The immune processes associated with the formation of resistance to pathogens in the intestine depend on the microbiome. The maintenance of homeostasis in the intestine is provided by regulatory T-cells. In inflammatory bowel disease (IBD), both a disturbance of the T-regulatory function and changes in microflora are observed. Aggravation of the disease is accompanied by various infections. However, pathobionts such as Helicobacter spp., can affect regulatory T-cells. One of the genetic models for studying IBD is Muc2 knockout mice. In these mice, as in humans with IBD, intestinal epithelial and immune cells closely interact with the microflora. It is believed that the immune cells of the lymph nodes Muc2^-/- mice are sensitive to changes in the microflora formed in them. In this study, the effect of Helicobacter spp. on the number and percentage of different types of leukocytes and T regulatory cells in the mesenteric lymph nodes of Muc2^-/- mice was studied. The number of CD45⁺CD19⁺, CD45⁺CD3⁺, CD45⁺CD3⁺CD4⁺, CD45⁺CD3⁺CD8⁺-cells in the mesenteric lymph nodes of Muc2^-/- mice was significantly higher to compare with wild-type Muc2^+/+ mice. However, the presence of infection in Muc2^-/- mice canceled the increase in the number of CD45⁺CD19⁺, CD45⁺CD3⁺, CD45⁺CD3⁺CD4⁺, CD45⁺CD3⁺CD8⁺-cells. In wild-type Muc2^+/+ mice, infection had no significant effect on cells in mesenteric lymph nodes. This change in the decrease in immune cells in the mesenteric lymph nodes under the Helicobacter spp. may be associated with the activation of regulatory T-cells. Indeed, it has been shown that the presence of a congenital Helicobacter spp. infection increased of the number of regulatory T-cells (CD45⁺CD4⁺CD25⁺FoxP3⁺) in the mesenteric lymph nodes. Well known that regulatory T-cells mediate anti-inflammatory responses in the gut. Thus, an increase in regulatory T-cells promotes a decrease in all types of immune cells in the mesenteric lymph nodes of Muc2-/- mice infected with Helicobacter spp. It could provide an improvement in the vital functions of these mice and possibly reduces inflammatory responses in the intestine. This may indicate that some congenital pathobionts activate of the regulatory mechanisms of immunity and, thereby, have a beneficial effect on the host. 

Nanotechnology in immunology is a prospectively developing area in fundamental and practical medicine. Cucurbiturils are macrocyclic cavitands with a definite amount of glycoluril fragments (n) that determine the size of the cavity of these compounds. Nowadays, there are six synthesized homologues: 5, 6, 7, 8, 10 and 14. They differ from each other in the portal size and the size of the cavities. They are characterized by special physicochemical and biological properties, such as biocompatibility, stability, high ability to encapsulate chemical compounds. It is known that cucurbiturils encapsulate molecules by forming guest-host complexes, which allow the substance to be released from the complex and increase the solubility of the compounds. These advantages allow using cucurbiturils as drug delivery systems. Immunomodulatory activity of cucurbiturils depends on its specific nanoscale characteristics: functional groups, shape, size, surface, solubility in various media. Each nanoparticle depending on these properties has different effects on cells. The effects of cucurbiturils can be different even for one subpopulation of cells, depending on the homologue or dosage. The interaction of innate immune cells with cucurbiturils are not yet sufficiently characterized.

The aim of this study was to assess the effects of cucurbit[n]urils (n = 6, n = 7, n = 8) on innate immune cells – monocytes, NK-cells, NKT-cells.

The immunological recearch included the isolation of peripheral blood mononuclear cells from healthy donors (n = 8) on the density gradient of ficoll-urografin and flow cytometry with the determination of the amount of immunocompetent cells according to the classic markers of differentiation of these cells – CD3^- CD16⁺CD56⁺ for NK-cells, CD3⁺CD16⁺CD56⁺ for NKT-cells and CD3- CD14+ for monocytes. Monocyte activation was determined by the expression of surface HLA-DR.

The cells were cultured for 72 hours with the addition of cucurbiturils CB[6], CB[7] at concentrations of 0.1 mM, 0.3 mM, 0.5 mM and CB[8] at concentration of 0.01 mM, due to its poor solubility.

There were a significant decrease in the quantity of NK-cells (p < 0.01 for the test concentrations of CB[7]), an increase in the quantity of NKT-cells (p < 0.04 and p < 0.02 respectively for the concentrations of CB[6] and CB[7]). There was a tendency to increase the expression of HLA-DR on monocytes (p = 0.06 for CB[6]).

Considering a variative effects of cucurbiturils, in the future it is possible to consider a possibility of using cucurbiturils as an immunomodulators, antitumor agents, in autoimmune diseases. 

Glycodelin (PP14, PAEP, alpha-2-microglobulin, dimeric glycoprotein with molecular weight of 42 to 56 kDa) is considered as a reproductive tissue receptivity marker. Despite that glycodelin immunosuppressive effects are well-known there still remains uncovered its role in myeloid suppressor cell (MDSC) regulation. MDSC represent the heterogeneous population of immature myeloid cells that acquire suppressor phenotype while inhibiting the immune response under the pathological states. MDSC are known to play an essential role in supporting the immune tolerance in pregnancy and at transplantation. Our hypothesis suggests that glycodelin is capable of inducing the MDSC formation as the level of these cells is elevated during the successful pregnancy, whereas the spontaneous abortion and progression of eclampsia are associated with low circulating glycodelin. Therefore, the aim of the work was to analyze the role of recombinant glycodelin in physiological concentrations in regulation of MDSC differentiation. Peripheral blood mononuclear cells of donor volunteers were separated via centrifugation on density gradient of 1,077 g/cm3 (Ficoll-Hypaque, Sigma-Aldrich) to obtain MDSC generation in vitro. Then cells obtained were cultured in 24-well plate at a concentration of 1 × 106 cell/ml in complete medium with cytokines IL-6 (20 ng/ml), GM-CSF (40 ng/ml) therein for 14 days at 37 °C and 5% CO2. Medium replacement was made by 7^th day in culture followed by cytokine re-introduction, and on the 11^th day recombinant glycodelin in physiological concentrations (0,2; 2 mkg/ml) was applied while the pharmacological concentration was 50 mkg/ml. The M-MDSC (LinHLA-DRCD33⁺CD11b⁺CD14⁺CD66b^- ) and PMN-MDSC (LinHLA^-DRCD33⁺CD11b⁺CD14^- CD66b⁺) level was evaluated in cultures using flow cytometry (СytoFlexS (Beckman Coulter)) and “R&D Systems” antibodies according to standard protocol. Statistical data processing was realized with GraphPad Prizm software using Friedman test. It was found that glycodelin did not significantly affect cell viability being assessed with flow cytometry (PI). It was revealed that high GdA concentration (50 mkg/ml) being pharmacological did not render significant effect on MDSC differentiation. Meanwhile, glycodelin in concentrations correspanding the healthy pregnancy (0,2; 2 mkg/ml) was stated to increase the MDSC percentage in induced cultures of human mononuclear cells. When analyzing the subsets it was disclosed that this effect was conditioned by the increase in PMN-MDSC level while the M-MDSC level remained significantly unchanged. This result could be interpreted as glycodelin fetoprotective effect as the increase of the PMN-MDSC level is associated with the suppression of the immune response to paternal antigens. The PMN-MDSC level is known to be elevated in peripheral blood of healthy pregnant women at all the stages of pregnancy as compared to nonpregnant subjects whereas the M-MDSC amount remains unaltered. Meanwhile, patients with miscarriage demonstrated more that by 30% lowering in the MDSC amount in blood and endometrium and in I trimester, in particular. During the physiological pregnancy PMN-MDSC accumulate in placenta, but at spontaneous abortion their number is found to be declined. Placental PMN-MDSC efficiently suppress the T-cell response while concurrently polarizing the CD4+ lymphocytes in Th2 phenotype. PMN-MDSC are suggested to play an essential role in inducing and supporting the tolerance to fetal antigens that allows considering these as promising target of therapeutical manipulation in pregnancy complications. As a whole, we have originally demonstrated the GdA effect on MDSC differentiation. 

Graphene-based materials have an opportunity for use in biomedicine, thanks to their properties. Nevertheless, due to its cytotoxic effects, the use of graphene-based drugs is problematic. However, the surface modification of graphene oxide (GO) nanoparticles with a polyethyleneglycol (PEG) is one way to reduce the harmful effects of graphene on cells. Applying nanoparticles implies their interaction with the immune system, which protects the body. Monocytes are innate immunity cells and the first line of defenсe of the human organism from microorganisms and other alien objects. One of the monocytes’ reactions to a stimulus of any nature is to produce reactive oxygen species (ROS). Published data shows an incomplete picture of modified graphene oxide nanoparticles’ effects on ROS formation by human monocytes. Thus, it was essential to evaluate the pegylated graphene oxide (GO-PEG and GO-8armedPEG) effect on ROS production by human monocytes, assessed by the luminol-dependent chemiluminescence (LCL). The objects of the study were CD14⁺-cells isolated from mononuclear cells of healthy donors. ROS production was stimulated by opsonized zymosan (OZ), spontaneous LCL was used as a control. PEG-modified (GO-PEG and GO-8armedPEG) GO nanoparticles with sizes of 100-200 nm (“small”) and 1-5 μm (“big”) with PEG covering ~ 20% were used at concentrations of 5 and 25 μg/ml. The study showed that small size nanoparticles at a low concentration of 5 μg/ml and big nanoparticles coated with 8-armed PEG at both concentrations have a significant suppressive effect on spontaneous ROS production. In the stimulated LCL reaction variant, it was found that small nanoparticles (25 μg/ml) also have a suppressive effect on ROS production, such as big-sized particles coated with linear PEG at the same concentration. Thus, we have established for the first time that graphene oxide nanoparticles functionalized with PEG are capable of inhibiting the ROS production by human monocytes, and therefore, we can speak of the antioxidant activity of GO-PEG. 

Today transfection of mammalian cell with DNA or RNA construction is the only method for delivering programmed information into the cell nucleus. Electroporation is most commonly used method of transfection in experiments with dendritic cell. The aim of electroporation is to permeabilize the membrane by passing electric impulse through the cell. Due to the increase permeability of the membrane chance DNA or RNA construction getting inside into the cell is increased, wherein survival of the cells is decreased.

In the study male mice C57Bl/6 line 2-4 months old were used. From femur bones was isolated 20 × 106 bone marrow cells, which were cultured in 20 mL of complete RPMI-1640 for 7 days. To generate dendritic cells from BM cells, 100 ng/mL of rmFlt3-L was added to culture media at day 0. After 7 days of cultivation, the cell cultures were electroporated with control noncoding plasmids p5 (EP P5) or pmaxCCR9 encoding mouse chemokine receptor CCR9 (EP CCR9). The controls were cell cultures electroporated without any plasmids (mock EP) and cell cultures without electroporation (none EP). 5 × 105 cells were electroporated and resting for 10 minutes. After 10 minutes, cells were harvested and seeded into 24-well plates in 1 mL of culture medium and conditioning medium (1:1). Then, 50 ng/mL of Flt3-L was added to each well. The next day, transfected cells were collected and used for flow cytometry, qRT-PCR analysis.

It was found that after electroporation in the groups mock EP, EP P5, EP CCR9 relative amount of live CD11c+ dendritic cells was significantly less than in the non EP group. Moreover, in the EP P5 and EP CCR9 groups the frequency of live CD11c+ dendritic cells was significantly less than in the mock EP group. Expression of the CD86 marker in the EP P5 and EP CCR9 groups was significantly higher than in the non EP and mock EP groups. Expression of the I-AB(MHCII) in the EP CCR9 group on cDC2s was significantly higher than in the non EP group. On plasmacytoid DCs (pDCs) and conventional type 2 DCs (cDC2s) in the EP CCR9 group expression of CCR9 was significantly higher than in the non EP group. Therefore, in this study, we demonstrated the effectiveness of electroporation, accompanied by the decrease in the survival rate and maturation of DCs. 

While conducting numerous studies, including researchers in our laboratory, it was found that Th1/Th2 balance plays an essential role in the regulation of reactions that determine the outcomes of immunopathological processes in both chronic and acute GVHD models. However, the question about activity of which element in the regulatory process during GVHD induction (for example, a receptor or an enzyme) affects the ratio of this balance depends remains open. It has been suggested that the degree of activation of the GPR84 receptor during GVHD induction can significantly affect the host Th1/Th2 balance. And, by assessing this parameter, the direction of development and the intensity of the pathological process can be determined. The aim of this work was to investigate the effect of ligands such as medium-chain fatty acid receptor GPR84 on the Th1/Th2 balance in an experimental model in an in vivo system.

Female DBA/2 and hybrids (C57Bl/6 × DBA/2) F1 mouse strains were used in the experiments.The studied ligands of GPR84 were capric and lauric acids, as well as a synthetic ligand 6-OAU. Chronic GVHD in the semi-allogenic system was induced by injecting splenocytes from DBA/2 mice to B6D2F1 hybrid mice: 60-70 × 106 -cells iv twice with an interval of 6 days. The first administration of the GPR84 ligands was performed one hour after the donor cell transfer and then once a day for two weeks.The effect of the study drugs on the course of chronic GVHD was assessed three months after the onset of the experiment.

It was shown that the administration of GPR84 ligands to to animals during the induction of chronic GVHD affects the activity of the receptor and the host Th1/Th2 ratio. In the group with the injection of 6-OAU, the number of animals which the immunopathological process developed according to the Th1-dependent variant increased by more than 1.5-fold, compared with the control group. This fact is consistent with the literature data obtained in the in vitro system. Apparently, the effect of a mixture of capric and lauric acids is mediated by some other mechanism, differed from the GPR84 activation. Therefore, further research is required to realize the promising possibility of adjusting immune responses by including certain fatty acids in the diet.  

