Macrophages are among the most abundant cells of the respiratory tract, being characterized by their ability to have different phenotypes, depending on signals from the microenvironment (classically activated M1, alternatively activated M2). Despite contradictory literature data describing role of various macrophage phenotypes, they appear to be coupled to the systems protecting the organism from infectious pathogens and preventing development of excessive tissue responses. Phenotypical changes of lung macrophages are found in various respiratory diseases including bronchial asthma, chronic obstructive pulmonary disease, pulmonary fibrosis and infectious conditions. In this review article, we focused on the biology, origin and characterization of different macrophage phenotypes, and presented current data highlighting their role in development of chronic lung diseases, i.e., bronchial asthma, chronic obstructive pulmonary disease and acute infectious diseases.

Development and chronicity of inflammatory process in gastric mucosa may contribute to persistence of a number of microorganisms – Helicobacter (H.) pylori, Staphylococcus (S.) aureus, Candida species (spp.), Herpesvirus and others in the host organism. Many authors have recognized an important role of T helper (Th) type 1 and regulatory T cells in evolvement of gastritis, whereas importance of cytotoxic T lymphocytes (CTLs) is still to be confirmed. This review presents analysis of available scientific data about induction mechanisms of cellular cytotoxicity in inflammatory process affecting gastric mucosa. Bacterial populations, depending on their density, are able to regulate expression of genes encoding synthesis of protein virulence factors, thus accelerating adaptation for changing environmental conditions. Upon receptor-mediated recognition of characteristic microbial structures, i.e., pathogen-associated molecular patterns (PAMPs) and danger signals altered by stress, or cellular structures damaged by infectious pathogens (DAMPs), transcription factors are activated, thus leading to production of early pro-inflammatory interleukins (IL), interferons (IFN) type I and induction of immune responses. It is shown that the antigens of H. pylori and Candida spp. promote infiltration of mucosa gastric by activated CD8+CTLs, and Herpesvirus induce a significant increase in the number of perforin-positive (Pr+) CD8+ and CD16+ cells, phenotypic changes in CD4+lymphocytes, with acquisition of direct cytolytic activity.

The main function of thymus, a central organ of lymphoid system, is to form a pool of immunocompetent autotolerant thymocytes. The process of lymphocyte differentiation within thymus largely depends on organization level of the vertebral animal and its environment (habitat). So far, variability of morphological parameters of lymphoid component in thymus have been poorly studied for distinct representatives of various terrestrial vertebrate, due to the lack of comparative morphological studies. Therefore, the main purpose of our work was to identify this kind of dependences. In this study, on the example of prepubertal representatives belonging to four classes of vertebrate animals (Chordata, Vertebrata) including humans, we conducted a comparative morphological study of variability for main micromorphological parameters of lymphoid components in thymus gland. We have studied 212 preparations of thymus glands from 4 classes of vertebrate animals: Amphibia, Reptilia, Aves, Mammalia. The changes in total amount of thymocytes were studied for cortical and medullary substance of thymus gland. Percentage of thymocytes at different maturity stages, and mitotic thymocyte indexes were also studied.
On the basis of these data, a conclusion was made about differences in intensity of processes, connected with maturation and proliferation of lymphoid cells in thymus gland of distinct animals which are different in organization level and habitat could be determined by with different influence of adaptive changes which occurred in the course of evolution of vertebrates during. It was found that the morphological parameters reflecting the characteristics of the differentiation processes and maturation of lymphocytes in thymus are largely determined by adaptive changes that arose in the vertebrate evolution during the formation of true terrestrial and warm-bloodedness. Comparison of amphibians and reptiles, as well as cold-blooded beings with warm-blooded animals revealed differences in the number of thymocytes at different maturity levels in cortical and medullary zones, as well as differences in thymocyte division rates. In turn, comparison of mitotic index for the thymocytes of all vertebrates, within this morphological range, showed that intensity of thymocyte proliferation primarily depends on the energy capacity of the given organism. However, specific adaptations associated with evolution to a distinct certain living form (for example, adaptation of birds to flight) also exerts a significant effect upon rates of thymocyte division. Morphological features characteristic to the human thymus were determined, and possible causes of such differences were identified. It was found, that morphological parameters of the lymphoid component in human thymus are more similar to those of thymus from cold-blooded vertebrates which is already evident from early stages of ontogeny. We guess that this finding may be explained by exposure of humans to numerous unfavorable anthropogenic factors, which lead to some deviation of thymic morphology from the values, which are observed in mammals from the natural habitat. The obtained data are of interest for theoretical and practical biology and medicine.

