolates (19 strains) were strongly positive for the binding of both ICs tested. Using previously described model of experimental streptococcal glomerulonephritis rabbits were injected with heat-killed M12(1800) and each of two clinical isolates M12(257) and M12(305), positive and negative for the binding of ICs, respectively. Renal tissue material of rabbits injected with M12(1800) and M12(257), but not M12(305), showed strong inflammatory and degenerative changes compatible with pattern observed in APSGN. Streptococcal strains M12(1800) and M12(257), in contrast to strain M12(305), induced circulating anti-IgG, tissue deposition of IgG and C3 as well as secretion of IL-1β, Il-6 and TNF-α by the glomerular mesangial and endothelial cells. Our experimental data suggest that the IC-binding ability of type M12 streptococci should be of importance for the nephritogenic potential of these GAS serotype strains.

Abstract. Activation levels of hypothalamic structures (AHN, PVH, DMH, VMH, LHA, PH) were analyzed within first hours after injection of antigens [lipopolysaccharide (LPS) and bovine serum albumine [BSA]). For all investigated hypothalamic structures, an increase of c-Fos positive cells numbers was observed after injection of the antigens, as compared to the controls. LPS injection caused activation of more multiple neuron populations. AHN, PVH, LHA, and PH structures exhibited the highest levels of c-Fos activation upon LPS application. BSA injection induced activation of lesser cells quantities, but their enrichment in c-Fos protein was higher, thus resulting into increased optical density of VMH, LHA and PH neurons. Hence, the present work has shown that activation pattern of hypothalamic structures differs upon application of antigens that are different by their origin.

Abstract. Specific autoantibodies against acetylated, maleylated and malonic dialdehyde-(MDA)-modified lipoproteins are detectable in human plasma. Immunization of rabbits with autologous, correspondingly modified low-density lipoproteins (LDLs) did induce autoantibodies against acetylated, maleylated and MDA-modified lipoproteins. In atherosclerotic lesions from hyman aorta, the epitopes have been detected that were recognized by the antibodies to acetylated, maleylated, and MDA-modified LDLs. Such antigens were detected at all atherogenesis stages, beginning with the earliest lesions (lipid spots), and their deposition pattern was quite variable.

Rabbit and human autoantibodies against acetylated, maleylated and MDA-modified lipoproteins recognized antigens in human atherosclerotic aorta. Modified proteins were localized both intra- and extracellular in tectum, superficial and deep layers of the atherosclerotic lesions. The most typical mode of depositions for all modified proteins si represented by extracellular deposits in the cap of lipid streaks and fibrous plaques, especially in transitional “shoulder” area.

The intimal deposits of modified proteins shared similar features with distribution of apo-B-containing lipoproteins, like as of lipids detectable by Oil Red staining. The areas where modified proteins and apo-B-containing lipoproteins were revealed did often coincide with foci of IgG deposits. Modified proteins were not detectable in the non-affected segments of aortic intima.

Abstract. The study deals with p34 distribution in tissue and sera from the patients with breast cancer, using Western-blotting with МКА 1F3-2D4 monoclonals and antisera that identified p34 in breast cancer tissue samples, in metastases. In blood sera, p51-53, p150-p250 were assayed. The proteins may be associated either with cathepsin D precursors, or mucins, or cadherins, or CD22 adhesion molecule.

Abstract. The levels of autoantibodies (AAbs) to double- and single-stranded DNA were studied in blood serum of sixty-one patients with hemorrhagic fever complicated by renal syndrome (HFRS), and twenty-five healthy persons using ELISA technique. In 95% of HFRS patients, the AAb levels to native (double-stranded) DNA were close to their values in healthy group (resp., 0,02-0,26 vs 0,06-0,27 arbitrary units). The levels of AAbs to single-stranded level in serum of patients significantly exceeded the threshold values for healthy persons (resp., 0,37-0,80 vs 0,14-0,57 arbitrary units). The average levels of AAbs to single-stranded DNA in the patients were increased twice, in comparison with normal values. These results demonstrate that hantavirus infection followed by development of HFRS are accompanied by activation of autoimmune processes in the organism, being associated with increased synthesis of AAbs to denatured DNA. AAbs to denatured DNA autoantibodies may participate in inflammatory destruction of kidney glomerular capillaries in HFRS.