Аppearance of a malignant tumor is associated with impaired mechanisms of proliferation, differentiation, apoptosis ability. However, these changes are not enough for immune system to recognize and destroy mutated cells. Weak immunogenicity of tumor-associated antigens (TAA) and the insufficiency of co-stimulating molecules on the surface of tumor cells is a reason for this phenomenon Since biochemical processes of tumor cells and healthy tissue cells are identical, therefore creation of effective chemotherapeutic drugs is limited not by selectivity of their action. So antitumor vaccination is the most effective specific method for both preventing recurrence of a disease and a therapeutic treatment tool in oncology. Xenogeneic proteins are highly immunogenic and effective in breaking immune tolerance to human analogs. In our work, we used sheep testicular AG as a source xenogenic TAAs. Sheep testicles contain a large set of TAAs. Experimental mice were immunized with type liposomal testicular vaccine from sheep, one month after vaccination, to induce tumor growth, cells of carcinoma LLC were implanted in mouse. The life expectancy of the experimental group of mice was 2 times higher compared to the syngenetic control and 20% of them did not develop the tumor at all. In the spleen of mice who did not have tumors after pre-vaccination sheep liposomal testicular AG, T-regulatory cells and T-memory cells were measured. We found a credible decrease in both naive Treg (CD4⁺CD25⁺), activated (CD4⁺CD25⁺FoxP3⁺) and both T-memory (CD4⁺CD44⁺) and central memory (CD4⁺CD44⁺CD62L⁺) in spleen pre-vaccination mice with compared to the contral intact spleen. Content of IFNg and IL-10 in supernatants of mouse slenocytes derived from vaccinated mice with no tumors was investigated and showed a reliable decrease in the amount of IL-10, but not IFNg. We believe that immunization with xenogenic tumor AGs can lead to the formation of a protective antitumor response. 

Cytokines IL-7 and IL-15 are the most important humoral factors providing T-conventional cell pool reconstitution during homeostatic proliferation caused by lymphopenia. However, whether these cytokines can provide homeostatic maintenance and proliferation of T-regulatory (Treg) cells is largely unknown. Considering the association between homeostatic proliferation and the development of autoimmunity, we decided to investigate the ability of these factors to cause differentiation of Treg-cells into Th17-lymphocytes. Therefore, the purpose of this study was to investigate the influence of humoral factors of homeostatic proliferation (IL-7 and IL-15) on Treg-cells in vitro. The study used peripheral blood sampled from 22 healthy donors. PBMC fraction was isolated by Ficoll density gradient centrifugation. Proliferation was induced by IL-7, IL-15, and by a combination of IL-2 with anti-CD3-antibodies. The proliferation intensity of Tregs was evaluated by flow cytometry using CFSE in PBMC cultures by phenotype CD3⁺CD4⁺CD25⁺FoxP3⁺ and in the previously purified population of CD3⁺CD4⁺CD25⁺CD127lo-cells. In this case Treg-cells were obtained by immunomagnetic separation from PBMCs using a MACS Treg Isolation Kit. Also, the RORyt expression in CD3⁺CD4⁺CD25⁺FoxP3⁺-cells was evaluated during cultivation. Here, we have shown that IL-7 and IL-15 could support Treg-cells by number and phenotype. Also, we revealed that these factors provide FoxP3 expression in Treg-cells; meanwhile, stimulation with IL-2 + anti-CD3 can also cause induction of FoxP3 expression de novo in conventional CD4+ cells. Also, we have shown that IL-7 and IL-15 can cause lower-intensity proliferation of Treg-cells in comparison with IL-2 + anti-CD3. Herewith homeostatic cytokines didn’t have the ability to induce RORyt expression in both T-regulatory cells and CD4+ conventional T-lymphocytes. Thus, it has been shown that IL-7 and IL-15 can potentially participate in maintaining the total pool of Treg-cells during lymphopenia, when IL-2 deficiency occurs, without causing the induction of RORyt expression. However, how homeostatic cytokines affect the functional activity of Treg-cells remains unclear and requires further investigation. 

Macrophages play a key role in triggering and regulation of neuroregeneration. The characteristic feature of macrophages is pronounced plasticity, which manifests itself in the ability of macrophages to change their functional phenotype depending on the micromilieu. Apoptotic cell clearance (efferocytosis) is an important inducer of a macrophage polarization to M2 phenotype under pathological settings. Previously, we have developed an original protocol for the generation of M2-like macrophages, polarized by efferocytosis under serum-deprived conditions (M2 (LS), Low Serum). The present study was aimed to assess a neuroregenerative potential of M2 (LS) macrophages. We studied their effect on the differentiation of SH-SY5Y cells in comparison with retinoic acid (RA). As the morphological criteria of differentiation we have assessed the relative content of differentiated cells, i.e., cells with a neurite length exceeding the cell body length, and the average neurite length on days 3, 7, and 13. The ratio of neuron-like (N-type) and epithelial-like (S-type) cells in cultures was also assessed. SH-SY5Y cells were characterized by a low level of spontaneous differentiation, both under standard conditions (10% FBS) and serum deprivation (1% FBS). Upon RA treatment, SH-SY5Y cells stopped proliferating and underwent neuronal differentiation. Cultivation of SH-SY5Y cells in the presence of M2 (LS) conditioned medium also led to a significant increase in the relative content of differentiated cells, the average length of neurite-like processes, as well as a change in the balance of S- and N-type cells towards a pronounced predominance of the latter. The morphological features of differentiation were significantly less pronounced at early stage (day 3) of differentiation as compared with the RA-induced changes and reached the level of positive control only at later stages (day 13) (p < 0.05). In contrast to retinoic acid, M2 (LS) conditioned medium induced neuronal differentiation of SH-SY5Y cells without suppressing their proliferative activity. The data obtained may indicate a high neuroregenerative potential of M2 macrophages in vitro, which is realized through soluble factors and manifests itself in promoting SH-SY5Y differentiation. 

Mesenchymal stem cells which have both pluripotent and immunoregulatory functions are being actively studied as one of the treatment ways in many fields of medicine, including rehabilitation in nephrology. However, in some articles were dedicated to the treatment of different organic pathology with MSC’s was proved that the only reported effects from the application of MSC’s in regenerative medicine are that, after transplantation to damaged organs, in a paracrine manner they may inhibit apoptosis of cells, promote angiogenesis for a better blood supply, and in some cases stimulate cells that have survived in damaged tissues to proliferate in order to replenish dying tissue fragments. In other words, the pro-reparational functions were due to their paracrine effects without the impact of differentiation. Microvesicles are one of the components of this pro-regenerative effect. And although immunoregulatory action has been shown for MSCs, it remains poorly understood for microvesicles.

The aim of this study was to study the immunoregulatory properties of microvesicles (MSC-MB, MB) in comparison with mesenchymal stem cells (MSC). The experiment was carried out on CBA mice 3-4 months old, a model of glycerol-induced chronic renal failure (CRF) was used. MSCs were obtained from the bone marrow of syngeneic mice of the tibia and femur. MVs were obtained by apoptosis by culturing in a serum-free medium under oxygen deprivation conditions. MSC and MSC-MB were injected into the tail vein of mice; organs were harvested on the 11th day after administration of MSC and MSC-MB.

The state of cellular immunity in mice with chronic renal failure (CRF) after the introduction of mesenchymal stem cells (MSC) and microvesicles derived from them (MSC-MB) on the 11th day of the experiment was assessed by flow cytometry. As a result, there was a decrease in the number of T-regulatory cells CD4⁺ CD25⁺ Foxp3⁺, an increase in the content of CD4⁺ CD44⁺ CD62⁺ and CD8⁺ CD44⁺ CD62⁺ memory T-cells.

The effect of MVs was not significantly different from that of MSC. This may indicate that the therapeutic properties of MSCs are determined to a greater extent, if not completely, by MSC-MB. 

Aggression is a serious biomedical problem associated with a high percentage of patients and a lack of selective corrective agents. The most frequent increase in aggressiveness occurs in patients with depressive disorders, schizophrenia, reactive psychoses and adjustment disorders, which are known to be characterized by immunological dysfunction. Antipsychotics are widely used in the correction of psychomotor agitation; the antipsychotic effect of these drugs is manifested in the achievement of a sedative effect. However, like other psychoactive substances, they have a number of side effects that limit their long-term use and determines the need to search for new approaches to the correction of affective disorders. Experimental modeling of aggression is one of the main approaches for studying its pathogenetic mechanisms and searching for new effective therapeutic agents for the treatment. The study of the aggression pathogenetic mechanisms and the search for approaches to therapy within the framework of neuroimmune interaction is currently extremely promising. Currently, there is a large number of clinical and experimental data indicating interrelated changes in the functional activity of the nervous and immune systems during aggression. The leading links in the pathogenetic mechanism of aggression is the violation of the production and mutual regulation of cytokines, neurotransmitters, neuropeptides, growth factors, hormones, the effects of which are mediated by the cellular elements of the immune system. Given the immune cells essential role in the pathogenesis of aggression and the psychoactive substances unidirectional effect on the immune and nervous cells, make it possible to consider immune cells as model objects for influencing the intersystem functional relationship in order to edit the aggressive phenotype. The aim of the study was to investigate the effect of in vitro neuroleptic-modulated immune cells transplantation on behavioral phenotype and brain cytokines in aggressive syngeneic recipients. Aggressive behavior was formed in active male mice (CBA × C57Bl/6) F1 as a result of the experience of 20- fold victories in inter-male confrontations (distant sensory contact model). Aggressive mice splenocytes were treated in vitro with chlorpromazine and intravenously injected to syngeneic aggressive recipients. It has been demonstrated that modulated in vitro by chlorpromazine splenocytes of aggressive mice after transplantation edit the syngeneic aggressive recipient’s behavior against the background of a decrease in cytokines IL-1β, IL-2, IL-6, IFNγ and an increase in IL-4 in pathogenetically significant for aggression brain structures. The mechanisms of the aggressive behavior correcting effect of modulated immune cells are discussed. 

The immune and neuroendocrine systems play a critical role in maintaining a dynamic homeostasis in normal conditions and at mental maladaptation. Psycho- and immunopathology closely interrelated: pathological changes in the functioning of both systems occur simultaneously and are interdependent. Depression, as a mental disorder, is a major public health concern. The estimations are showing rise of the depression’s incidence in the future. However, currently used therapy of depression doesn’t provide a complete cure. It is known that a violation of neuroimmune interaction is an essential link in the pathogenesis of the disease, having a negative impact on its course, making the clinical picture worse, reducing effectiveness of the therapy, therefore, it’s urgent to search for a new treatment approaches. There are a sufficient amount data on the immune cells and their biologically active products leading role in the pathogenesis of depression. The unidirectional effect of most psychoactive substances on the central nervous system and the immune system confirms intersystem mutual regulation and allows considering the immune cells as model objects for influencing the intersystem functional relationship; so, cells immunotherapy can be the method of choice in the treatment of depressive disorders. We first demonstrated the possibility of animal’s behavior directed regulation by the transplantation of immune cells with definite functional characteristics, including those with functional activity modulated extracorporeally by a psychoactive substance. Based on the previous results we investigated the effect of the in vitro caffeine- treated immune cells on the behavior and immune phenotypes in depressive-like singeneic recipients. Transplantation of caffeine-treated splenocytes from depressive-like donors has been shown to induce depressive-like behavior editing in syngeneic recipients, which was manifested in anhedonia decrease, stimulation of exploratory behavior in the Open Field test and motor activity in the Porsolt forced swimming test. Recipient’s behavioral changes were registered on the background of decreased brain pro- inflammatory cytokines (TNFα, IL-1β, IL-6, IFNγ) and IL-10 increased in some pathogenetically significant for depressive-like state brain structures (hippocampus, hypothalamus, frontal cortex, striatum), which indicates a decrease in neuroinflammation. It was also detected recipient’s immune system functional activity modulation. The cytokines-mediated mechanisms of depressive-like behavior editing by the in vitro caffeine- modulated immune cells are discussed. 

Burn injuries are one of the key medical and social problems. Despite the significant achievements in combustiology, the slow healing and the appearance of infection are the key problems in burn patients, which lead to a longer hospitalization period, to reduction of life quality and to emotional disorders. Up to 70% of all complications after thermal trauma (TT) are connected with infection – first of all, pneumonia, infections of urinal tract. The forming of infectious complications, including sepsis, after TT is associated with excessive immunosuppressive reactions, as compensation for a long, stable proinflammatory response, in particular, owing to hyperproduction and effects of IL-10, IL-4, TGF-β. Aim: to study the influence of systemic and local usage of MT with original dermal film (DF) on reparation and serum cytokine concentration indicators in dynamics of experimental TT. The study was conducted using 84 rats – males of Wistar line, which were divided randomly into 4 groups: 1st group (n = 12) – intact monitoring, 2nd group (n = 30) – animals with TT, 3rd group (n = 21) – animals with TT and DF with MT use on the region of burn, 4^th group (n = 21) – animals with TT and intraperitoneal injection of MT. To model TT of IIIA degree and relative area 3,5%, isolated skin area of interscapular area was immersed in distilled water at a temperature of 98-99 °С at 12 s. The DF with MT (at a concentration of 0.005 g/g) on 12 sm2 – area in 3rd group was used daily for 5 days. The MT was injected intraperitoneally daily at the dose of 10 mg/kg for 5 days. The wound area was calculated, the interleukin-4 (IL-4), tumor necrosis factor alpha (TNFα), interferon-gamma (IFNγ) were determined in serum on 5^th,10^th and 20th day from the moment of TT induction in each group. During experimental TT in dynamic monitoring from 5^th to 20^th day the absolute and relative areas of wound defect are reduced, because of that the epithelization speed and its part of area reduction are progressively increasing, on 5^th,10^th and 20^th day the concentration of TNFα and IL-4 in serum is increasing with maximum values on 10th day of monitoring. Local usage of MT in DF during TT accelerates the healing of burn wound and lowers the TNFα and IL-4 concentration in serum on 5^th, 10^th and 20^th day. Intraperitoneal use of MT during TT accelerates the healing of burn wound and lowers the TNFα and IL-4 concentration in serum on 5^th and 20^th day. The reparation accelerating effect of MT during TT is more expressed in locale usage in DF rather than using intraperitoneal injection. 

The important role of immune disorders in recurrent miscarriage has been proven. Clarification of the character of B-lymphocyte differentiation and its regulation factors in women with threatened miscarriage and recurrent miscarriage in history is an urgent problem, since it will reveal the immune mechanisms of the pathogenesis of this pathology. Purpose: to establish the features of B-lymphocyte differentiation and factors of its regulation in women with a history of recurrent miscarriage and threatening spontaneous miscarriage at the time of examination.