In vitro differentiation of donor blood monocytes to macrophages (Mph) following GM-CSF treatment was accompanied by a significant increase in the levels of gene transcription signaling receptors TLR7 or RIG1. The levels of intracellular viral RNA (M1 gene) in Mph remained high upon infection by influenza virus A H1N1pdm (Moscow 2009) for 24-96 hours. The innate immunity reactions caused by influenza virus show individual features: they are decreased in Mph from donor 1 which had initially high level of endosomal TLR7 gene activity, and it increased by influenza virus in MPh from donor 2 who had a very low level of TLR7 gene expression. The influenza H1N1pdm virus weakly stimulated expression of gene RIG1 and production of inflammatory cytokines in Mf in donor 1. The differences may be connected with individual sensitivity of the donors to influenza infection.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease of nasal cavity and paranasal sinuses characterized by inflammatory infiltration of nasal mucosa followed by damage to collagen framework, leading to tissue remodeling and polyp formation. Its pathogenetic mechanisms still remain obscure. To study appropriate trends, an evaluation of cellular immunity indices was carried out in twenty patients with the CRSwNP. Bilateral CRSwNP was clinically confirmed by endoscopic examination of nasal cavity and computed tomography scan of paranasal sinuses. In order to define the clinical phenotype of CRSwNP, allergy skin testing and a specific questioning were performed. As based on results of this study, the patients with CRSwNP were divided into following subgroups: CRSwNP + Asthma; CRSwNP + intolerance to non-steroid anti-inflammatory drugs (NSAIDs); CRSwNP + atopy. Common subpopulations of lymphocytes, such as CD3+, CD4+, CD8+, CD16+, CD19+, CD25+, CD27+, CD45+, CD45R0+, CD45RA+, CD56+ and CD127+ were detected in peripheral blood using flow cytometry techniques. Immunological data from 356 apparently healthy individuals were used as reference parameters for the control group.
The study has revealed an increase in T regulatory (Treg) cells (CD4+CD25brightCD127lowtoneg), elevated absolute or relative amounts of NK cell numbers (CD3-CD16+CD56+) in parallel to sharply increased numbers of activated NKs (CD8+CD3-) in 100% of the patients, and higher absolute contents of memory B-cells (CD19+CD5-CD27+) in CRSwNP patients. When performing comparative analysis of immunological
characteristics in peripheral blood between different subgroups (CRSwNP + Asthma; CRSwNP + intolerance to NSAIDs; CRSwNP+ atopy), and patients with uncomplicated CRSwNP (who didn’t have such pathology), we have proven significantly increased numbers of NKT lymphocytes (0.22±0.04), and decreased T lymphocyte activation index, i.e., a ratio of activated T helpers to memory T cells (CD4+CD45R0+) (24.4±1.72) among CRSwNP patients complicated by intolerance to NSAIDs. When comparing immunological characteristics of the patients with concomitant bronchial asthma to other subgroups, which have CRSwNP, or the patients with/without atopy, we have not detected any statistical differences for immune indexes studied (except elevation of blood eosinophils).