Abstract. Establishment of basic processes leading to differences in immune response at genetic level occurs in the course of studying associations between certain polymorphic alleles, as well as evaluation of correlations between the haplotypes of cytokine genes, and specific protein production in vitro. The features of association between main parameters of humoral and cellular immunity, as well as levels of pro-inflammatory (TNFA и IL2) and anti-inflammatory (IL4 и IL10) cytokines with allelic variants of promoter regions of the mentioned genes were analyzed in HIV-infected patients, as compared with healthy Russian population of Caucasoid origin. In present work, we have performed genotyping, along with evaluation of humoral and cellular immunity, in 127 HIV-infected patients, and 52 donors served as a control group. To determine spontaneous and ConA-stimulated cytokine production in some patients, ELISA technique was used for assays with conditioned media from mononuclear cells. From the data obtained one may be inferred, that 308А TNFA, -330Т IL2, -592А IL10 alleles are more characteristic to the HIV-infected patients with decreased cellular pro-inflammatory component of immunity, and increased activity of B-cell immunity, in comparison with persons carrying other gene variants. In general, it should be stressed that the mentioned genes variants may determine general susceptibility for more severe course of disease, exerting some pleiotropic action upon some pathogenetically important parameters of HIV.

Abstract. The aim of present study was to determine levels of IL-1β and its inhibitor, IL-1ra in blood serum and bronchoalveolar lavage fluid (BALF) of 20 patients with COPD, depending on severity of their disease, activity of inflammatory process, bacterial and viral complication. Methods. Twenty male patients with COPD (stage 2 to 4) were examined. It was shown that all the patients with COPD displayed high levels of IL-1β, both in the area of inflammation, and in blood serum. The latter index was dependent on the severity of disease and activity of inflammatory process. In BALF, the contents of IL-1β in all the patients under study was significantly exceeded the normal levels of this cytokine even at the earliest stages of evolving COPD. concentration in serum was depended at stage of disease and activity of inflammatory procces. There were no differences in IL-1β concentrations in BALF of 2 - 4 stage COPD patients. IL-1ra levels in the patients’ serum were within normal levels, and tended to increase in BAL, thus causing imbalanced IL-1ra/IL-1β ratio both in the inflammatory area, as well as systemically. The maximal detection of respiratory pathogens did significantly correlate with decreased IL-1ra/ IL-1β ratio, thus confirming the data on infectious agents as a pathogenetic component in COPD.

Abstract. The group of patients in amount 45 person received the standard combined therapy by preparations of recombinant IFN-α in combination with ribavirin. The positive effect of standard antivirus treatment at patients with chronic HCV-infection associated with increase of level of IL-2, decrease of levels of TNF-α, IL-1α, IL-12р40, IL-12р70 and IL-10 in peripheral serum. It has allowed to use them as noninvasive markers of the steady virologic answer during treatment of a chronic HCV-infection.

Abstract. Recurrent respiratory papillomatosis (RRP) is the most frequently occurring tumour of the upper airways associated with a human papilloma virus (HPV). The aim of this study was to reveal some features of systemic and local immunity in RRP, to investigate clinical and immunological efficiency of local treatment with recombinant interferon-α (rIFNα), and to determine clinical and laboratory indications to it’s administration. The study included forty-one patients with confirmed RRP. Their examination included histological examination of papillomas, detection of HPV DNA in papilloma tissues using PCR technique, phenotyping of circulating lymphocytes (CD3+, CD4+, CD8+, CD25+, HLA-DR+) by means of flow cytometry. The levels of IFNγ, TNFα, GM-CSF, IL-2, IL-4, IL-5, IL-10, IL-12, IL-13 in laryngeal secretions were quantified by a multiplex immunoassay. In all cases, we revealed an initially decreased functional activity of Т-lymphocytes, as well as low contents of Т-killer and NK-cells. In laryngeal secretions, increased values of Th1-type-specific cytokines (IFNγ and TNFα) were found. Besides that, high levels of local IL-4 were detected thus being typical to alternative Th2-type response. Single inhalations 1000 000 ME of «Interal» or «Roferon» preparations were administered daily (a total of 10-15 millions ME per therapeutic course). Thirteen patients received the treatment after surgery, as an adjuvant therapy, and eleven patients underwent monotherapy. Complete tumor regression of tumors following this monotherapy was observed in 45,5% of the patients, whereas partial regression was registered in 45%. The effect was mostly expressed in frequently recurring juvenile papillomatosis with aggressive course and histological pattern of actively proliferating papilloma. In the patients with complete tumor regression, high initial levels of TNFα and IL-4/IFNг ratios were revealed initially in laryngeal secretions. When rIFNб was administered, an increase in Th1-type cytokines (IFNγ, IL-12, IL-2) and GM-CSF were revealed, as well as decrease of initially high levels of IL-10, like as lowered levels of IL-4 and IL-13. In cases of partial tumor regression, the levels of IFNα, IL-12, IL-2 and GM-CSF were decreased against initial values, and in the course of treatment they fluctuated within normal reference values. Cancellation of the therapy was followed by increase in IL-4 and IL-13 levels. Hence, the local rIFNα therapy is effective in controlling aggressive recurrent respiratory papillomatosis. Initial increase in TNFα and IL-4/IFNγ ratios in laryngeal secretions may be considered as favorable predictor of anticipated therapy, whereas increased levels of IFNα, IL-2 and IL-12 together with decrease (normalization) of IL-4/IFNγ ratio may reflect the efficiency of the treatment performed.