Were examined pregnant women aged 18-40 years at a gestation period of 5-12 weeks. The main group consisted of 60 pregnant women with a threatening spontaneous miscarriage at the time of examination and a history of recurrent miscarriage. As a control, 35 pregnant women with uncomplicated pregnancy were examined. The comparison group consisted of 25 primary pregnant women with threatened spontaneous miscarriage at the time of examination. The material for the study was peripheral venous blood. Subpopulations of B-lymphocytes CD19⁺, CD19⁺ IgD⁺, CD20⁺IgM⁺, CD20⁺IgG⁺ were determined by flow cytometry; CD19⁺CD20^- CD38⁺, CD19⁺CD27^- , CD19⁺CD27⁺. Serum levels of BAFF and APRIL were assessed by enzyme-linked immunosorbent assay.

In the main group, an increase in the proportion of B-cells, CD20⁺IgM⁺-lymphocytes and memory cells was recorded in the peripheral blood, along with a decrease in the level of naive cells and plasma cells. In the comparison group, an increase in the proportion of immature IgM⁺B-cells, circulating memory cells, along with a decrease in naive B-lymphocytes, was registered. in the main group there was a pronounced decrease in the serum BAFF level compared with the control and comparison groups. Analysis of the APRIL content showed a pronounced downward trend in groups with threatened miscarriage relative to healthy pregnant women. Thus, threatening habitual and sporadic miscarriages were associated with a shift in the differentiation of B-lymphocytes towards immature forms and a lack of regulatory influence of BAFF and APRIL, which is reflected in the disruption of B-cell homeostasis and weakening of humoral effector mechanisms at the systemic level. The revealed changes may indicate a single mechanism for the development of a threatening spontaneous miscarriage, the severity of which increases with repeated loss of pregnancy. These changes can lead to an increase in effector cytotoxic mechanisms and an increase in proinflammatory cytokines, which can lead to the development of damaging reactions in the fetoplacental complex, which can be reflected in the clinical picture of the threat of termination of pregnancy. 

Rheumatoid arthritis (RA) is a frequent background for the development of renal pathology. Chronic kidney disease (CKD) is determined in more than 30% of patients with RA. Along with inflammation and other factors in the progression of the underlying disease, the development of renal damage in RA is facilitated by the presence of metabolic syndrome (MetS).

The aim of this study is to assess the relationship of serum concentrations of angiopoietin-like proteins (ANGPTL) and antiphospholipid antibodies (aPL) with the development of renal dysfunction in patients with RA.

We examined 158 patients with RA (91.8% – women and 8.2% – men) aged 21 to 80 years old and an average duration of the disease – 9 (4-15) years. The majority of patients were seropositive for rheumatoid factor and for antibodies to cyclic citrullinated peptide, with an advanced clinical stage and moderate activity (3.2 < DAS28 ≤ 5.1) of the pathological process.

The ELISA test was used for the quantitative determination of angiopoietin-like protein type 3 and type 4 and antibodies to phospholipids (aРL-IgG/IgM) for total detection of antibodies to cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidylic acid and a complex of negatively charged phospholipid and β₂-glycoprotein-I.

More than half of the examined RA patients had the calculated glomerular filtration rate (eGFR) ranging from 89 to 60 ml/min/1.73 m² (allocation by CKD stages: C1 – 21.5%; C2 – 58.9%; C3 – 19.6%). Signs of MetS (a combination of increased blood pressure, increased triglyceride levels and carbohydrate metabolism disorders against the background of central obesity) were diagnosed in 68 (43%) RA patients. Multivariable analysis of variance was performed to compare the studied parameters (ANGPTL3, ANGPTL4, aPL) depending on eGFR in groups of RA patients without signs of metabolic syndrome and RA patients with MetS. Significant differences in the level of ANGPTL3 (F = 8.86, p = 0.0034) and ANGPTL4 (F = 29.6, p < 0.001), but not aPL (p > 0,05) were found between RA patients with varying degrees of severity of metabolic disorders.

Multivariable analysis of variance showed a significant increase in ANGPTL4 in the blood serum of RA patients with reduced eGFR (< 89 ml/min) (F = 18.5, p < 0.001) and pronounced metabolic changes (F = 24.2, p < 0.001). Thus, only two factors (renal dysfunction and the presence of MetS) had a direct effect on the ANGPTL4 content in RA patients, which could describe the variability of this sign in more than 30% of cases. The squared multiple correlation coefficient (R2 ) in this model was 0.33. ANGPTL type 4 should be considered as a key factor linking the development of renal dysfunction and metabolic changes caused by rheumatoid inflammation. 

Much attention of researchers is directed to study the role of factors of homeostatic proliferation in the pathogenesis of autoimmune diseases, however, the effect of IL-7 and IL-15 on the phenotype of naive T cells  has not yet been sufficiently investigated in the pathology. The aim of this study was to investigate the proportion of CD45RA⁺ and CD31⁺ naive cells among CD4⁺ and CD8⁺ lymphocytes from healthy individuals and patients with rheumatoid arthritis (RA) upon stimulation with IL-7, IL-15 in vitro. In peripheral blood, we did not find any differences in the number of CD45RA⁺ and CD31⁺ cells between the group of donors and group of RA patients. In donors, stimulation by a combination of IL-7 with IL-15 promoted an increase in the proportion of CD4⁺CD45RA⁺ and CD8⁺CD45RA⁺  relative to their level in the peripheral blood. Whereas in RA patients the number of CD8⁺CD45RA⁺ cells decreased under IL-15 and the combination of IL-15 with IL-7 compared to the control without stimulation, and it, as a proportion of CD4⁺CD45RA⁺ cells, significantly differed from the content of these cells  under the same conditions in donors. There were no significant differences in the content of CD31⁺ cells and the number of CD31⁺ cells proliferating to cytokines, both between the groups of donors and patients with RA, and between different culture conditions. Thus, we can say that under the factors of homeostatic proliferation, there is a proportional increase in CD31⁺ T cells number, both in donors and in patients with RA. At the same time, naive T cells from donors  retain the expression of CD45RA during cultivation, while naive T cells from patients partially lose it. The obtained data  indicate that in RA, under  factors of  homeostatic proliferation  the phenotype of naive T cells is converted into the phenotype of memory T cells.

The key cellular and molecular factors being involved in the resolution of inflammation following acute myocardial infarction remain poorly understood. T-regulatory (Treg) lymphocytes are characterized by the extreme potential to regulate the strength and direction of immune responses during the myocardial injury. The functional activity of Treg-lymphocytes depends upon the transcription factor forkhead box protein P3 (FoxP3). It may be also expressed in conventional T-lymphocytes at the stage of their activation. Nuclear localization of FoxP3 is a prerequisite factor determining its ability to impact the suppressive functions of Treglymphocytes.

The aim of the present study was comparative evaluation of FoxP3+T-lymphocytes frequency and counts, combined with estimation of FoxP3 subcellular localization, in patients with acute myocardial infarction and chronic coronary syndrome and examination of changes of these parameters in the short-term follow-up of patients with myocardial infarction. The study included 14 patients with chronic coronary syndrome (8 males; 6 females; 63.2±9.0 y.o.) and 5 patients with acute anterior ST-segment elevation myocardial infarction (4 males; 1 female; 61.4±11.2 y.o.) at days 1, 3 and 7 after the event. The frequency of FoxP3⁺ conventional and regulatory T-lymphocytes was evaluated in peripheral blood mononuclear cells together with estimation of the level of FoxP3 nuclear localization by imaging flow cytometry.

Patients with infarction were characterized by the decreased counts of FoxP3⁺Treg-lymphocytes compared to patients with chronic coronary syndrome, and exhibited even further decrease in the counts of FoxP3⁺Tregcells at day 7 after infarction, while frequency of Treg and conventional T-lymphocytes did not differ significantly. The level of FoxP3 nuclear translocation was lower both in Treg and conventional T-lymphocytes in patients at day 1 post-infarction compared to patients with chronic coronary syndrome. Absolute counts of FoxP3⁺Tregs with nuclear FoxP3 localization remained significantly lower both at days 1 and 7 post-infarction compared to patients with chronic coronary syndrome.

Thus, here we demonstrated that FoxP3 nuclear localization experiences decrease in the course of acute myocardial infarction and may serve as a more sensitive marker of changes in Treg-lymphocyte functioning than simple evaluation of their frequency. 

Determination of interrelationships between impairments of laboratory parameters of immune and metabolic status in patients with chronic cerebral ischemia of I-II stages was carried out. The study included 104 patients, of which 76 were female and 28 males, with CCI on the background of II degree hypertension, of which 52 patients were with stage I and 52 with stage II at the age of 50 ± 5 years. Also, clinical and laboratory parameters were studied in 22 healthy donors of the same age. Evaluation of clinical and laboratory data was carried out at the beginning of treatment and 2 weeks after its end. The sorption capacity of erythrocytes and the sorption capacity of the glycocalyx (SEG), the activity of lipid peroxidation processes, the state of the antioxidant system were determined in blood plasma and erythrocytes, the level of stable metabolites of nitric oxide (SMNO), neopterin, C-reactive protein, cytokines (TNFα, IL- 1β, IL-8, IFNγ, IL-18, G-CSF, IL-4, IL-10), immunoglobulins (IgM, IgG, IgA), complement system components (C3, C4, C5, C5А), the phagocytic and oxygen-dependent activity of polymorphonuclear blood leukocytes. Comparative assessment of the results of correlation, factorial and cluster analyzes for assessing the parameters of the immune and metabolic status in patients with stage I CCI revealed the most significant laboratory parameters necessary for determination in the clinic for objective assessment of the severity of immune and metabolic disorders: TNFα, IL-8, IL-10, SMNO and NEG. In patients with CCI stage II, to objectively assess the severity of immune and metabolic disorders, TNFα, IL-8, IL-17, IL-10, the phagocytic number of neutrophils and SEG are recommended. 

The aim of this work was to study some parameters of cellular immunity in patients with multiple sclerosis (MS). The study included 10 patients with relapsing-remitting MS aged 32 to 50 years. Diagnosis was clinically established and confirmed by magnetic resonance imaging. Patients did not receive immunosuppressive therapy for at least 6 months prior to study entry. The neurological status of all examined patients was assessed using the Kurtzke functional scale using the Extended Disability Scale (EDSS) and averaged 4.0±0.67 points, the mean number of exacerbations per year was 1.25±0.25. While studying such parameters of the immune status such as the number of T, B, NK-cells, the content of immunoglobulins, the phagocytic activity of monocytes and granulocytes, their production of reactive oxygen species, no significant differences were observed in patients with MS in comparison with the normal donor level. At the same time, we have noted an increase in the proliferative response of mononuclear blood cells to myelin antigen by 2.35 times. The content of CD4⁺CD45RO⁺CD62L⁺ and CD8⁺CD45RO⁺CD62L⁺ central memory T-cells, as well as CD8⁺CD45RO⁺CD62L^- effector memory T-cells in the blood of MS patients significantly exceeded the control values (p < 0.05). Also, in MS patients, compared with healthy individuals, there was an increased level of naive IFNγ-positive CD4⁺CD45RO^- and CD8⁺CD45ROT-cells (p < 0.01), and an increase in CD4⁺CD45RO⁺ and CD8⁺CD45RO⁺ memory T-cells producing IFNγg or IFNγg together with IL-4 in response to the activation (p < 0.01). Consistent with these data, there were significantly increased serum IFNγ and IL-17 levels and no changes in IL-4 levels. The relative level of naive CD4⁺CD25⁺FoxP3⁺, as well as induced CD4⁺CD25^- FoxP3⁺ regulatory T-cells in MS patients did not significantly change compared to donor values. The results of assessing some parameters of the immune status in MS patients indicate a functional reshaping of the immune system towards the Th1 type of immune response. It is obvious that immunotropic treatment of MS should be aimed at inactivating auto-immune Tand B-lymphocytes, suppressing the production of proinflammatory mediators, and enhancing the activity of natural and induced regulatory T-cells. 

Considering to the data of class I human endogenous retrovirus HERV-Е λ 4-1 subgroup association with multiple sclerosis, an autoimmune disease accompanied by neuroinflammation, changes in the neurotransmitters level, progressive neurological dysfunction, as well as the ability of this retrovirus to replicate and to produce proteins with potential immunomodulatory properties, the aim of this work was a comparative study of the blood immune cells cytokine synthesizing function in conventionally healthy individuals and multiple sclerosis patients under the synthetic 17 – amino acid oligopeptide homologous to the hydrophobic transmembrane protein р15Е HERV-Е λ 4-1 conserved region influence. The 40 patients, 17 male persons aged 38.0 (31.0-47.0) years old and 23 female persons aged 39.0 (31.0-50.0) years old with an established diagnosis of multiple sclerosis (G 35, ICD-10), corresponding to the McDonald 2005, modified in 2010 criteria with a continuously progressive disease course and the disease duration of 17.0 (14.0-18.0) years, and 30 conditionally healthy individuals, 12 male persons aged 32.0 (23.0-43.0) years old and 18 female persons aged 36.0 (29.0-46.0) years old were the objects of the study. An open-label, observational, single-center, cohort, controlled, randomized trial was conducted. It was found that the donor’s blood mononuclear cells IL-1β, IL-6, TNFα, IFNγ and IL-2 spontaneous production in culture was stimulated, but that of IL-4 and IL-10 did not change under the retroviral oligopeptide influence. At the same time, the spontaneous and mitogenstimulated production of all studied cytokines did not change under the control oligopeptide influence. The PHA-stimulated donor’s blood mononuclear cells cultivation in presence of the retroviral oligopeptide, as compared to the control one, was accompanied by an increase in the IL-1β, IL-6 and TNFα release into the culture supernatant. The multiple sclerosis patients were characterized by IL-1β, IL-6 and IFNγ higher content in the mitogen-unstimulated blood mononuclear cells culture supernatant, compared with conditionally healthy individuals, as well as by a higher production of IL-6 and IFNγ in response to PHA stimulation. The retroviral oligopeptide, in contrast to the control one, stimulated the IL-1β, IL-6, TNFα and IFNγ spontaneous production without altering that of IL-4 and IL-10 in multiple sclerosis patients. The obtained results indicate that the synthetic oligopeptide homologous to the conserved region of the hydrophobic transmembrane protein p15E HERV-Е λ 4-1 has the pro-inflammatory properties, which is probably the one of human endogenous retrovirus HERV-Е λ 4-1 pathological abilities realization mechanism in multiple sclerosis. 