Uterine fibroids take a second place in the structure of gynecological diseases, after inflammation of genital organs, with a share of 40%. The aim of the study was to investigate cytokine profile and factors of immune dysfunction in patients with uterine fibroids complicated by hemorrhagic syndrome during a course of hormone replacement therapy.
А detailed comparative analysis of a survey was performed in 95 women with uterine fibroids. Tumor size did not exceed 12 weeks of pregnancy, mainly with intramural and subserous localization of nodes, having indications for conservative treatment. The main group consisted of 43 patients with uterine fibroids and clinical signs of hemorrhagic syndrome observed in the course of hormone replacement therapy (Buserelindepot 3.75 mg). In a comparison group (n = 52), treatment of fibroids with hormonal therapy was not carried out.
A control group comprised healthy women (n = 27). The survey consisted of a comprehensive ultrasound scan with Doppler ultrasound apparatus HITACHI 5500. The immune parameters were evaluated as contents of cytokines (interleukins IL-1β, IL-4, IL-6, IL-2, IFNγ, TNFα) and levels of the Fas-ligand apoptosis marker in blood serum using solid-phase immunoassay technique. For identification of urogenital infection pathogens, methods of diagnostic PCR and ELISA were used.
The results of the study were as follows: it is established that emergence of hemorrhagic syndrome on the during hormone therapy for uterine fibroids is associated with activation of latent forms of urogenital infections, being a probable result of potentiating immunosuppressive action of hormonal drugs that promote alterations of immune status, reduction of Th1 and Th2 lymphocyte functions, as well as significant inhibition of apoptosis. In the main group, IL-1β, IL-2, IL-4, IL-6 and IFNγ concentrations were decreased by 1.3 to 1.5 – fold, whereas TNFα and FasL contents were 2 times lower than the levels in control group. In addition, qualitative analysis of uterine hemodynamics has shown that the complications associated with hormone therapy of uterine fibroids are accompanied by a significant increase of the systolic blood flow velocity in the uterine arteries (1.8%), against decrease in diastolic blood flow (2.5 times) and increased resistance index of the vascular wall (1.6 times), as compared with appropriate parameters in healthy women. In conclusion, the received data suggest a need for more detailed examination of women, in order to detect chronic forms of urogenital infections, by means of improving conservative treatment strategies of uterine fibroids, reducing frequency of complications and effectiveness of hormone therapy

At the present time, arterial hypertension is the most common somatic pathology among young and able-bodied persons. Development and progression of hypertension in young people occupied with stressful jobs presents a particular problem. Anxiety and depression arise quite commonly in such persons subjected to chronic stress. Direct pathophysiological effects of anxiety and depressive disorders upon cardiovascular system leads to development of disturbances of basic regulatory processes and life-threatening clinical forms of ischemic heart disease and hypertension. However, despite sufficient data about the impact of anxiety and depressive disorders on the course of cardiac pathology, some open questions remain concerning the degree of changes in neuropeptide-cytokine pool of immune system in young, intensively working hypertensive patients.
Moreover, there is lack of knowledge concerning interdependence in functioning of the major regulatory systems (autonomic nervous and immune) in such patients.
In this connection, the aim of this work was to study cytokines of the immune system, and the levels of betaendorphin production in hypertension, proceeding with astheno-neurotic disorders in young men of intensive specialties, as well as study of interactions between the indices of autonomic nervous system functioning, and immunity parameters in these patients. The following groups were under study: 1st (n = 34) included patients with hypertension and astheno-neurotic problems; 2nd (n = 20), patients with hypertension without psychological disorders, with acute or chronic stress in previous history (controls). Neuropeptide-cytokine profile of the immune system was evaluated by levels of proinflammatory cytokines (TNFα, IL-1β, IL-6), antiinflammatory cytokines (IL-4, IL-10), and β-endorphin.
In the course of clinical and laboratory examination, we have found that, in the patients with hypertension and astheno-neurotic disorders, activation of proinflammatory cytokines (TNFα, IL-1β, IL-6), suppression of anti-inflammatory cytokines (IL-4, IL-10), and reduced β-endorphin in the blood are registered. Moreover, the disturbances detected showed the mutual interactions between autonomic nervous and immune systems in these patients.

