Evolution of existing paradigms on regenerative capacity of the central nervous system (CNS) and eventual role of immune cells in restoration of damaged nervous tissue offers new prospectives in treatment of neurological disorders based on immunotherapeutic approaches. Present review article addresses a role of macrophages in restoration of damaged CNS and provides data on functional heterogeneity of resident tissue macrophages (microglia), and monocyte-derived macrophages. We discuss possible ways of monocyte recruitment to CNS, relationships between microglia and recruited macrophages, as well as M1/M2 balance in neurological conditions. Moreover, the review proposes an experimental rationale for macrophage engagement into the CNS damage reconstruction, and concerns the mechanisms of macrophage regenerative activity. In summary, the data presented here allow us to suggest macrophages as a novel therapeutic target for suppression of neuroinflammation and enhancement of reparative processes. The first steps in the field are encouraging, with respect to clinical application of monocytes/macrophages or M1→M2 switching technologies for treatment of the neurological disorders, thus presuming a need for further research in this direction.

Natural killer (NK) cells represent a lymphocyte subpopulation which is capable of contact cytolysis of virus-infected cells and tumor cells, being a source of cytokines which stimulate other immune cells and promote immune response. NK cell differentiation is connected with a consequent acquisition of specific NK cell receptors by stem cells and formation of functional characteristics inherent to natural killer cells. The aim of this review was to describe the CD56dim and CD56bright populations of NK cells in the course of their differentiation. The authors describe NK surface receptors and expression of transcription factors at various steps of the NK differentiation. We present comparative characteristics of data concerning cytokines and cellular microenvironment influence upon NK cell differentiation, and examine a phenomenon of existing memory-like NK cells. Uterine NK cell differentiation is of special interest, since these cells represent a special NK cell population which prevails among decidual lymphocytes during pregnancy and participates in the process of placental formation and development. This review considers some features of uterine NK cell differentiation, taking into account a possibility of formation of this NK cell population from both peripheral blood NK pool, and in situ proliferation. Moreover, functional studies of the uterine NK cells allow to get closer to understanding the role of NK cells during pregnancy and abnormality of utero-placental bed regulation by NK cells in cases of pregnancy failure.

The levels of TLR/RLR gene expression and production of some cytokines were studied in monocytic THP-1 cell line during its differentiation to mature macrophage-like forms induced by phorbol 12-myristate 13-acetate (PMA) treatment for 1 and 5 days in vitro. For the first time, we have shown high induction levels for the genes that encode signaling immune receptors and transcription factors in response to PMA, as well as inhibitory effects of TLR3, TLR7/TLR8, TLR9-agonists in mature macrophages. The PMAactivated THP-1 macrophage-like cells secreted large quantitities of inflammatory IL-1β and TNFα cytokines into culture medium.

Imbalance of the proteolysis/antiproteolysis system is known to be among key components of immunofibrogenesis of liver in cases of chronic hepatitis C. To evaluate these aspects, we studied several factors of liver tissue remodeling in blood serum and local samples from HCV patients associated with liver fibrosis. We determined the levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), MMP-9/TIMP-1 and MMP-9/TIMP-2 complexes. Clinical, laboratory and instrumental examinations have been made for 81 patients with chronic hepatitis C who did not receive antiviral therapy, and 22 healthy volunteers. Extracellular matrix protein (ECM) profile was studied in 103 serum blood samples and 32 liver supernates using ELISA technique. Statistically significant increase of MMP-9 contents (p < 0.05) and its complexes with TIMP-1 (p < 0.05) and TIMP-2 (p < 0.01), as well as low levels of type 1 inhibitor (p < 0.05) were revealed in blood serum of HCV-infected patients, as compared with control group. Protein assays in liver supernates of hepatitis C patients reflecting extracellular matrix state revealed an eight-fold increase in MMP-9/ TIMP-1 complex, as compared with control group (p < 0.05). The values of other proteolytic/antiproteolytic factors proved to be low (p < 0.05). An imbalance in protease contents in blood serum and liver biopsies was revealed, showing differently directed changes. I.e., serum values of MMP-9, TIMP-1 and MMP-9/TIMP-2 during transition of liver fibrosis to cirrhosis (F0 to F4) became decreased (p < 0.05), associated with increased liver concentrations of these proteolytic enzymes (p < 0.05). In summary, we conclude that the data obtained in our study suggest an imbalance of proteolysis/antiproteolysis system leads to a dysregulated liver tissue remodeling in patients with chronic hepatitis C.