Currently, in the pathogenesis of recurrent miscarriage, a special role is given to immunological factors, in particular the role of innate immunity. The aim of the study was to assess the relative content of monocytes in the peripheral blood producing IL-4, IL-6, IL-10, IFNγ, as well as to identify new criteria for predicting the outcome of pregnancy in women with the threat of early termination and recurrent miscarriage. Materials and methods. 88 pregnant women at 5-12 weeks’ gestation were examined, the main group consisted of 59 women with recurrent miscarriage and threatened miscarriage at the time of the study, the control group – 29 women with uncomplicated pregnancy without recurrent miscarriage. The main group, depending on the outcomes of pregnancy, was subdivided into subgroups: subgroup I – 42 women whose pregnancy ended in timely delivery, subgroup II – 8 women with preterm labor, subgroup III – 9 women with abortion up to 22 weeks (spontaneous miscarriage and non-developing pregnancy). In the control group, all women had a timely delivery. Research material – peripheral venous blood. The relative content of IL-4⁺, IL-6⁺, IL-10⁺, IFNγ+ monocytes was assessed on a FACSCanto II flow cytometer using monoclonal antibodies. Statistical data processing was carried out using a package of standard applied programs. Results. In the group of women with recurrent miscarriage and threatened miscarriage, the relative content of IL-10⁺ and IL-4⁺ monocytes was reduced and the content of IL-6⁺ monocytes was increased compared to the control group (p = 0.0001 in all cases). There were no statistically significant differences in the content of IFNγ⁺ monocytes in the compared groups (p = 0.069). With a relative content of IL-4⁺ monocytes equal to 26.7% or less, preterm labor is predicted. With a relative content of IL-10+ monocytes equal to 27.0% or less, abortion (spontaneous miscarriage or miscarriage) is predicted in gestational age up to 22 weeks. An increase in the ratio of IFNγ⁺/ IL-4⁺, IFNγ⁺/IL-10⁺, IL-6⁺/IL-4⁺, IL-6⁺/IL-10⁺ monocytes was found in the main group (p < 0.0001 in all cases ). Conclusions. In women with recurrent miscarriage in all subgroups, the level of M1 monocytes prevailed over the level of M2 monocytes. The data obtained allowed the development of new prognostic criteria for termination of pregnancy up to 22 weeks and premature birth. 

Steatosis in the liver in obesity increases the work of mitochondria to utilize excess lipids. An overload of β-oxidation of fatty acids, the tricarboxylic acid cycle, and oxidative phosphorylation leads to a decrease in ATP and an increase in the formation of reactive oxygen species. Normally, mitochondria can efficiently remove elevated levels of reactive oxygen species using the cell's antioxidant system and metabolic adaptation to altered conditions. This study aimed to investigate the role of hepatic SOD expression in the pathogenesis of NAFLD in obesity. It was found that the level of SOD1 expression in the liver in obese patients with and without type 2 diabetes with a BMI > 40 kg/m2 was lower than in healthy donors. The copy number of mitochondrial DNA (mtDNA) in the liver in all obese patients was more than two times lower than in the control group. In the liver of obese patients without type 2 diabetes, the SOD1 protein level and the mtDNA copy number were interrelated and negatively correlated with the area of fatty inclusions. Thus, in obese patients, a decrease in antioxidant defense in the liver leads to the vulnerability of mitochondria, which, in turn, contributes to the progression of steatosis and insulin resistance.

Behcet’s disease (BD) is a systemic autoinflammatory-autoimmune disease (chronic systemic vasculitis) of unknown etiology, almost 70% of patients develop uveitis. BD pathogenesis is complex, human herpesviruses (HHV) play an important role among infectious trigger factors. Ability of herpesviruses to modulate cytokine production and evade host’s immune response is known.

Aim of the study was to assess the effect of Herpes simplex virus type 1, Herpes simplex virus type 2, Cytomegalovirus, Epstein-Barr virus on systemic levels of chemokines, pro- and anti-inflammatory cytokines in BD with and without uveitis. Serum samples were collected from 116 BD patients chronically infected with HHV and examined in ELISA-test for markers of HHV reactivation (IgG-antibodies to immediate early HSV antigens 1, 2 and CMV, early EBV antigen). Concentration of IL-1β, IFNγ, MCP-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, IL-18, TNFα, GMCSF, Eotaxin, GRO-α, IP-10, MIP-1α, MIP-1β, SDF-1α, RANTES detected in multiplex analysis. TGF-β1, TGF-β2 were measured in ELISA-test. Depending on presence and activity of uveitis 3 groups of patients with BD were identified: group 1 – active uveitis, group 2 – remission of uveitis, group 3 – BD without ocular manifestations. After serological study 2 subgroups were highlighted in each group: a) patients with antibody markers of reactivation of at least one HHV, b) patients chronically infected with HHV, without serological signs of reactivation. Mean level and detection rate of cytokines and chemokines in patients with active uveitis (1a, 1b) and in remission (2a, 2b) were compared with patients without eye damage (3a, 3b). Chronic HHV infection (subgroup “b”) was compared with reactivation (subgroup “a”). A significant increase of MCP-1/ CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, IP-10, SDF-1α chemokines in serum, as well as IFNγ, TGF-β1, and TGF-β2 was observed in patients with uveitis (regardless of their activity) and HHV reactivation compared to patients without uveitis. Our data indicate that systemic production of cytokines and chemokines in BD patients and uveitis could be affected by the activity of chronic herpesvirus infections, and the greatest changes are related to chemokines. 

The complexity of the adipogenesis mechanism results from the impact of multiple cues, among which an important place is held by the components of the Wnt signaling pathway. The search for potential markers of the development of diseases related to obesity aroused an interest in the study of GSK-3 (glycogen synthase kinase), β-catenin. GSK-3β is an intracellular serine / threonine kinase found in the cytoplasm, nucleus, mitochondria, synthesized in all body tissues and involved in regulating metabolic processes, cell proliferation, apoptosis etc. The first of the discovered functions of GSK-3β was the regulation of glycogen synthesis. Active GSK-3β phosphorylates and thereby inhibits glycogen synthase. As a result of the insulin binding to the cell receptor via inositol-3-phosphate, protein kinase B (Akt1) is activated, which, in turn, phosphorylates and inhibits GSK-3β. In addition, GSK-3β is involved in the regulating glucose metabolism. The most important function of GSK-3β is the inhibition of the β-catenin protein. In a resting cell, GSK-3β in complex with the APC and Axin proteins binds and phosphorylates the β-catenin transcription factor, which leads to its ubiquitination and degradation. When Wnt proteins act on the cell, the Dvl protein is activated, which, by binding to GSK-3β, releases β-catenin, preventing its degradation, however, the role of GSK3α/β in the adipocyte inflammatory response has not yet been fully investigated, therefore it seems promising to study the role of GSK-3 in the Wnt/β-catenin signaling pathway in obesity

The aim of the study was to assess the activity of the components of the Wnt signaling pathway in obese patients by measuring the serum level of GSK-3 and β-catenin. There were enrolled 32 patients with progressive forms of I-III degree obesity in the absence of diabetes mellitus. The concentration of serum GSK-3α, GSK-3β, and β-catenin was measured by enzyme-linked immunoassay. Data are presented as absolute and relative (%) number of patients; arithmetic mean; medians, 1 and 3 quartiles – Ме (Q0.25-Q0.75). Obese patients contained a 7.5-fold increased serum level of GSK-3α (785 (371-1317.5) pg/ml) compared to healthy individuals 105 (102.5-110) pg/ml, (p < 0.001), paralleled with increased amount of GSK-3β, which level in obese patients was 295 (190-695) pg/ml, which is by 18.3% higher than those in healthy individuals 241 (218.75-287.5) pg/ml, p = 0.111. Amount of GSK-3 depending on the degree of obesity tended to increase, most often coupled to decreased β-catenin level which is consistent with the literature data and can be considered as a prognostic criterion for the course of pathological processes in obesity. 

Due to the general trend of changes in reactivity in many exogenous and endogenous diseases, more and more attention is currently being paid to changes in immunological reactivity in drug addiction. The expediency of assessing the state of immune mechanisms in opioid addiction is determined by the need to predict their course and outcome. The aim of the study was to study the immunological reactivity of the body in patients with opium addiction in a stage of abstinence. For this purpose, clinical and immunological studies were conducted in 80 patients who use opioid drugs. The duration of the disease ranged from 0.5-19 years. Of these, the disease duration is up to 3 years – 28 patients (group I), and over 3 years – 52 patients (group II). The number of subjects in the control group was n = 50. Authors carried out the assessment of the mental, narcological, somatic, and neurological status. In addition, they have studied the general clinical, biochemical and immunological parameters As a result of this study, it was found, that patients of group I had more pronounced T-lymphocytopenia. A persistent increase in the value of serum IgM was revealed both in the dynamics of abstinence and depending on the duration of the disease, which may indicate a strain on the humoral link of immunity in opium addiction. In addition, as the duration of chronic narcotization increases, there is a tendency to increase the relative number of B-lymphocytes. Thus, at the patients with opium addiction in a state of abstinence develop T-lymphocytopenia. Moreover, with an increase in the duration of the disease, an increase in the level of IgM by 2-2.6 times. The revealed changes in the immunological reactivity of the organism suggest the need to include immunocorrective therapy in the complex of therapeutic measures for opium addiction. 

The NF-κB transcription factor controls the expression of genes responsible for cell cycle, apoptosis, and other immunoregulatory functions. Some nonspecific NF-κB inhibitors were found after discovering the possibility of blocking tumor growth through suppression of NF-κB activity, but their use was complicated by multiple side effects, such as interleukin-1β-related systemic inflammation or non-immunerelated complications, which may be due to inhibition of the p65 NF-κB subunit that plays a central role in organogenesis and inflammation. Inhibition of the c-Rel subunit leads to tumor growth restriction by modulating the T-regulatory cell activity.

In 2017, Grinberg-Bleyer and co-authors checked the hypothesis that selective inhibition of the c-Rel subunit can be performed using pentoxifylline and will effectively regulate Treg activity during tumor growth. The authors showed that pentoxphylline, an FDA-approved drug, could indeed induce selective degradation of c-Rel without affecting p65, and suggested that such an effect could be effective in suppressing tumor growth. In this regard, we aimed to investigate in vitro how pentoxifylline affect the functional activity and antitumor cytotoxic potential of T-cells in cancer patients.

The objects of the study were peripheral blood mononuclear cells from 25 patients with primary breast cancer (no metastases), 15 patients with metastatic breast cancer, and 25 healthy women without breast pathology. Informed consent was obtained from all donors and patients. The study was approved by the local ethics committee.

Here we showed that pentoxifylline treatment in vitro enhances the pro-apoptotic and cytotoxic antitumor response via increasing the expression of TRAIL on T-lymphocytes, mainly in healthy donors and patients with metastatic breast cancer, both on intact T-cells and in response to the cells of the tumor line of human breast carcinoma ZR-75-1. In healthy donors, in the presence of pentoxifylline, a population of highly expressing TRAIL CD4 and CD8 T-cells appears. 

Various immune cells as well as related cytokines are involved in immunopathogenesis of sarcoidosis and mechanisms of granuloma development. Currently, a role for chemokines in sarcoidosis has been extensively investigated, which is paralleled with a search for key molecules necessary for recruiting immune cells to intrusion site and granuloma formation as well as affecting outcome of the latter. Our study was aimed for determining level of plasma CCL17/TARC and CCL22/MDC chemokines in patients with sarcoidosis who received no immunosuppressive therapy is of high priority for clarifying some aspects in underlying immunopathogenesis as well as seeking out for secure clinical and laboratory criteria for assessing activity and disease prognosis. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 52). In 37% (19/52), they exhibited acute clinical manifestations, and 63% (33/52) had chronic sarcoidosis. The control group included peripheral blood samples from healthy volunteers (n = 22). The chemokine concentrations (pg/ml) were determined by multiplex analysis using xMAP technology (Luminex), and Milliplex MAP test system (Millipore, USA). In the patients with sarcoidosis, significantly higher levels of chemokines were shown relative to healthy volunteers: CCL17 – 78.24 pg/ml vs 26.24 pg/ml, p < 0.001; CCL22 – 660.60 pg/ml vs 405.00 pg/ml, p < 0.001. Evaluation of clinical and laboratory diagnostic characteristics for plasma chemokine levels in sarcoidosis patients allowed to assess their sensitivity and specificity. The respective values were as follows: in acute sarcoidosis: for CCL17 – 63% and 78%, CCL22 – 63% and 91%; in chronic sarcoidosis: CCL17 – 58% and 83%, CCL22 – 67% and 86%, respectively. In chronic sarcoidosis the levels of this chemokine correlated with the activity of angiotensin-converting enzyme (ACE), for CCL17 (r = 0.530; p = 0.003), for CCL22 (r = 0.446; p = 0.014). Patients with systemic lesions vs no systemic lesions (sarcoidosis of the respiratory system only) had significantly elevated CCL17 level: 102.82 pg/ml vs 32.72 pg/ml, p = 0.011. The concentration of chemokine CCL17 was significantly increased in patients with vs without signs of hepatomegaly: 130.73 pg/ml vs 51.60 pg/ml, p = 0.022. Levels of chemokines was significantly increased in patients with vs without ultrasound signs of splenomegaly comprising: for CCL17 – 249.18 pg/ml vs 46.87 pg/ml, p = 0.002; for CCL22 – 1271.40 pg/ml vs 660.63 pg/ml, p = 0.003. Thus, it should be noted that the peripheral blood plasma level of chemokines CCL17 and CCL22 may be used as additional prognostic markers in chronic sarcoidosis with varying scoring of clinical signs including with/without systemic disease manifestations. 

Subject: to assess a role of factors of innate and adaptive immunity in the development of intrauterine generalized cytomegalovirus infection.

The study included 47 newborns with congenital generalized cytomegalovirus infection comprising group I. Based on the data of clinical and laboratory examination, all newborns studied were divided into two subgroups. Subgroup 1.1 (29 subjects) consisted of newborns with severe CMVI and subgroup 1.2 (18 subjects) – newborns with moderate CMVI. The control group included 26 newborns without herpesvirus infection.