So far, there is no clear understanding for the reasons causing tuberculosis generalization in children. Development of generalized infection could be also determined by some features of immune response which may depend on genetic markers. The aim of our work was to study the features of HLA-DRB1 and HLADQB1 allele distribution in children with generalized tuberculosis (gTBC). Materials and methods: we have observed 40 children at the age of 1 to 15 years suffering from gTBC. After performing a standard phthysiatric examination, including molecular-genetic diagnostics of surgical material, multispiral CT, immunological testing, as well as HLA-DRB1 and DQB1 alleles. We have studied distribution of the HLA-DRB1 and DQB1 alleles comparing it with a group of healthy donors (n = 100).
The results did not show significant differences in HLA-DQB1 allele distribution between the gTBC patients and comparison group. Meanwhile, when comparing genotypes for HLA-DRB1 loci, we have revealed a significantly lower prevalence of the *01 allele of HLA-DRB1 (12.5% versus 31.0%; χ2 = 4.08; р < 0.05), which could be considered a predisposing factor, as well as a higher incidence of *14 allele (7.5% against 1.0%; χ2 = 3.67, р < 0.05) of HLA-DRB1 gene, thus suggesting its protective role.
Conclusions: we did not find any significant differences for HLA-DQB1 distribution between pediatric patients with generalized tuberculosis and healthy donors, whereas * 01 allele of HLA-DRB1 may predispose for gTBC, and the *14 allele could be protective in evolving generalized tuberculosis in children.

HLA-G is the main molecule through which provides tolerance of maternal immune microenvironment to the semi-allogeneic embryo. Polymorphic variant of 14-bp ins/del in the HLA-G 3’UTR gene affects stability and expression of specific mRNA and, thereby, efficiency of immune rejection blockade of the semi-allogeneic embryo. Immune interactions in the “mother – fetus”system can cause teratogenic effects. Congenital heart defects are the dominant pathology among congenital malformations of the fetus and newborns. The aim of the study was to search possible associations between polymorphic 14-bp ins/del variants of maternal HLA-G 3’UTR gene, and reproductive losses or congenital heart defects in their children. Subjects and Methods. We have examined 103 women who had children with congenital heart defects, 21 women with reproductive losses at up to 9 weeks of pregnancy, 101 women with two or more healthy children. Results. It was revealed that the minor homozygous genotype HLA-G 3’UTR 14-bp ins/14-bp ins (OR = 5.25; 95% CI = 1.31-21.11), and allele HLA-G 3’UTR 14-bp ins (OR = 2.34; 95% CI = 1.13-4.84) were markers of early reproductive loss in women. Polymorphic variant of the 14-bp ins/14-bp del gene variant of HLA-G 3’UTR in the mothers was not significantly associated with birth of infants with congenital heart defects.