Abstract. Forty four patients with persistent allergic rhinitis and sensitization to the house dust mites were observed. All the patients have been examined in conformity with international diagnostic standards. The first group of observation included fifteen patients who received intranasal therapy by flutikasone propionate nasal spray at a dose of 200 mkg once a day for two weeks. The second group of observation included fourteen patients who received 10 inhalations of Affinoleukin® (a lyophilized complex of low molecular weight proteins from human leukocyte membranes with glycine), as aerosol, at a single dose of 2 units. Fifteen non-treated patients comprised a group of comparison. Eosinophil counts and concentrations of free hemoglobin (by immunometrical method in co-agglutination reaction) were made in nasal secretions twice (before treatment and two weeks later). It was found that the increase of free hemoglobin levels, as well as increase in eosinophil count in nasal secretions represents a symptom typical of exacerbation in persistent allergic rhinitis and reflects severity of disease. The therapy led to significant clinical improvement, decrease in free hemoglobin levels and eosinophil counts in nasal secretions, corresponding to clinical effect of both therapeutic modes of topical pharmacotherapy, resp., in 73% and 79% of the patients with persisting allergic rhinitis. Decrease in free hemoglobin level has allowed for the first time to reveal the immunotherapeutic efficiency of treatment with Affinoleukin® aerosol during exacerbations of persisting allergic rhinitis.

Abstract.The aim of present study was complex evaluation and analysis of hormone and immune profiles in the patients with subclinical and manifesting thyroid hypofunction, taking into account a therapeutic drug monitoring for optimization of levothyroxine treatment. Forty patients with thyroid hypofunction are included into the study: I group, patients with subclinical hypothyreosis (n=19) and the levels of thyroxine-binding globuline exceeding 700 nmol/l, who received levothyroxine at 50 μg daily after withdrawal of drugs for 10 days; II group, the patients with manifesting hypothyreosis (n=21), who received levothyroxine at 100 μg daily. A significant regress of clinical signs of hypothyreosis was registered in both groups following 3 months of receiving levothyroxine, employing an optimized mode of dosage. An immune/endocrine component is shown for the mechanism of levothyroxine action, which promotes the development of maximal hormonal effect, with respect to improvement of life quality in the patients with hypothyreosis upon optimization of therapy based on the therapeutic drug monitoring using liquid chromatography/mass-spectrometry.

Abstract. The objective of this study was to determine efficacy and safety of melatonin administered in addition to conventional atopic dermatitis treatment. Study design: open randomized parallel group study. Patients and treatment: Forty-six patients with exacerbation of moderate-to-severe atopic dermatitis were included into the study. The patients were randomized, to receive either complex conventional treatment, or conventional treatment plus melatonin at a daily dose of 3 mg, being administered at 9 P.M. Primary endpoint of the study: Severity scoring using SCORAD index. Assessment of pharmacological effects included counting functional evaluation of T-cells, B-cells and phagocytes, as well as morning and evening serum levels of IgE, IL-4 and IFN-γ. Results. In melatonin group, a statistically significant SCORAD index reduction was revealed, as compared with conventionally treated group (84% vs 60%). Addition of melatonin to conventional treatment caused a 63 per cent decrease in relative risks of unfavorable outcome, defined as absence of 20 per cent improvement by the SCORAD scale. Clinical improvement in melatonin group was associated with increase in CD8+cell counts, IgM levels and indices of Fc-dependent monocyte and neutrophil phagocytosis. Circulating IgE and IL-4 levels did significantly decrease. In melatonin group, there were significant differences between the morning and evening counts of CD3+, CD4+, CD8+, CD16+ cells, like as levels of circulating IFN-γ. These preliminary data suggest efficacy of melatonin administration in the patients with atopic dermatitis. Further research is needed to confirm these results.