Determination of the number of monocytes expressing Toll receptors (TLR) was performed by laser flow cytometry (Beckman Coulter) using Beckman Coulter, HyCultBiotechnology reagents: FITC-CD282+, CD284+, CD286+, and PE-CD14+. The newborn serum concentration of IFNγ, IFNα, IL-6, IL-8 was determined by ELISA using BenderMedsistems test systems.

Intrauterine generalized CMVI with complete clinical symptoms in newborns was characterized by a decrease in the number of monocytes expressing TLR-2 and TLR-6, which was associated with a decrease in the level of IFNα, IFNγ, an increase in the level of IL-6, IL-8 and MCP-1. The subgroup with incomplete clinical symptoms CMVI was characterized by a decrease in the level of IFNα, in combination with an increase in the level of IL-6. The identified immune disorders lead to a reduction in the antiviral immune response and determine the severity of the disease in prenatally infected newborns. 

Alzheimer’s disease (AD) is currently the most common cause of dementia. A significant role in the pathogenesis of AD belongs to the activation of the mechanisms of neuroinflammation. There is a hypothesis that chronic infections may play a role in the maintenance of the inflammatory response in AD. The aim of this work was to study the detection rate and DNA level of herpesviruses, as well as their possible relationship with the level of the key cytokines and with clinical parameters of AD in patients with early and late onset. 30 patients with AD and 33 healthy volunteers were enrolled. The quantitative determination of DNA of CMV, EBV, HHV-6, HHV-7 was carried out by PCR. The level of cytokines and soluble IL-1β antagonist (IL-1ra) in the blood was determined by ELISA. Herpesvirus infection with increased viral load was determined if at least one of the criteria was present: 1) DNA level of EBV and/or HHV-6 > 10,000 copies/ml in saliva; 2) presence of DNA of at least one of the EBV, HHV-6, HHV-7 viruses in the blood. In the subgroup of patients with early onset and increased viral load, there was a higher increase in the levels of a number of cytokines: proinflammatory IL-8 and IL-12, a Th2-cytokine IL-4, a cytokine of the adaptive immune response IL-2. However, the level of the anti-inflammatory protein IL-1ra was lower than in the controls. These changes may indicate a dysregulation of the antiviral response, with a predominance of activation of systemic inflammation and Th2-mediated reactions. Also, in early onset AD the increased viral load was associated with lower scores on Boston naming test. The results indicate that in studies of AD mechanisms and in the search for prognostic markers of the disease, it is important to take into account the heterogeneity of AD in terms of genetic predisposition factors, risk factors, immune parameters and clinical data. Such approach is necessary for the subsequent development of personalized approaches to the prevention and treatment of AD. 

Degenerative-dystrophic retinal diseases, particularly age-related macular degeneration (AMD), are now considered to be the lead cause of blindness and low vision in developed countries, with a steadily increasing trend. Recent publications provide evidence for the involvement of inflammatory mechanisms in TMD development and progression unveiled due to advances in innate and adaptive immunity research. However, the immunopathogenesis of atrophic AMD form, “geographic atrophy” (GA) remains largely unstudied. Objective: to investigate local mRNA expression of inflammatory cytokines IL-1β, IL-18, CCL2/MCP-1 in a model of RPE atrophy induced after subretinal injection of 0.9% sodium chloride solution in experimental rabbits. The investigation was carried out in tissue complex retina-RPE-choroid (TC) samples isolated from eyes of 23 albino New Zealand rabbits after modeling RPE atrophy by subretinal injection of 0.9% sodium chloride solution and 5 healthy rabbits lacking eye lesions. Animals in the experimental group (one week before surgical intervention, in the early period, and in the period of sustained RPE atrophy formation) and controls were subjected to optical coherence tomography (OCT) and ocular fundus autofluorescence (FAF). Evaluation of proinflammatory cytokine gene expression levels in TC was performed by RT-PCR. Results. Subretinal injection of 0.01 ml of 0.9% sodium chloride solution induced experimental RPE atrophy development in rabbits vs. control that was associated with multidirectional changes of IL-1β, IL-18, MCP-1/CCL2 gene mRNA expression. Three types of response in the TC, formed during development of atrophic changes and determined by the value of local cytokine gene expression were characterized: 1) hypo/ no response – decreased/no expression; 2) normal response – moderate increase; 3) hyper response – overexpression. 69.6% of animals with persistent atrophy had a moderate to hypertrophic increase in locally expressed mRNA MCP-1/CCL2, whereas 30% cases had significantly increased IL-1β mRNA expression – factors damaging the blood-retinal barrier and contributing to posterior segment immune privilege. It should be taken into account while developing new strategies for treatment of ophthalmic pathology, in particular the currently actively studied and tested options for RPE stem cell transplantation into subretinal space. The data obtained may be useful to investigate various types of RPE atrophy and develop new strategies of ophthalmopathology treatment in preclinical studies. 

Treatment of young children with atypical or recurrent purulent soft tissue infections (PSTD) that do not respond well to surgery and antibiotics is most challenging. PSTD occurs against the background of impaired functioning of the immune system and, first of all, the system of neutrophilic granulocytes (NG). The vector effect of immunotropic therapy on a specific NG subsets may allow the correction of NG dysfunctions without compromising host protection, including strategies to enhance, inhibit or restore their functions.

The aim of study: to evaluate in vitro the modulating effects of arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine (HP) on the transformed phenotype of 4 NG subsets, as well as on the functional activity of NG in children with purulent-inflammatory soft tissue diseases.

We studied samples of peripheral blood (PB) from young children 2-4 years old: 17 children with atypical acute PSTD and 10 apparently healthy children. At stage I, a comparative assessment of the content and phenotype of 4 NG subsets CD16⁺CD62L⁺СD63^- , CD16⁺CD62L⁺СD63⁺, СD64^- CD16⁺CD32⁺CD11b⁺, СD64⁺CD16⁺CD32⁺CD11b⁺, phagocytic and microbicidal functions of NG was carried out. At stage II, the in vitro system determined the effects of HP on NG in children with PSTD according to the studied parameters. By the method of flow cytometry (FC500 “Beckman Coulter” (USA), conjugates of MkAT “Beckman Coulter International S.A.” (France)), the relative number of NGs of the studied subsets and the density of receptor expression (MFI) were determined. To assess the phagocytic function of NG a microbiological method was used to assess the completeness of phagocytosis with S. aureus (strain 209). The activity of NG NADPH oxidase was investigated in the NBT-spontaneous test (NBTsp.) and in the in vitro NBT-induced test (NBTind.). A comparative study of PB samples from conventionally healthy children and children with PSTD made it possible to identify various variants of transformation of the phenotype of the studied NG subsets, associated with defects in their functional activity. In the in vitro system the effects of HP were demonstrated, manifested by a decrease in the amount of CD16⁺CD62L⁺CD63⁺NG and an increase in CD16⁺CD62L⁺CD63^- NG, modulation of the negatively altered phenotype of subsets CD64^- CD32⁺CD16⁺CD11b⁺NG and CD64⁺CD32⁺CD16⁺CD11b⁺NG, aimed at restoring phagocytic function and maintaining the tension of NADPH oxidases.

As a result of the study it was found the immunomodulatory effects of HP, which is manifested in the reorientation of NG from the pro-inflammatory phenotype to the anti-inflammatory one, which can be used in the future when creating personalized targeted immunotherapy aimed at correcting defective functioning NG in early children, suffering from PSTD. 

Traumatic brain injury (TBI) is one of the most common pathologies of the central nervous system in the world, and the use of structural neuroimaging methods – computed tomography (CT) and magnetic resonance imaging (MRI) – often doesn’t allow assessment of the severity of the brain injury that has occurred. This situation predetermines the need to search for new methods of differential diagnosis of the severity of TBI and predicting the risk of consequences.

One of these promising areas is the study of the immune status, since traumatic brain injury is characterized by a high rate of complications.

One of these promising areas is the study of the immune status in patients with TBI in the acute period. It is now known that in response to brain damage, a response from the immune system is triggered.

The reactions from the immune system, which develop after brain injury and directed against its own antigens, in the early period of the disease are related to damage to the nervous tissue. However, according to the latest available data, they are subsequently able to stimulate the processes of repair and regeneration in the brain tissue. In the course of damage to the nervous tissue, in response to endogenous molecules formed during the destruction of cells and the extracellular matrix, the cells of the immune system are activated.

Current evidence indicates that T-cells play a role in both the formation of secondary damage and repair mechanisms. They are able to protect neurons through the production of neurotrophic factors such as brain neurotrophic factor (BDNF), which stimulates the growth of neurons, the formation of synapses.

Using multicolor cytometric analysis within the framework of this work, a study was carried out to determine the number of the main subpopulations of CD3⁺CD4⁺-lymphocytes. The relative number of Th17 (CXCR5^- CXCR3^- CCR6⁺CCR4^- ) and Th17/Th22 (CXCR5^- CXCR3^- CCR6⁺CCR4⁺), Th1/Th17 (CXCR5^- CXCR3⁺CCR6⁺CCR4^- ) among total CD45RA-negative CD3⁺CD4⁺-cells population is significantly increased in comparison with the values in the control group, in turn, the Th1(CXCR5^- CXCR3⁺CCR6^- CCR4^- ) subpopulations among total CD45RA-negative CD3+CD4+-cells are significantly decreased with the values in the control group. The results obtained so far make it possible to consider immune responses among the key links in the pathogenesis of brain contusion TBI. And, perhaps, a comprehensive immunological examination of the victims in the first day after the injury will determine the parameters that will help predict the nature of possible complications in patients with brain contusion. 

Synthetic materials used in regenerative medicine, upon implantation, induce the development of an inflammatory reaction necessary for the effective regeneration of damaged bone tissue. Implant contact with tissues is accompanied by the deposition of blood proteins and interstitial fluid on its surface, contributing to the activation of the complement system, components of innate immunity, initiating coagulation hemostasis, leading to the formation of a fibrin clot. An extracellular matrix based on fibrin, collagen and elastin forms on the implant’s surface, which provides the basis for the formation of tissue structure through the adhesion of stem cells to the forming bone callus before the formation of bone regenerate. To prevent the development of postoperative pathological conditions caused by hypercoagulable syndrome, therapeutic strategies are used to use anticoagulants (heparin, warfarin). However, their use limits the normal formation of a fibrin clot in vivo. This can slow down the migration of mesenchymal stem cells (MSC) and disrupt the formation of callus, inhibiting the processes of osseointegration of the implant and bone healing. The study’s goal was to study the effect of heparin in a gradient of low and high concentrations on the migration activity and stem capacity of human MSCs under in vitro cultivation conditions. According to the results of flow cytometry, it was revealed that high concentrations of heparin (130, 260 IU/ml) in a 2D cultivation model contribute to an increase in the number of cells expressing surface markers CD73 and CD90, which indicates that MSCs retain high clonogenic potential. A 3D model of in vitro cultivation with the addition of heparin and osteosubstituting implants bearing a CF coating with a roughness index of Ra = 2.6-4.9 μm contributed to preserving the “stemness” character of MSCs through the expression of surface markers CD73 and CD90. According to the results obtained using the xCELLigence system, heparin at a later time (from 20-40 hours) increases the invasion of MSCs through micropores that simulate the state of the blood vessel walls. However, in the presence of HAP nanoparticles that mimic the remodeling processes of the mineral bone matrix and/or resorption of bone cement, the effect of heparin was less pronounced. The results can be used in the field of regenerative medicine associated with the introduction of MSCs. The data can serve as a prerequisite for developing new therapeutic strategies for surgical patients with a high risk of postoperative thrombosis after osteosynthesis. 

The development and progression of heart failure is associated with a variety of pathophysiological mechanisms, of particular interest is the study of the inflammatory response as a fundamental link in the pathogenesis of CHF and its main component – decompensation. An open, non-randomized, prospective study was carried out to evaluate the clinical and morphological features of subclinical inflammation in patients with acute decompensation of ischemic chronic heart failure with a reduced ejection fraction. The study included 25 patients with decompensated ischemic CHF with left ventricular ejection fraction < 40% aged 35 to 75 years (60.12±9.3 y. o.). In this study the dynamics of the serum content of C-reactive protein (CRP), N-terminal fragment of the brain natriuretic peptide precursor protein (NT-proBNP), soluble ST2(sST2), insulin-like growth factor-1 receptor (IGF-1R), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNFα) was performed by multiplex immunoassay using the FLEXMAP 3D. All studied patients were divided into two groups depending on the diagnosed myocarditis: patients with no signs of myocarditis and patients with myocarditis. It was found that in the group of patients with diagnosed myocarditis there was an increased content of CRP, IGF-1R, IL-6 and IL-10, TNFα compared to the group of patients without myocarditis. The median concentrations of the NT-proBNP and sST2 in both groups did not differ. At the follow-up visit a year later, there was a decrease in the content of CRP, NT-proBNP, IL-6 in both groups. In the group of patients with myocarditis, an increase in the content of sST2, IGF-1R, IL-10 was observed. Thus, the study carried out in dynamics revealed significant differences in the degree of changes in the serum activity of pro- and anti-inflammatory cytokines and biomarkers of cardiovascular risk in patients with decompensated heart failure with systolic dysfunction with diagnosed myocarditis and in its absence. 