Catalytic properties of immunoglobulins are widely studied within recent years. It was found that nuclease activity of immunoglobulins is increased in systemic autoimmune diseases. Given some pathogenetic features of rheumatoid arthritis and reactive arthritis, it is appropriate to clarify the nature of nuclease activity in these diseases. Determination of DNAse activity of immunoglobulins with different DNA substrates, and search for specific substrates for distinct clinical entities could serve these purposes. The aim of present work is to determine DNase activity of the polyclonal class G immunoglobulins in rheumatoid and reactive arthritis using various methods.
Different methods are used to evaluate nuclease activity. In this paper we present newly developed and modified techniques for determination of DNAse activity of polyclonal IgGs. Particular attention was paid to the electrophoretic method of DNase activity assessment. Polyclonal IgG isolated from blood serum of patients with rheumatoid arthritis and reactive arthritis were used for assays. In this study, we demonstrated the presence of an inhomogeneous DNase activity of immunoglobulins in relation to different substrates.
Along with calf thymus DNA, we used bacterial plasmid DNA and PCR products based on bacterial gene sequences. Levels of DNase activity by rivanol clot method with calf thymus DNA as substrate proved to be higher in patients with rheumatoid arthritis than the control values (p < 0.01). DNase abzyme activity in patients with rheumatoid arthritis was elevated, as compared to the patients with reactive arthritis (p < 0.01).
When examining ability of the IgG to hydrolyze procaryotic DNA (bacterial plasmid DNA and PCR products, based on bacterial genes), we obtained heterogeneous results. Different Ig samples showed varying degrees of DNA hydrolysis. Abzyme hydrolysis of DNA substrates longer than 700 bp was more pronounced, as compared to short DNA substrates (100 base pairs).
Conclusions: 1) antibodies having deoxyribonucleic activity are present in serum of patients with rheumatoid arthritis, reactive arthritis; 2)DNase abzymes exhibit heterogeneous ability to hydrolyze various DNA substrates; 3) Abzyme-medicted hydrolysis of DNA substrates longer than 700 base pairs is more pronounced, as compared to a short DNA substrates (100 bp) length.

The paper presents results of clinical application of autologous stromal-vascular fraction (SVF) cells in patients with degenerative osteoarthritis (OA) of the knee, grade II and III (Kellgren–Lawrence scale).
We recruited six patients with knee OA (3 men and 3 women; median age 64 years) with mean disease duration of 7 years. All the patients were administered a single intra-articular injection of autologous nucleated SVF cells at an average dose of 16.8±0.9 × 106 per joint (a total of 11 joints). The patients did not experience any serious side effects (allergic, toxic or inflammatory) related to the knee injection. Patient surveys at 1 month after SVF administration revealed a decrease in the severity of pain, as measured by a visual analog scale (VAS) and a specialized 100-point scale KOOS (subscale "pain") (p < 0.05 on both scales). Moreover, the patients reported improvement in the joint functions and quality of life related to affected joints on a KOOS scale (p < 0.05). These positive clinical changes persisted during 6 month follow up. Significant improvements were noted in ultrasound findings, with increased thickness of the cartilage layer at 3 months (in 73% of cases) and at 6 months (in 82%). Our pilot study demonstrated the safety and tolerability of intra-articular injection of autologous SVF cells in patients with moderate to severe OA. The results obtained also indicate a significant antiinflammatory effect of autologous adipose tissue SVF cells, which is manifested at the early stages of cell therapy. Our further investigations will be focused on exploring the SVF stimulatory effects on regeneration of damaged joints.

Laboratory parameters of IgE-mediated immunological reaction (total IgE) were studied. Subjects with impaired carbohydrate metabolism and persons with diabetes mellitus were classified for blood groups 0(I), A(II), B(III) (n = 93). We determined total IgE, glucose levels and percentage of glycosylated hemoglobin (HbA1c) in blood serum; as well ABO blood groups. Comparison of these parameters in patient cohorts with 0(I) and A(II), B(III) blood groups showed different reactogenicity, depending on the degree of carbohydrate metabolism disturbance and ABO group specificity of antigenic determinants of blood glycoproteins. There was a strong direct correlation (r = 0.8) between blood group 0(I) antigens, and incidence of type 2 diabetes mellitus (DM). The highest correlation degree was observed between the blood group A(II) and type 1 diabetes onset of (r = 1.0). The smallest percentage of DM and the smallest correlation (r = 0.67) were observed in patients, B(III) blood group is located. In cases of sufficiently altered carbohydrate metabolism, the blood group 0(I) and A(II) carriers had total IgE of 43.61±15.12 kIU/L, and 86.2±42.61 kIU/L, respectively, thus being, on average, 4-times lower than in B(III) blood group in whom total IgE in type 2 diabetes was 2-fold higher than normal values, being 209.65±52.5 kIU/L.