Abstract. The main objective of this work was to identify allelic variants of cytokine genes at the polymorphic positions of G-308A TNFА, T-330G IL-2, С-590Т IL-4, С-703Т IL-5, and C-592A IL-10, and to assess their contribution to predisposition and resistance of human patients to progression of viral hepatitis C infection. We observed significant increase in frequency of T/G T-330G IL-2 genotype in HCV-infected patients, as compared to healthy individuals. Distribution analysis of C-590T promoter alleles of the IL-4 gene displayed a wide overrepresentation of C/T genotype among HCV-infected patients. Likewise, we have shown the G/A genotype of G-308A TNFA to be highly frequent in the group of HCV-infected patients, whereas this genotype was rare in the sample of healthy persons. When analysing allelic frequencies of cytokine genes at these polymorphic positions, we get an opportunity to predict predisposal for the chronic variant of viral hepatitis C in HCV-infected persons.

Abstract. The article presents the results of intraperitoneal administration of recombinant rat interferon-α to twenty Wistar rats with experimentally induced endometriosis. The following criteria of treatment efficiency were applied: presence of ectopic endometrium in transplanted segments of cornu uteri, proliferative activity of endometrioid cells, features of vascularization and leucocyte infiltration within endometrial foci. It was shown that local application of interferon-α caused regression of endometrioid epithelial heterotopias in 50 per cent of the cases. If endometrioid epithelium was retained, its proliferative activity did significantly drop under interferon-α application. In all transplants derived from rats treated with interferon-α, the degree of vascularization is reduced, accompanied by increased leucocytic infiltration (due to lymphocytes), along with decreased contents of macrophages within leucocytic infiltrates.

Abstract. A decrease in relative contents of CD50+-mononuclear cells and elevated serum levels of soluble CD50 antigen have been revealed in blood of the burn patients with different areas of skin lesions. The changes observed may influence the development of immunodeficiency which arises as a result of the burn trauma.

Abstract. The purpose of our study was to investigate whether S27P and -15С→T single nucleotide polymorphisms of the IL3 gene are associated with susceptibility to bronchial asthma (BA) in Russians living in the Central-Chernozem region of Russia. DNA samples obtained from 216 unrelated patients with BA and 214 healthy controls were typed for S27P and -15С→T polymorphisms in the IL3 gene by PCR-RFLP methods. Gender-based differences in the distribution of IL3 genotypes have been revealed between controls and patients with asthma. Both S27P and -15С→T polymorphisms were found to associate with common susceptibility to BA predominantly in females (p=0,05). Studied genetic variants of IL3 gene were in strong linkage disequilibrium with each other (p<0,0001). Further studies are required to investigate phenotypic expression of S27P and -15С→T polymorphisms of IL3 gene and to clarify their roles in the pathogenesis of bronchial asthma.

Abstract. An interleukin 4 polymorphism has been studied in Teleutians, Shorians, and Caucasoids living in the Kemerovo Region. The groups of Teleutians and Caucasoids are characterised with even or close-to-even distribution of the IL-4 alleles. The most widespread genotype in populations of Teleutians and Caucasoids was the 2R/3R heterozygosity, and 3R/3R proved to be the mostly rare. These data are indicative for mixing processes among Teleutians in the Kemerovo Region and Siberian Caucasoids. The major IL-4 genotype in Shorian population was 3R/3R, and the heterozygotic genotype 2R/3R took the second position.

Abstract. Fifty-three virtually healthy volunteers living in Chelyabinsk Region have been studied, with respect to contents of lymphocyte subpopulations, immunoglobulin concentrations, and the state of neutrophylic granulocytes. The inhabitants of Chelyabinsk Region exhibited decreased contents of CD3+ and CD4+ lymphocytes, along with increased levels of CD95+ cells, as compared with data from other studies. Neutrophilic leukocytes display decreased phagocytic activities and higher ability to produce active oxygen species. Regional standards are proposed for the immunological parameters.

Abstract. The data from literature and own results of the authors are presented in the article, concerning interactions between lymphocytes and platelets. It was demonstrated that the adherence of blood platelets to lymphocytes seems to be a reliable and highly informative test, which provides data on the state of immunity and haemostatic system. Sufficient section of this article deals with a role of adhesion molecules and cytokines in regulation of the lymphocyte-to-platelet adherence.

Recent works are presented about implementation of anti-adhesive molecules into treatment of various diseases that are accompanied by development of thromboembolic diseases.