Preeclampsia (PE) is one of the most common complications of pregnancy, and it can be after 20 weeks of gestation. It ends only with a complete dissection of afterbirth. Traditionally, PE is subdivided into the early one, taking place through 34 weeks of pregnancy (EOPE) and the late one, which is after 34 weeks of gestation (LOPE). Clinical manifestations are similar in both cases however, risk factors and the severity of PE are different . It has been established that EOPE is determined by impaired trophoblast invasion and transformation of the spiral arteries of the uterus in early pregnancy, and late onset of PE is associated with oxidative stress of syncytiotrophoblast, which occurs secondarily, with limited gas exchange and insufficient intake of nutrients. Numerous studies have noted a significant contribution of immune responses to the pathogenesis of preeclampsia, however, the state of B-lymphocytes in EOPE and LOPE has not been studied. A comprehensive assessment of the condition of women with early (up to 34 weeks of pregnancy inclusive) and late (after 34 weeks) development of preeclampsia was carried out, taking into account clinical and anamnestic characteristics, the peculiarities of the formation of the structural components of the placenta, as well as determining the nature of differentiation and functional activity of B-lymphocytes. In peripheral venous blood, the content of CD19⁺, CD20⁺, CD19⁺CD27⁺IgD^±, CD19⁺CD20^- CD38⁺, CD20⁺CD5⁺-cells and serum levels of IL-5, IL-9, IL-13 were examined. Morphological examination included gross description, organometry, survey histology, and transmission electron microscopy. In the group of women with early preeclampsia in history, there were more often perinatal losses, premature births and medical abortions, and in the current pregnancy, intrauterine infection, oligohydramnios, placental insufficiency and fetal growth retardation. With late preeclampsia, metabolic syndrome, anemia, and a history of arterial hypertension were more often observed. In the peripheral blood of all women with preeclampsia, there was an increase in the content of CD20⁺CD5⁺-cells in comparison with those in uncomplicated pregnancy, more pronounced in the late onset of preeclampsia. Only in women with early preeclampsia blood levels of CD19⁺CD20^- CD38⁺ and CD19⁺CD27⁺IgD^±-cells, IL-5, IL-9 and IL-13 increased. Studies of the placenta in early preeclampsia indicated impaired implantation and pathological placentation with the development of primary placental insufficiency, which becomes chronic. In late preeclampsia, the development of placental insufficiency was determined by chronic disorders of maternal and fetal hemocirculation with increased deposition of fibrin and fibrinoid in the basal lamina and in the zones of villous epithelium necrosis. The study showed that the timing of the manifestation of preeclampsia is determined by the action of factors of the clinical history, structural rearrangements in the placenta and immune responses of B-lymphocytes are closely interrelated. 

The functioning of the secretory organs is closely related to the activity of the immune system. As is well known, this participation is manifested in the fact that at certain stages of activity, the lymphoid cells migrating to the organ can be involved in the regulation of secretion. In addition, the products of the immune system and even its cellular elements can become components of a number of secrets. Colostrum and milk contain a large number of cells of a wide spectrum (up to 1/3 of the volume), of which the number of lymphocytes is up to 16% of leukocytes. Lymphocytes, in an immunologically active form, entering the newborn’s body with colostrum, activate the cellular immunity system. The transport of lymphokinin mediators plays a certain role in this process. Microphages, T- and B-lymphocytes, penetrating through the intercellular spaces into the lymphoid layer of the intestine, transmit immunoreceptors to the prolymphocytes of the newborn, "armed" with their activity to recognize genetically foreign ones. The lymphocytes contained in colostrum are the cells of the immune system that provide cellular and humoral immunity. They are mainly represented by T-cells, B-cells and killer cells. Milk T-cells produce a full spectrum of immune regulatory proteins such as interferon, tumor necrosis factor alpha. These cells are the cells of the immune memory. Newborns who received the first portion of colostrum no later than an hour after birth are characterized by an increased number of leukocytes, more pronounced phagocytosis, which indicates the stimulation of hemo- and lymphocytosis. When carrying out transmission and scanning electron microscopy in the epithelial layer of the intestine, cellular elements were found that got there from the intestinal lumen. Microsections show how cells of a lymphoid nature, pushing apart the structures of the epithelial layer, bypass natural barriers and, at the same time, retain their physiological usefulness. The possibility of penetration of immunocompetent cells of the mother’s colostrum into the bloodstream of the young is proved using the natural label of the female’s cells – sex chromatin. Naturally, sex chromatin-labeled cells were sought in male newborns. The detection of colostrum cells in the intestinal wall and bloodstream of the young is approximately 25% in the blood, 1% in the lymph, and about 70% in the intestine. There is no doubt that the leukocytes of colostrum are of exceptional importance in creating immunity in newborn animals. 

Currently, the existence of a wide range of subpopulations of CD8⁺T-lymphocytes has been revealed, among which there are subpopulations of naive and effector cells, as well as memory cells. CD8⁺T-lymphocytes are thought to be a population of lymphocytes with high cytotoxic activity, which is of extreme importance during pregnancy. Given that each subpopulation is characterized by a set of produced mediators, surface and intracellular markers, we can assume their role in the pathogenesis of preterm birth. This determined the need to investigate the role of naive cells, effector cells, and memory cells in the development of spontaneous preterm birth. Data on the content of naive CD8⁺-lymphocytes in the peripheral blood of women with threatened preterm birth are practically absent. It was found that the infiltration of CD8⁺-lymphocytes in the area of uteroplacental contact was associated with the development of timely delivery. Chronic chorioamnionitis is the most common condition in idiopathic preterm birth and is characterized by the infiltration of maternal CD8⁺Tcells into the chorioamniotic membranes. Currently, it is believed that chronic inflammatory lesions of the placenta represent maternal antifetal rejection. This led to the study of the role of these cells in the pathogenesis of preterm birth. Purpose. To establish a possible pathogenetic mechanism of preterm birth in women with threatened preterm birth on the basis of the revealed features of differentiation and functional activity of CD8⁺- lymphocytes at the systemic level

Materials and methods. The survey of women was carried out on the basis of the Federal State Budgetary Institution “V. Gorodkov Ivanovo Research Institute of Maternity and Childhood” of the Ministry of Health of the Russian Federation. A total of 126 women were examined, which were retrospectively divided into 2 main groups – women with threatened preterm birth(n = 68), which was divided into 2 subgroups – with the outcome of pregnancy preterm birth (n = 30) and timely delivery (n = 38). The control group included 58 women with uncomplicated pregnancy and who gave birth on time. In the CD8⁺-lymphocyte population, the content of central – Tcm (CD45RACD62L⁺), preterminally differentiated-Tem (CD45RACD62L^- ) and terminally differentiated-Temra (CD45RA⁺CD62L^- ) memory cells was determined. In all memory cell populations, the content of cells producing Granzyme B intracellularly was determined. The studies were performed using monoclonal antibodies (mAT) by flow cytometry on a FACSCanto II cytometer using the FACSDiva software (Becton Dickinson, USA).

The analysis of the features of the relative content of CD8⁺-lymphocytes in the main group of women, depending on the outcome of pregnancy, was carried out. When comparing patients with a clinic of threatened preterm birth, whose pregnancy ended prematurely, a higher content of CD8⁺-lymphocytes was revealed than in group c of women who gave birth in a timely manner, which indicates a high stimulation of cytotoxic T-lymphocytes in this group of women. With threatening preterm birth, there is an increase in the content of naive CD8+-lymphocytes in the peripheral blood. Data on the content of naive CD8⁺-lymphocytes in the peripheral blood of women with threatened preterm birth are practically absent. The increase in CD8⁺Tn levels is more pronounced in the subgroup of women with a favorable pregnancy outcome. Given this fact, it can be assumed that in women with preterm birth, a lower CD8⁺Tn is associated with their increased differentiation into effector T-lymphocytes with their subsequent migration to the placental zone. This process could determine the observed decrease in the level of terminally differentiated granzyme-producing CD8⁺-lymphocytes in a subgroup of women with a pregnancy outcome of preterm birth, which coincided with the literature data. 

During the course of chronic viral infections or tumor growth, due to the constant presence of antigen and inflammation, a dysfunctional state of T-cells called exhaustion occurs. Factors associated with T-cell exhaustion include an increase in the expression of various inhibitory receptors, also known as checkpoint molecules, which leads to inhibition of the proliferation and production of mediators such as IL-2, IFNγ, and TNFα.

The TIM-3 molecule is expressed on a variety of immune cells, including dendritic cells, macrophages, and T-cells, and mediates suppressive activity on immune cells. Sustained expression of the PD-1 receptor on T-lymphocytes is also associated with the exhaustion phenotype, while it remains unclear how the expression of these inhibitory receptors normally differs from that in pathological conditions of the body, which are characterized by an increase in the number of exhausted T-cells.

The aim of the study was to determine the relative and absolute number of T-cells expressing PD-1 and TIM-3, as well as the number of PD-1 and TIM-3 molecules on the surface of CD4⁺ and CD8⁺T-cells in healthy donors and breast cancer (BC) patients. Group of BC patients were conditionally divided into two groups depending on the degree of disease progression into patients with primary (without metastases) and metastatic BC.

As a result of the study, it was shown that an increase in the absolute number of PD-1⁺CD4⁺T-cells is observed in breast cancer patients. The absolute number of molecules per cell is also higher in BC patients compared to healthy donors. For patients, a tendency towards an increase in the absolute number of TIM-3⁺CD4⁺T-cells was shown in comparison with healthy donors and in a row from primary disease to metastatic BC.

Thus, differences in the expression pattern of TIM-3 and PD-1 checkpoint molecules are observed when comparing the norm and malignant pathology of the breast, and can become an important marker of the functional state of T-lymphocytes in BC patients. 

Exposure to alcohol causes imbalances in neuroimmune function and impaired brain development. Alcohol activates the innate immune signaling pathways in the brain. Neuroimmune molecules expressed and secreted by glial cells of the brain (microglia, oligodendroglia) alter the function of neurons and further stimulate the development of alcoholic behavior. Various signaling pathways and brain cells are involved in the transmission of neuroimmune signals. Glial cells are the main sources of immune mediators in the brain, which respond to and release immune signals in the central nervous system. The aim of this study was to study neuronal elements: morphometric parameters of glioblasts, synaptic structures and properties of synaptosomal GABAA-benzodiazepine receptors of the neuroimmune system in the embryogenesis of the human brain under perinatal exposure to alcohol. Changes in glioblasts in the brain tissue of human embryos and fetuses were revealed under conditions of chronic prenatal alcoholization with an increase in gestational age compared with control subgroups: a significant increase in the average number of glioblasts, the length of the perimeters of presynaptic terminal structures, postsynaptic density, presynaptic terminal regions were significantly less (p < 0.01) in the study group than in the control comparison group. Exposure to ethanol leads to a decrease in the affinity of GABAA-benzodiazepine receptors, which affects neuronal plasticity associated with the development and differentiation of progenitor cells (glioblasts and neuroblasts) during embryogenesis of the human brain and leads to suppression of GABAergic function in the brain. This causes a disruption in the interconnection of embryonic cells in the brain, leads to excessive apoptosis due to the activation of glial cells of the nervous tissue, disruption of neuroimmune function in the developing brain, changes in neuronal circuits, as well as a change in the balance of excitatory and inhibitory effects, which affects the functional activity in the central nervous system. Glial activation is a compensatory reaction caused by neuroplastic changes aimed at adapting the developing brain of the embryo and fetus under conditions of neurotoxicity and hypoxia under the influence of prenatal alcoholization of the maternal organism and the effect of ethanol on the fetus. The dynamics of changes in glial elements and receptor activity in the nervous tissue of human embryos and fetuses under conditions of prenatal exposure to alcohol indicates a more pronounced effect of alcohol on the earliest stages of human embryo development, which is of great practical importance in planning pregnancy and the inadmissibility of alcoholization of the mother in order to avoid negative consequences in offspring. 

In obese patients, the relationship between the content of chemerin in blood plasma and the expression of genes TFAM, Drp1, MFN2, SOD, BAX, responsible for quality control of mitochondria, in insulin-dependent tissues (adipose tissue, liver) was revealed. The tissue-specific features of gene expression (TFAM, Drp1, MFN2, SOD, BAX), the number of mtDNA copies in the studied depots in obese patients were established. It has been proven that a change (decrease) in the number of mtDNA copies in insulin-dependent tissues can have a protective effect on mitochondria under conditions of increased oxidative stress. It was found that in patients without type 2 diabetes, an increase in chemerin production promotes the activation of the antioxidant system in the visceral adipose tissue but not in the liver. On the contrary, all obese patients with type 2 diabetes showed a decrease (compared with patients without type 2 diabetes) in the plasma level of chemerin. Thus, the low content of chemerin in the blood plasma in patients with type 2 diabetes mediates the formation of mitochondrial dysfunction in insulin-dependent tissues (adipose tissue, liver). 

The study of the bronchial asthma pathogenesis is an urgent problem due to its high prevalence and often developing uncontrolled severe ashma, including in childhood. The first signs of asthma development tend to occur in childhood, which causes deterioration in the patient’s quality of life and early disability. Since BA is a genetically mediated process, the severity of the disease is assumed to depend on the presence of a specific allelic variant in the mediator (e.g. cytokines) genes involved in the BA pathogenesis. The aim of this study was to search for immunogenetic markers of severe asthma in Slavs children living in Krasnoyarsk city. The quantitative indicators of the Th1/Th2/Th17-cytokine profile in children with bronchial asthma (BA) with varying disease severity, depending on the polymorphism of cytokine genes, using the method of multiplex analysis (xMAP), were first determined. Changes in the cytokine background in BA patients fit into the concept that a percentage of neutrophilic endotype, which performs its functions through Th1 and Th17-lymphocytes in severe asthma, increases. In addition, the cytokine profile data depending on concomitant acute respiratory infections were obtained. There was an imbalance when analyzing the cytokine plasma level, with a tendency to maintain the protective functions of the immune system among patients in remission. Distribution of cytokine genes was obtained: allelic variants of IL12B rs321220*G, IL13 rs1800925*C, IL31 rs7977932*C and IL33 rs7044343*T are the most common in the population sampling from Krasnoyarsk. The probability of the genotype association of cytokine genes (IL12B, IL13, IL31, IL33) with the state of the immune system in bronchial asthma with varying disease severity in children was studied: a significant association of the TT genotype IL12B rs3212220 with a low concentration of IL-12B was presented. Our data obtained can be used along with the previously obtained immunogenetic markers of severe and uncontrolled asthma in children for patient-specific prognosis of the disease nature. 