The aim of this study was to evaluate some features of subpopulational profile and functional activity of monocytes in patients with acute pancreatitis. The study included 33 subjects with acute pancreatitis of middle-to-severe degree. Thirty-five healthy age-matched people served as a control group. The study of monocyte phenotype was performed by flow cytometry. Phagocytic ability of monocytes was determined by flow cytometry, by means of FITC-labeled staphylococcal protein A. We assessed percentage of fluorescent monocytes (defined as phagocytic index), like as average cell fluorescence (phagocytic number). The phagocytic indexes were determined for a total monocyte fraction, and well as for distinct cell subpopulations (CD14+CD16- , CD14dimCD16+ и CD14lowCD16+). Intensity of respiratory burst in the monocytes was evauated with chemiluminescence analysis. We used two indicators (lucigenin and luminol) to assess production of primary and secondary reactive oxygen species. In the patients with acute pancreatitis, we have found certain changes in blood monocyte subpopulations and their functional activity. The changes in monocyte subpopulations in acute pancreatitis were characterized by increased numbers of inflammatory cell forms in blood (CD14lowCD16+), along with while near-normal contents of the cells with «classic» (CD14+CD16- ) and «non-classical» phenotype (CD14dimCD16+), having been within reference ranges. It is assumed that high levels of pro-inflammatory monocytes may produce a pathogenetic «circuit» which is characterized by positive mutual stimulation of monocyte-mediated inflammation in local (pancreatic) and blood compartments. Apparent development of such mutual induction of inflammatory events may determine a low efficiency of anti-inflammatory therapy in acute pancreatitis. The functional characteristics of the monocytes in patients with acute pancreatitis are defined as a decrease in phagocytic activity and low respiratory burst intensity. Reduced phagocytic activity of monocytes was detectable in all the cellular subpopulations. Decreased intensity of monocytic respiratory burst in acute pancreatitis depends on low background and induced synthesis of both primary and secondary reactive oxygen species. Thus the patients with acute pancreatitis exhibit imbalanced with respect to synthesis of primary and secondary reactive oxygen species in the monocytes may result from specific action of circulating pancreatic enzymes upon the cells, or due to increased concentrations of pro-inflammatory cytokines. The imbalance between the monocyte subpopulations and reduction of their functional activity in acute pancreatitis may represent an immunopathogenetic basis for development of pancreatic necrosis and sepsis.

Studies of potential biomarkers in periodontology are focused on analysis of oral liquid which revealed a number of potential salivary periodontitis biomarkers. The biomarkers should be simple to perform, with easily interpretable results providing relevant information from initial stages of disease, to measure its activity, thus reflecting the disease evolution (e.g., from gingivitis to periodontitis). However there are some more scientific, clinical and technological tasks to develop successful clinical salivary diagnostics for periodontitis treatment. The purpose of our study was to assess interrelations of IFNγ and neopterine in oral fluid of the patients with chronic generalized periodontitis (CGP), aiming for more complete understanding of periodontal disorders and at patients with an intolerance of stomatologic materials. It is shown that the average levels of neopterine in exacerbated moderate-stage CGP patients was raised before treatment to 11.6 [8.0; 15.4] ng/ml, as compared with post-treatment level of 5,5 [4,1; 7,1] ng/ml (р < 0.05) Average amount of IFNγ in oral fluid from these patients group was 6.7 [5.0; 8.7] pg/ml before treatment, as compared to 5.5 [3.5; 7.1] pg/ml after treatment (no significant difference). Neopterine level in patients with exacerbated severe CGP before treatment was even higher than in patients of moderate/severe group, with an average of 8.2 [6.0; 9.9] ng/ml thus sufficiently exceeding post-treatment levels, i.e., 5.5 [4.1; 7.1] ng/ml (р < 0.05). A course of periodontal therapy in this group was associated with sufficient changes of IFNγ levels in oral fluid: appropriate levels before and after treatment were, respectively, 8.6 [7.3; 11.2] pg/ml, and 5.4 [4.3; 6.7] pg/ml. We have revealed that the OHI-S and SBI indexes characterizing conditions of oral cavity are interconnected with local neopterine and IFNγ levels. It is shown that an increased neopterine concentration in oral fluid and its correlation with SBI index in CGP patients is an independent biomarker of therapeutic effect. The patients with a CGP exhibited a highly significant correlation between initial levels of IFNγ and neopterine in oral fluid (R = 0.82; p = 0.0001), and after treatment (R = 0.78; p = 0.0001) in both groups of the patients.