Increase prevalence of bronchial asthma (BA) is noted recently. That’s why its treatment remains an urgent problem in allergology. Along with congenital atopy, a significant role in formation and development of a disease is given to hyperreactivity of bronchial tubes which is connected with a alterations of their epithelial membranes. However, sampling of bronchial epithelium cells is carried out by means of bronchoscopy with a biopsy which is an invasive procedure. Therefore, bronchial hyperreactivity is a relative contraindication for this intervention. Meanwhile, there exists a non-invasive method of integrated cellular membrane assessment.
Analysis of membrane transformation in erythrocytes which do not have their own metabolism may be an informative model of cellular membranes in the organism in general. We have examined 52 persons (2 to 17 years old) including 20 children with bronchial asthma and the comparison group comprising 32 healthy ageand sex-matched children. Percentage of spontaneous red blood cells (RBC) transformation in the patients was carried out by means of light microscopy in whole blood smears made of native cell suspension. Children with bronchial asthma (2.6%) exhibited more frequent occurrence of destructive RBC forms than in healthy children (0.8%, р < 0.05), with predominance of stomatocytes (0.55% and 0,1%) which were >5-fold more common in children with bronchial asthma (р < 0.05). Respectively, transitional forms were significantly more often encountered in control group (39.9% against 34.12%), р < 0.05. Bronchial asthma is characterized by stomatocytic way of RBC transformation.
An indicator of compensatory transformation (a ratio of transitional-to-destructive RBC forms) seems to represent an integrative criterion for membrane ability of reversal to normal state. Children suffering from bronchial asthma (р < 0.05) have decreased levels of this compensatory transformation indicator as compared to healthy children (2.1 and 3.5 respectively), as shown in our study. Evaluation of external respiratory function is chosen as the objective parameter defining severity of bronchial asthma.
A strong reverse correlation (R = -0.82) is shown between FEV1 index and quantity of spheroids (transitional forms), as well as significant direct correlation (R = 0.76) between FEV1 and indicator of compensatory transformation level. Hence, we noted that the patients with bronchial asthma have disturbances of erythrocyte transformation, when compared to healthy children. There is a direct dependence between severity of a disease and expressed changes of RBC membrane transformation.

Most authors ascribe pathogenesis of parodontitis to alterations of oral microbiota and mechanisms of local immunity. One may therefore assume that of the concepts of pathogenesis, diagnosis and treatment of the disease may be successfully developed when implementing immunological studies of oral fluid. The aim of present study was to characterize cytokine status of the oral fluid in patients with chronic periodontitis. The study included 101 subjects who were divided into two groups, according to results of retrospective analysis, i.e., study group (69 patients) with moderate or severe periodontitis, and control group (32 virtually healthy volunteers).
In control group of patients, cytokine levels corresponded to normal values. In the patients with periodontitis, we have revealed increased IL-2, IL-4 levels. This finding suggests that the cytokine balance in periodontitis is characterized by predominance of Th2 produced factors, i.e., activation of “anti-inflammatory” immunemediated mechanisms. We have also determined VEGF levels in oral fluid, since disturbances of microcirculatory bed seem to be important in evolving periodontitis, along with immune shifts. The VEGF content in oral fluid also tended to increase in the patients. We have found that the IL-4 level in the oral fluid is of high diagnostic value in periodontitis, with diagnostic sensitivity of 88%, and diagnostic specificity of 99% (AUC = 0.95).
In our study, we have obtained data corresponding to general view on altered local immune mechanisms in developing chronic periodontitis. This shift manifests as imbalance in cytokine production, especially, by activated IL-4 production. One may assume that this cytokine exerts both pathogenetic effect (immunomediated destruction of tissues) and protective action (stimulation of antimicrobial immunity) in periodontitis.
Prevalence and ratio of these effects seems to determine progression rates and development of complications in the disease. Determination of IL-4 content in oral fluid can be considered a potential quantitative tool for laboratory diagnosis of periodontal tissue diseases, being a marker of activity in this pathological process.