Long-term complications of type 1 diabetes mellitus (T1DM) in children and adolescents are an important problem in modern medicine. Recently, the role of immune mechanisms, in particular, chronic inflammation, in the development of both T1DM and its microvascular complications has been actively discussed. Activation of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) leads to hyperproduction of proinflammatory cytokines, chemokines, adhesion molecules involved in the formation of diabetic microvascular complications. At the same time, TLR2 and TLR4 gene polymorphism alters the immune susceptibility to the endogenous ligands, which may increase the risk of diabetic microangiopathies. The aim of this study is to evaluate the frequency of genotypes and alleles of TLR2 and TLR4 genes distribution and to determine the content of TNFα, IL-1, VCAM-1, fractalkine, endothelin-1 in adolescents with T1DM with microvascular complications. We examined 139 adolescents with T1DM from 14 to 18 years old and 56 healthy teenagers. Patients with T1DM were divided into two groups: Group I – patients with poor glycemic control (HbA1C > 9.0%), (n = 64); Group II – patients with satisfactory glycemic control of T1DM (HbA1C ≤ 9.0%), (n = 75), including adolescents with optimal (HbA1C < 7.5%) and suboptimal glycemic control (7.5% ≤ HbA1C ≤ 9.0%) (ISPAD clinical practice consensus guidelines 2014). According to the presence of microvascular complications, the groups were subdivided into subgroups: Iа (n = 49), IIа (n = 38) – adolescents with verified microvascular disorders: diabetic retinopathy, nephropathy and neuropathy; Ib (n = 15), IIb (n = 37) – without microvascular complications. Allelic variants of TLR genes were determined using test systems GosNII genetics (Moscow). The content of cytokines in blood serum was carried out by the method of enzyme-linked immunosorbent assay “BIOSCIENCE”. Data were analyzed using software packages Statistica version 6.0. The assessment of TLR2 (Arg753Gln) and TLR4 (Thr399Ile) polymorphism distribution did not reveal significant differences between the observed subgroups and the control. In Ia and IIa subgroups (with complications) Asp299Gly variant was noted to be significantly less common when compared to subgroups Ib, IIb and controls. The presence of Gly allele in TLR4 gene was found to disrupt the expression of TNFα and VCAM-1 and can be considered protective for the development of microvascular complications. 

A pleiotropic cytokine TNFα is an important inflammatory mediator of a number of diseases; its biological functions are fulfilled through two different receptors, TNFR1 and TNFR2. Changes in the ratio between these types of receptors shifting the balance between the pro-apoptotic and proliferation signaling pathways play a crucial role in eliciting the cell response to TNFα. The pathological processes in the body can alter the levels of TNFR1 and TNFR2 expression on the cells involved in disease development. Therefore, this study was aimed at investigating the level of co-expression of type 1 and 2 TNFα receptors in the major subpopulations of peripheral blood cells in patients with rheumatoid arthritis (RA) and bronchial asthma (BA). The greatest changes in the percentage of cells expressing TNFR1 and TNFR2 were revealed for the B-lymphocyte subpopulation. For the T-lymphocyte subpopulation, there were some differences in the percentage of cells expressing exclusively TNFR1 in RA and BA patients compared with those in healthy subjects, as well as between the RA and BA groups. A higher percentage of double-negative monocytes was observed in patients with BA and RA compared to healthy subjects. These findings indicate that the coexpression profile of TNFR1 and TNFR2 receptors in patients with RA and BA differ within these groups as well as compared to that in healthy subjects. These immune cell populations are actively involved in the pathogenesis of both rheumatoid arthritis and bronchial asthma, so the results may indicate that these cells might show different responses to TNFα as the percentage and the number of receptors on their surface vary. 

In this article, a retrospective analysis of the medical histories was carried out in order to develop an individualized approach to treating COVID-19. Questions were raised about the advisability of the universal immunosuppressive therapy, the need to prescribe glucocorticosteroids only taking into account the cytokine profile of patients, the relationship of glucocorticosteroid therapy and carbohydrate metabolism disorders, as one of the most common complications of pharmacotherapy COVID-19 in the patients we studied. Unjustified immunosuppression in the stage of active fight against the infectious agent as a factor of chronization of the process and decrease of the body reactivity, as well as neutralization by immunosuppressive therapy of factors of protection of innate non-specific immunity mobilized to fight the causative agent. The importance of taking into account the probability of thrombosis with consideration of coagulogram indices and thrombosis markers (D-dimer, fibrin degradation products) does not exclude the risk of the hemorrhagic complications when prescribing high doses of anticoagulants. Antibacterial therapy for uncomplicated viral infections is neither an etiologic nor a pathogenetic treatment option. In addition, it leads to the emergence of resistant strains of microorganisms as a result of mutational variability and evolutionary adaptations of bacteria, which greatly complicates the choice of an effective antibacterial drug in some cases. Antithrombotic, glucocorticosteroid and antibacterial therapy should be clinically and laboratory justified in each individual case. The article focuses on the safety of prescribing antipodagric agents in the treatment of COVID-19 as anti-inflammatory. The review considers all the above-mentioned aspects of COVID-19 therapy with reference to foreign studies, describes options for the pathophysiological development of infection. We note the need to develop systematic data on coronavirus, changes that the pathogen induces in the body. This will allow the development of innovative and effective therapeutic strategies for the treatment of the new coronavirus infection. 

It is known that the combined use of vaccines, cytokines and various immunomodulatory drugs contributes to the development of a full-fledged immune response. This approach makes it possible to enhance the immunogenicity of modern vaccines and to direct the development of immune responses according to the humoral or cellular type, depending on the properties of the pathogen of a particular disease. The improvement of preventive drugs due to their combined use with cytokines and immunomodulators increases the intensity of immunity, increases the level of production of specific immunoglobulins, the protectivity of antigens, and also reduces the manifestation of adverse reactions leading to post-vaccination complications.

Immunomodulators are already successfully used in drugs intended for the treatment and prevention of chronic herpes infections and influenza vaccines. Numerous experimental and clinical data indicate a positive effect of the use of immunomodulatory drugs in the vaccination of various viral and bacterial infections, including particularly dangerous ones.

Improving the specific prevention of cholera can be achieved through immunomodulatory agents that can stimulate the formation of a local and systemic immune response.

We conducted a comparative assessment of the feasibility of the combined use of the cholera bivalent chemical vaccine (the Federal Government Health Institution Antiplague Research Institute “Microbe”) and immunomodulators in order to increase the effectiveness of cholera vaccination.

Since the cholera vaccine causes the activation of the humoral immune response, the production of specific immunoglobulins in the body of vaccinated experimental animals and the effect of immunomodulators on this process at different times of the post-vaccination period were evaluated.

The ability of immunomodulators to increase the protective activity of the cholera vaccine was studied by infecting animals with a virulent strain of cholera one month and seven months after vaccination.

It was found that immunomodulators increase the immunogenicity and protectivity of antigens that are part of the anti-cholera vaccine. The use of all immunopreparations increases the production of specific immunoglobulins in the serum of vaccinated experimental animals. It was shown that in the first month after vaccination, polyoxidonium most effectively stimulated the formation of antibodies, but lycopide contributed to a longer retention of anti-cholera immunoglobulins in the serum of vaccinated rabbits. The combined use of the vaccine and lycopide prevented the development of cholera in all animals taken in the experiment, including those vaccinated with a reduced dose. In the long-term post-vaccination period, this immunomodulator increased the protectiveness of the anti-cholera vaccine by three times. Polyoxidonium and derinate also increased the protective effect of the cholera vaccine, but were slightly inferior to lycopide. The combined use of cholera vaccine and immunomodulators, especially lycopide, can be used to improve specific cholera prevention.

Allergic rhinitis and bronchial asthma are widespread respiratory allergic diseases. In some territories of the Russian Federation, the dominant cause of pollinosis is ragweed. The aim of the study was to evaluate the clinical and immunological efficacy of ASIT with the allergen Ambrosia artemisiifolia in patients sensitized to Ambrosia trifida in the Samara region. Patients with proven sensitization to Ambrosia trifida was held immunotherapy with Ambrosia artemisiifolia allergoid preseason. After treatment, patients had a decrease in the severity of symptoms of allergic rhinitis according to VAS (p = 0.00001), a decrease in the need for medications (p = 0.0003), as well as the need for corticosteroids against the background of therapy from 34.6% to 0% (p = 0.00001). In 8% of cases, the result of treatment was good, in 69% satisfactory, in 23% unsatisfactory. In the control group, there were no changes in the severity of symptoms (p = 0.858). Also, in the control group, the need for medications remained unchanged and 14.3% of patients continued to use corticosteroids.

After ASIT, there was a decrease in the level of IL-4 (p = 0.002), and a decrease in the ratio of IL-4/ IL-10 (p = 0.0063); at the same time, changes in the level of other cytokines (IL-10; IFNγ) were statistically insignificant (p > 0.05). Before treatment, the levels of IL-4/ IL-10 in both groups were comparable, and after treatment, the differences became statistically significant (p = 0.031). We did not get a statistically significant change in the level of IgG4 Amb a 1 or IgG4 Amb trifida. There was no correlation between the level of individual cytokines and the results of treatment. As a result of the conducted ASIT, positive clinical and immunological results were obtained. In most patients, the disease has acquired a controlled course. At the same time, the lack of excellent and low number of good results of ASIT is probably due to the intraspecific allergenic properties of ragweed. 

The study aimed to compare the effectiveness of various pharmacotherapy regimens for infertility of tubo-peritoneal genesis. Under constant supervision were 96 patients referred to the hospital for diagnostic laparoscopy for infertility of tubo-peritoneal genesis, divided equally into 4 groups depending on the pharmacological treatment methods: the 1st group received basic pharmacotherapy (BPT) after endoscopic surgery (antibacterial, antifungal, vitamin therapy). Patients of groups 2-4, in addition to BPT, received Hepon, Cycloferon or Lavomax, respectively. The control group consisted of 38 gynecologically healthy women. Laboratory examination was performed within 24 hours after the operation and on the 30th day after BPT. Vaginocervical lavage and plasma were assayed for the activity of lipid peroxidation processes, the state of the antioxidant system, the level of stable nitric oxide metabolites, neopterin, C-reactive protein, cytokines (TNFα, IL-1β, IL-8, IFNγ, IL-18, G-CSF, IL-4, IL-10), immunoglobulins (IgM, IgG, IgA, sIgA), components of the complement system (C3, C4, C5, C5А), phagocytic and oxygen-dependent activity of polymorphonuclear leukocytes. It was established that the use of immunomodulatory and antiviral activity medication with BPT according to the degree of increasing efficiency in the correction of immunometabolic laboratory parameters at the systemic and local level in infertility of tuboperitoneal genesis is as the following sequence: basic pharmacotherapy < basic pharmacotherapy + Hepon < basic pharmacotherapy + Cycloferon < basic pharmacotherapy + Lavomax. 

Postpericardiotomy syndrome (PCTS) is one of the most frequent cardiac surgery complications seen in 9-65% of patients. Despite its widespread occurrence, the mechanisms of the development of PCTS are still understudied. drug. The use of colchicine in cardiac surgery patients is of particular interest. Due to the ability of this drug the colchicine mechanisms of action are able to inhibit the mobilization of the NLRP3 inflammasome assembly, to suppress the activation of caspase-1. As a result, it can prevent the release of proinflammatory cytokines, namely IL-1β and IL-18. There are conflicting data on the effect of colchicine on the PCTS progression within the systemic inflammatory response after cardiac surgery. In this regard, it was important to study the dynamics of serum levels of IL-6, IL-10, IL-1β, and TNFα in patients before coronary artery bypass grafting (T1), 6 hours (T2), and 10 days (T3) after surgery, and to evaluate the effect of colchicine on the development of PCTS. The results of our research showed a significant increase of IL-10 in both groups 6 hours after surgery. However, on the 10th day, the increase in the level of IL-10, compared with the initial values, was higher in the 1^st group – 2 times, compared with the 2nd group. In both groups, showed significant increase in serum concentration of IL-6 after 6 h surgery, with a subsequent decrease in the expression at the stage of T3, while the IL-6 levels in the 2^nd group was statistically notably higher than T1. The incidence of pleurisy was lower in the group of patients taking colchicine. Only in the 1st group IL-6 levels were directly associated with IL-10. In patients with pleurisy, the level of released IL-10 and TNFα was significantly higher in the 2nd group. There were no significant intergroup differences in serum levels of IL-1β and TNFα, as well as significant changes in IL-1β between the stages of observation. Analysis of TNFα expression revealed significant differences in TNFα content in the 1^st group between the T1-T3 and T2-T3 stages. In both groups, multiple positive associations were found between the studied indicators. Thus, data were obtained indicating the antiinflammatory effect of colchicine in cardiac surgery patients. This was clinically expressed in a tendency to a lower incidence of pleurisy, and was accompanied by increased expression of IL-10, which has an antiinflammatory and immunomodulatory effect against the background of the drug in the postoperative period. 

The aim of the study was to study the effectiveness of the use of immunomodulators and antioxidants in the correction of immune status parameters in patients with adenomyosis. 70 patients were examined, including 57 women (the main group), who were diagnosed with adenomyosis according to the results of a comprehensive clinical, ultrasound and hysteroscopic examination. The control group consisted of 23 gynecologically healthy women. After verification of the diagnosis, all patients with hypertension received standard treatment (SL) (clinical recommendations of the Ministry of Health of the Russian Federation from 2016). Among the female patients, 19 women received only SL (1^st subgroup). 38 exhaust gases examined, in addition to SL, received various combinations of antioxidant, immunomodulator, and membrane protector and were divided into two subgroups. The second subgroup included 20 patients in addition to the SL receiving sodium ribonucleate; Hypoxene and phospholipids. The third subgroup included 18 patients who additionally received Inosine + Nicotinamide + Riboflavin + Succinic acid; Meglumine acridone acetate, and glycyrrhizic acid + phospholipids. The analysis of the cytokine status and the compliment system was performed at the time of admission and by the 15^th day of observation. Detected changes of the cytokine status, complement system activation, increased oxygen-dependent activity of neutrophils in the peripheral blood (increased production of active oxygen forms as a result of respiratory burst) confirm the presence of immune inflammation on the systemic level. Insufficient clinical-laboratory efficacy of ST in the correction of immune changes has justified the use of drugs with immunomodulating, antioxidant, and membrane protective properties in the pharmacological therapy of adenomyosis, which have been successfully used in the treatment of other diseases with similar disorders.Optimal combinations of immunomodulators and antioxidants in the correction of the immune status of patients with adenomyosis were revealed. The study performed demonstrates the efficacy of correcting immune status parameters in patients with adenomyosis when the standard treatment is combined with antioxidant and immunomodulating agents. 

Purpose: to study the changes in quantitative values and functional activity of immunocompetent cells on application of glucoseminylmuramildipeptide in children with allergen-induced phenotype of bronchial asthma.