Level of a neopterin and IFNγ at patients with complaints to intolerance of dentoprosthetic materials before removal of artificial limbs and after removal of orthopedic designs authentically didn't change.

A control group included seventeen conditionally healthy people (Group 1). Eighty-eight patients with proven bronchial asthma (BA) at the age of 22 to 48 were enrolled into the study. I.e., Group 2 included nine patients with well-controlled BA. Group 3 included persons with partially controlled BA (n=79). There were 8 people with easily treated BA in group 2, and 57 such cases in Group 3. The levels of interleukins (IL-4, IL-10, IL-17A), interferon-γ (IFNγ), and tumor-α necrosis factor (TNFα) were monitored by means of flow cytometry technique. The parameters of cellular immunity were registered by flow cytofluorimetry assays. Phagocytosis indicators were studied by means of D. Mayansky method, metabolic activity of neutrophils, by the B.Park method, as modified by E.Shmelev. Evaluation of cellular immunity did not reveal statistically significant differences for distinct CD subpopulations between healthy controls and BA patients. The patients with controlled and partially controlled BA exhibited some changes in cytokine concentrations, i.e., increased IL-4, IL-17А, IL-10 and TNFα levels; changes in phagocytosis and oxygen dependent bactericidal activities of neutrophils. We have revealed higher concentrations of IL-4, IL-17А in the less controlled BA (group 3) , as compared with group 2. TNFα induction remained at significantly higher level in both groups of BA patients, exceeding mean control values by 2.3 times. The degree of IL-10 production in group 2 with controlled BA was significantly higher than in group with partial disease control (group 3, p < 0.001), thus suggesting application of IL-10 levels as an index of active inflammation control. Patients with BA (groups 2, 3) exhibited a decrease of basal IFNγ, as compared to healthy people (p < 0.001). In group 3 (partial control), this parameter was 3-fold lower than in healthy persons. Evaluation of monocyte/phagocyte functions showed statistically significant differences between BA patients and healthy persons. Functional reserve of granulocyte activity and oxidative metabolism were decreased to a similar degree in the patients with well-controlled and partially resistant BA, thus showing their independence on the quality of disease control.

Concomitant infection is known to decrease non-specific immunity levels, thus negatively affecting clinical outcomes in tuberculosis patients. Development of specific immune response against most common pediatric infections, e.g., pneumococcal infection, is possible both in children with latent tuberculosis and in respiratory tuberculosis. The study contains data concerning results of immunization with Pneumo23 vaccine against pneumococcal infection in 35 children (3 to 14 years old) with different manifestations of MBT infection observed at the St. Petersburg Research Institute of Phthisiopulmonology. The vaccination efficiency was evaluated by incidence of acute respiratory infectionsm acute otitis media, and community pneumonias within one year before and after vaccination performed. Clinical safety of the vaccination was determined as the number of general and local reactions registered following vaccination.

Incidence of post-vaccinal reactions did not differ significantly between the clinical groups and did not exceed the values reported by the vaccine manufacturer. Post-vaccinal period was event-free in 94.3% of vaccinated children, without any negative effects upon the underlying tuberculosis process. In Group 2, all the children were complication-free over the post-vaccinal period. Both groups exhibited a statistically significant increase of IGg levels by the post-vaccination day 14…45. The PPV23 vaccination was not followed by postvaccinal complications, or worsening of tuberculosis infection. Hence, anti-pneumococcal vaccination is effective for prevention of acute respiratory infections, both in MBT-infected children and in patients with local tuberculosis affection.