We have performed an integrated assessment of parameters of innate and acquired immunity in 60 children at the age of 3-11 years old with allergen-induced bronchial asthma (BA) with mild clinical course of disease, and in 30 healthy children of the same age. BA phenotypes were verified in accordance with PRACTALL international consensus report (2008). Study exclusion criteria were: severe course of bronchial asthma and application of immunocorrecting therapy during preceding six months. We conducted a prospective parallel open study of the effect of glucoseminylmuramildipeptide on the parameters of immunocompetent cells during three months with division into two control groups by random sampling technique on the basis of therapy being performed. To analyze the venous blood cells, we used flow cytofluorometer COULTER EPICS XL by Beckman Coulter Inc. Cytokine levels were determined using immunoenzyme method with reagents by R&D Diagnostics Inc (USA) and IgE – with reagents by Alkor Bio Company (St. Petersburg), production of cytokines – using reagents by Vektor-Best (Novosibirsk). Statistical processing of data was performed using Statistica 10 program with significance level p < 0.05, assessment of correlations by Spearman correlation analysis, multidimensional correlation analysis with V.P. Terentyev’s method of correlation pleiades (1959) and testing for normal distribution of characteristic values (Shapiro–Wilk). The scope of our study permitted to evaluate its findings with accuracy 95-99%.

The changes of the adaptive response system in children with allergen-induced phenotype of BA were characterized by the intensified proliferation, suppression of negative regulation processes, activation of synthesis of Th2-profile cytokines, and intensified synthesis of IgE.

The identified impairments of availability, functional activity of immunocompetent cells and cytokine production were preserved in application of inhaled corticosteroids therapy, with further decreasing of IFNγ synthesis.

Application of glucoseminylmuramildipeptide in children with BA provided for reduction of spontaneous and mitogen-induced production of IL-4 and correction of deviated structural and functional characteristics of immunocompetent cells.

Incorporation of glucoseminylmuramildipeptide into therapeutic regimens for allergen-induced phenotype of BA in children promoted normalization of parameters of the cellular component of immune system, amelioration of Th1/Th2-imbalance, increase of Th1 activity, and adequate spontaneous and induced production of IFNγ by peripheral blood cells. 

The study aimed to develop a personalized pharmacological correction of immune, metabolic and neuropsychiatric disorders in chronic cerebral ischemia (CCI) stages I and II. The study included 104 patients, of which 76 were female and 28 were male, with CCI on the background of grade II hypertension, of which 52 patients were with stage I and 52 with stage II at the age of 50±5 years. Clinical and laboratory parameters were studied in 22 healthy donors of the same age who formed a control group. Patients with CCI were randomized according to gender, age, treatment method, concomitant pathology, and duration of the disease. Evaluation of clinical and laboratory data was carried out at the beginning of treatment and 2 weeks after its end. The sorption capacity of erythrocytes and the sorption capacity of the glycocalyx (SEG), the activity of lipid peroxidation processes, the state of the antioxidant system were determined in blood plasma and erythrocytes, the level of stable metabolites of nitric oxide (SMNO), neopterin, C-reactive protein, cytokines (TNFα, IL-1β, IL-8, IFNγ, IL-18, G-CSF, IL-4, IL-10), immunoglobulins (IgM, IgG, IgA), complement system components (C3, C4, C5, C5A), phagocytic and oxygen-dependent activity of polymorphonuclear blood leukocytes. It has been established that for patients with CCI I with high concentrations of IL-8, IL-10, SMNO and a low SEG index, the intake of Cereton and Actovegin or Ceraxon and Mexicor will be insufficient for effective correction of immunometabolic disorders, which requires additional administration of an immunomodulator. Patients with CCI II, who have a higher plasma level of TNFα, IL-10 and low SEG values, need to prescribe Ceraxon, Mexicor and Glutoxim or Ceraxon, Mexicor and Polyoxidonium in order to obtain the maximum clinical and laboratory positive effect. 

The problem of treatment of oncological diseases is one of the most urgent for modern medicine. Existing treatment approaches are based on a surgical, radiation, chemotherapeutic approach, and the use of immunotherapy methods aimed at markers and / or specific antigens of tumors.

Approaches based on the mechanisms of cellular and molecular regulation of a specific antitumor immune response have shown their high efficiency (for example, antibodies against HER2 in breast cancer), but these approaches have a number of side and undesirable effects that limit their application. Considering the central role of the mechanisms of recognition of tumor antigens and their presentation to cytotoxic cells in effective tumor elimination, it is important to search for and develop approaches to restore these mechanisms in cancer pathology. Because maturation, differentiation of dendritic cells and their main function are impaired in oncological diseases, scientific research is underway to obtain mature dendritic cells and restore the natural way of antigen presentation to effector cells.

The work carried out limited clinical studies (13 patients with colorectal cancer), a previously developed protocol for obtaining antigen-primed dendritic cells of patients with colorectal cancer and their joint culture with autologous mononuclear cells in vitro. From the peripheral blood of cancer patients, dendritic cells primed with autologous tumor antigens (tumor cell lysate), which were co-cultured with their own mononuclear cells in the presence of immunoregulatory cytokines (IL-12 and IL-18). The resulting cell suspensions were purified from the culture medium and cytokines and used for a course of immunotherapy (weekly, 20-30 million cells intravenously, dropwise), consisting of 3-5 injections. At different periods of immunotherapy (before the start of the course of immunotherapy, 3 months and 6 months after the end of immunotherapy), immunological parameters were assessed in the peripheral blood of patients (immunogram (CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD19, CD16⁺CD56⁺-cells), the relative content of T-regulatory cells (CD4⁺CD25⁺FoxP3⁺-cells), myeloid suppressor cells (CD14⁺HLA^-DR^- cells)) and assessed the cytotoxic activity of peripheral blood mononuclear cells of patients against cells of the tumor line of human colorectal cancer (Colo-320).

The data obtained showed that in cancer patients, against the background of ongoing immunotherapy, the indicator of the direct cytotoxic test significantly increases, which makes it possible to judge the effective stimulation of the antitumor cellular immune response. This is also indicated by an increase in the relative number of CD16+CD56+-cells (NK-cells) 3 months after immunotherapy. The study of immunosuppressive cells in the blood of cancer patients showed the absence of significant changes in CD14⁺HLA^-DR^- -cells and T-regulatory cells.

Thus, limited clinical studies of immunotherapy of patients with colorectal cancer based on autologous dendritic cells primed with lysate of autologous tumor cells demonstrated an increase in the antitumor cytotoxic immune response. 

Psoriasis is a chronic autoimmune disease in which the skin and joints are involved in the pathological process. It was found that the recurrence of rashes in this disease occurs due to the resident memory cells of the skin. The number of CD4+CCR3+ effector memory cells in peripheral blood correlates with the severity of the disease. Therefore, the aim of our work is to study the phenotype of peripheral blood memory cells in patients with psoriasis.

The study included 6 healthy donors: average age – 45.4 (min – 29, max – 55), women – 3, men – 3; 10 patients with psoriasis: women – 4, men – 6, average age – 37.3 (min – 23, max – 57), of which 5 patients with PASI > 10 and 5 patients with PASI < 10. The exclusion criteria for the study were the presence of autoimmune, oncological and hematological diseases, systemic therapy with immunosuppressive drugs for 1 month. Patients signed informed consent to participate in the study. Isolation of peripheral blood mononuclear cells was performed in a density gradient of ficoll-urographin (p = 1.082 g/L). Then cells were stained with fluorochrome-conjugated monoclonal antibodies to surface markers of central (Tcm) and effector (Tem) CD4+ memory cells (CD4, CD45RO, CD197), the α-chain of the IL-7 receptor (CD127), and the γ-chain of the IL-7 receptor (CD132). Statistical analysis of the data obtained was performed using the Statistica 6.0 software package.

The percent of Tcm in the peripheral blood of donors was 33.4% (in – 18.2, max – 43.7), Tem – 28.7% (min – 13.6, max – 38.9), in patients with psoriasis: Tcm – 28.65% (min – 13.3, max – 59.6), Tem – 21.5% (min – 9.3, max – 38.6). In the peripheral blood of patients with psoriasis, among the central CD4+ memory cells, the proportion of CD127⁺CD132^- -cells is 26.00%, CD127⁺CD132⁺ – 1.69%, CD127⁺CD132^- – 69.00%, CD127^- CD132⁺ – 1.94%. Among effector CD4⁺ memory cells, the proportion of CD127⁺CD132^- -cells is 23.58%, CD127⁺CD132⁺ – 1.18%, CD127⁺CD132^- – 69.84%, CD127^- CD132⁺ – 0.70%. A direct correlation was found between the number of CD127^- CD132⁺ central memory cells and the PASI value (r = 0.639, p < 0.05).

In patients with psoriasis, the proportion of central memory cells is higher than in healthy donors, while the number of effector memory cells is lower. A direct correlation was found between the number of central cells expressing the γ-chain of the IL-7 receptor and the severity of the disease. Activated memory cells are characterized by high expression of CD132. It can be assumed that this population of memory cells plays a role in maintaining autoimmune inflammation in patients with this disease, and also participates in the repopulation of skin resident memory cells. 

The steady increase in the number of autoimmune diseases and immune-mediated autoinflammatory processes causes an increased interest of doctors of all specialties in this topic and makes the issue of early detection of autoimmune disorders / autoimmune syndrome (AS) extremely urgent. These disorders often develop against the backdrop of an atypical stream of chronic active viral infections caused by persistent viruses, in particular those of the Herpesviridae family, and remain undiagnosed due to polysymptomatic disease, and various “clinical masks” of the disorders caused by them. The semi-quantitative method developed by us for screening assessment of the content of autoantibodies in the blood serum of patients suffering from ACAI caused by herpes viruses using the ELISA method (Immunodot) is a highly specific screening method that can allow for an objective assessment of the dynamics of the autoimmune process, as well as control the effectiveness of the ongoing complex antiviral and immunomodulatory therapy. The detection of autoantibodies of various specificity in the blood serum of patients suffering from an atypical chronic active infection caused by herpes viruses (ACAI) is an early diagnostic marker, necessary, first of all, to identify autoimmune pathology of the nervous system, which is associated with a long course of the active mixed herpes-viral process. 

The health of the newborn depends entirely on the state of the mother’s body throughout the pregnancy. Ensuring optimal conditions for keeping pregnant animals is based, first of all, on adequate feeding and ensuring the sanitary and hygienic conditions of the environment. The cow’s body undergoes a great load during the transition period, which begins 3 weeks before calving and lasts for six weeks. When the technology of feeding and housing is violated, during this period, metabolic disorders often occur in cows, which are manifested by increased production of ketones. It is known that the development of immunity in the early postnatal period in a calf largely depends on the timely feeding of colostrum. Maternal immunoglobulins from colostrum enter the systemic circulation of the newborn in the small intestine through the tubular system of epithelial cells by pinocytosis.

The aim of the study is to study the effect of subclinical ketosis in mothers cows on the formation of colostral immunity in calves born from them.

For the study, pregnant cows 3-6 years old were selected 3-7 days before delivery. Urine and blood samples were taken from the cows. In order to identify subclinical ketosis in cows, urine was tested for ketones. According to the results of the study, two groups of 10 animals were formed – in the first group (experimental) the level of ketone bodies in the urine ranged from 1.8 to 3.7 mmol/l, in the second group (control) ketones were not found in the urine. Immediately after calving, portions of colostrum were taken from the cows, and blood was taken from newborn calves a day after the first colostrum was fed. The content of immunoglobulins was studied in skim colostrum and in the blood serum of newborn calves. In the blood serum of day-old calves, the content of total protein was also determined by the biuret method, albumin – by the photometric method with bromcresol green.

According to the results of the study, a decrease in the classes of immunoglobulins G, M and A was found in the blood serum of cows before calving by 19.1-23.5%, in colostrum – by 23.7-34.4%, and in the blood serum of day old calves – by 21.7-27.6%. The decrease in IgM concentration was determined to the greatest extent. Subclinical ketosis of mothers had practically no effect on the content of albumin in the blood of calves. 

Genital mycoplasmosis in cows is a disease accompanied by a latent course, which complicates its timely diagnosis and the appointment of adequate therapy. The nonspecific symptomatology of mycoplasmosis, combined with periods of asymptomatic course, leads to the development of functional and morphological changes in the organs of the reproductive system of cows, resulting in infertility. Monitoring studies of livestock farms in the North-West region of the Russian Federation have shown that infection of the genitals of cows with mycoplasmas can be from 20 to 40% of the livestock. Moreover, there is a clear relationship between the high infection rate of the livestock and low reproduction rates. In this regard, livestock enterprises incur significant economic damage. One of the important mechanisms preventing the introduction of various pathogens into the reproductive tract is the resistance of the vaginal mucosa. Among these factors, the most important role is assigned to vaginal autoflora, epithelial desquamation, phagocytosis, acidity of vaginal secretions, the content of immunoglobulins, lysozyme and a number of other nonspecific protective factors in it. We studied the changes in the immuno-biological characteristics of vaginal secretions in the subclinical course of genital mycoplasmosis. Healthy cows with a negative PCR test for Mycoplasma spp. were selected for the study. and infected with Mycoplasma spp., without clinical signs of vaginitis. In both groups of animals, the concentration of hydrogen ions, the activity of lysozyme and immunoglobulins of the classes IgG, IgM, IgA and sIgA were determined in the vaginal secretions. Despite the fact that the persistence of mycoplasmas in the vagina is not accompanied by pronounced clinical signs of vaginitis, but the state of protective factors the mucous membrane undergoes significant changes. The conducted studies made it possible to establish that the long-term presence of mycoplasmas in the vagina of cows is manifested by a significant increase in the concentration of hydrogen ions by 41% and a decrease in the lysozyme activity of vaginal secretions by 2 times, that is, inhibition of the main factors preventing the colonization of mucous pathogenic microflora is observed. In addition, there is a redistribution of classes of immunoglobulins in the vaginal secretion. This is manifested by a significant increase in the content of IgM and sIgA against the background of a tendency towards a decrease in IgA. The noted changes in aggregate create favorable conditions for the introduction of secondary microflora and the development of bacterial-mycoplasma vaginitis, aggravating morpho-functional changes in the reproductive tract and increasing the risk of infertility.