Genome instability of transformed cells, being the most common factor of malignancy, may result into production of abnormal proteins in these cells. Normally, the newly formed proteins are recognized by immune system, thus causing elimination of the transformed cells. Nevertheless, the phenotypic instability promotes formation of specific transformed cells which suppress effector immune reactions and/or are unrecognizable by cytotoxic lymphocytes. NKG2D is one of the most important activating receptors expressed by NK cells. It serves as a major recognition receptor for detection and elimination of tumor and infected cells. The ligands for NKG2D include surface or circulating non-canonical MICA/B molecules from class I major histocompatibility complex (MHC class I chain–related proteins A and B). MICA and MICB are expressed scarcely, if at all, by the most normal cells, being, however, upregulated in cancer cells and virus-infected cells.

NKG2D receptor-ligand interaction is important for regulation of anti-tumor immune reactions. The soluble form of MICA accumulated in blood due to proteolytic shedding from tumor cell membranes is able to inhibit the NKG2D mediated anti-tumor cytotoxicyty and, therefore, promote the immune escape. The aim of our study was to estimate blocking effects of soluble recombinant human MICA protein (rhsMICA) upon NKG2D receptor of NK cells.

Mononuclear cells were isolated from peripheral blood, followed by incubation with of rhsMICA at different concentrations (0, 1, 5, or 10 µg/ml), staining with anti-CD314 (NKG2D) mAbs on the CD3- CD56+NK cells, and flow cytometry analysis. A similar treatment protocol was applied for IL2- and IL15-activated mononuclear cells isolated from the melanoma patients.

It has been shown that brief incubation of lymphocytes with rhsMICA caused a significantly reduced expression of NKG2D receptor on the surface of cytotoxic lymphocytes, both from healthy donors and melanoma patients. These changes depended on the MICA dose. Meanwhile, the cytokine-activated lymphocytes seem to become more resistant to inhibiting effects of rhsMICA, and, thus, do not cause any significant reduction of NKG2D expression on the activated NK cells. This fact may be a pre-requisite for usage of activated NK-cells for adoptive immunotherapy of cancer patients with MICA-positive malignancies.

At the present time, immunosuppressive role of extracellular adenosine in carcinogenesis is actively investigated. Colorectal cancer is one of the most common types of malignant neoplasms in Russia and worldwide, but the role of mediators of adenosine-dependent immunosuppression, such as CD39 (that hydrolyze ATP to adenosine), CD73, A2AR, is not yet clear in patients with colorectal cancer. The levels of specific mRNAs for A2AR, ectonucleotidase CD39, and CD73 genes were assayed in white blood cells of the patients with colorectal cancer. The results have shown that the CD39 mRNA content is increased in the patients with colorectal cancer in the course of the disease progression. Meanwhile, no significant difference for CD73 gene expression was found between the patients and healthy donors. Moreover, an increase in A2AR mRNA expression was noted for the patients with advanced colorectal cancer, thus presuming potential activation of adenosine-A2AR-mediated immunosuppressive mechanism. Furthermore, the CD39 expression on T cells was elevated in parallel to the cancer progression. The most significant changes in CD39 expression were observed for both T helper and Treg cell populations at the late stages of colorectal cancer. Similarly, a direct correlation was revealed between CD39 expression on CD4+CD25+CD127lo/-Treg cells, and changes of A2AR mRNA levels in leukocytes from the cancer patients.

The work represents a family which includes two siblings with chromosome 22q11.2 deletion syndrome. Their mother carries the same chromosome anomaly, but with apparently normal phenotype. Hence, this interesting case of 22q11.2 deletion syndrome exists in 2 generations of the same family. The aim of this study was analysis of phenotypic manifestations in the family members with 22q11.2 deletion syndrome. Clinical examination of the patients, their life story and pedigree and, along with routine clinical and biochemical analysis, and immune state testing, along with ultrasound imaging of thymus and thyroid glands, heart and abdominal cavity. We made conclusions that the phenotypic features associated with chromosome 22q11.2 deletion may be different for distinct family members. Further studies are required to determine length of deleted segment and the genes affected, as well as to establish the genotype-phenotype interactions and disease prognosis.