Pregnancy depends on a delicate balance of immune activation and regulation

It is well recognized that immune tolerance is important to prevent semiallografted fetuses from rejection by maternal immunocompetent cells; however, immune activation also plays an important role in placental development and fetal growth. Basic and clinical studies have shown that an imbalance between immune activation and regulation can lead to implantation failure, miscarriage, and preeclampsia. Here, the balance between immunostimulation and immunoregulation in reproduction will be reviewed.

Primary immunodeficiencies with predominant impairment of antibody synthesis

The urgency of the problem of primary immunodeficiencies (PID) lies in the late diagnosis of this pathology due to the low awareness of doctors of various specialties, the formation of chronic diseases in patients, and high mortality in this group of patients. Currently, the concept of PID includes both traditional concepts - defects leading to the development of quantitative and / or functional insufficiency, and new concepts - uncontrolled activation of the proliferation of immunocompetent cells and the formation of autoimmune, auto-inflammatory and allergic diseases. The article discusses the diagnostic criteria for PID and the main directions in the treatment of this contingent of patients

Interrelation between Rheumatic Autoimmune Disease, Autohemolitic Anemia and Cancer Arising as Epiphenomenon on Paraneoplastic Syndrome

There are hemolytic anemias of different origin. For instance, these states may be induced by me­ans of so­­me exogenic hemolytic factors: by different organic and unorganic hemolytic toxins (phospho­rus, phe­nyl­hydrazin, saponins, arsenicum, lead and biotoxins – snake venom, mushroom poisons, mycotoxins, etc.), so­me medical preparations, radiations, some infectious agents and haevy burns. Besides, in some ca­ses, he­molytic anemias are induced by antibodies and immunocompetent cells against own tissues (auto­immune hemolytic anemia).

Estimation of the effect of lithium salts on cytokine production by blood cells in in vitro experiments

Aim. To study the effects of lithium salts on production of cytokines by immunocompetent cells in the whole-blood culture of patients with alcohol dependence and affective disorders.Materials and methods. The study materials were blood samples from 25 patients with alcohol dependence (AD) and 12 patients with bipolar disorder (BD). Blood diluted 1:1 with complete RPMI-1640 medium (Gibco, UK) was added to the wells of the culture plate, then new lithium salts (succinate, fumarate, pyruvate, ascorbate) and a reference salt – lithium carbonate at a final concentration of 1.2 mmol / l per lithium ion – were added. In parallel, control samples without lithium salts were tested; the samples were incubated for a day. The concentration of cytokines (interferon (IFN) γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, tumor necrosis factor (TNF) α) was determined in the culture supernatants on the MAGPIX multiplex analyzer (Luminex, USA) (Center for Collective Use “Medical Genomics”, Tomsk NRMC) using the Human Cytokine / Chemokine Magnetic Bead Panel (Merck, Germany).Results. All lithium salts had a unidirectional effect on the production of cytokines by immunocompetent cells (ICC), except for lithium ascorbate and IL-8. The concentrations of cytokines in the supernatants of loaded and control samples (spontaneous production) were comparable, which indicates an absence of stimulating or suppressing effects of salts on the functional activity of ICC under the experimental conditions. The effect of lithium ascorbate as an IL-8 inducer was detected: the production of IL-8 induced by lithium ascorbate was 2.3–2.5 times higher than its spontaneous production.Conclusion. The obtained results, as well as the previously revealed antioxidant and cytoprotective properties of new lithium salts, confirmed that they are promising for development of pharmacological agents with combined action.

Phototherapy of Brain Tumours Using a Fibre Optic Neurosystem

In this work, a new approach was tested to assess the cellular composition of tissues by time-resolved methods of fluorescence analysis of exogenous and endogenous fluorophores. First of all, the differences in fluorescence kinetics of endogenous fluorophores (coenzymes NADH and FAD) in tumour and immunocompetent cells were determined. After that, differences in fluorescence kinetics of photosensitizer 5 ALA-induced protoporphyrin IX were established due to its different metabolism in cells of different phenotypes. Kinetics of photoluminescence of NADH and FAD coenzymes as well as photosensitizer were studied by means of two different methods: time-resolved spectroscopy based on a streak-camera and fibre optic neuroscopy, which served to perform process monitoring and regular fluorescence diagnosis of the probed region. Time-resolved fluorescence microscopy (FLIM) was used as a control technique. Time-resolved spectroscopic fluorescence lifetime analysis was performed on sexually mature female rats induced with glioma C6 brain tumour under in vivo conditions; thus, under conditions where the immune system actively intervenes in the process of oncogenesis. In this regard, the aim of the study was to recognize the cellular composition of the brain tumour tissue, namely the ratio of cancer and immunocompetent cells and their mutual localization. Understanding the role of the immune system thus provides new ways and approaches for further diagnosis and therapy, making tumour-associated immune cells a prime target for modern therapies.

CHARACTERISTICS OF IMMUNOCOMPETENT CELLS IN CHILDREN WITH ALLERGEN-INDUCED PHENOTYPE OF BRONCHIAL ASTHMA TREATED WITH GLUCOSEMINYLMURAMILDIPEPTIDE

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.

Nonspecific Regulation of the Number of Immunocompetent Cells Under the Influence of DT Toxoid in Children With Glomerulonephritis

BackgroundStudies aimed at identifying the mechanisms of the immunoregulatory effect of vaccination with diphtheria and tetanus toxoid on the parameters of adaptive immunity in children with kidney pathology are limited. The study aimed to study the effect of revaccination against diphtheria and tetanus on the proliferation and differentiation of immunocompetent cells, the formation of specific antibodies, and the course of the disease in children with glomerulonephritis (GN).MethodsThe study included 45 children with glomerulonephritis (GN) aged 5 to 15 years, in remission from 6 months up to 4 years. Of these, 25 children were revaccinated with DT toxoid (Diphtheria-Tetanus toxoid with reduced antigenic content) and 20 were in the control group (not vaccinated). The frequency of development of local and systemic reactions and the course of GN were assessed. The subpopulation structure of lymphocytes was studied in dynamics after 1-6-12 months by flow cytometry and IgG levels to diphtheria and tetanus were studied by ELISA.ResultsIn 92% of children with GN, the post-vaccination period was uneventful. 8% showed a rise in temperature up to 37.3°C, without the development of local reactions. During the year, none of the patients had an exacerbation of GN or a concomitant disease. After revaccination with DT toxoid, a significant increase in IgG antibodies against diphtheria and tetanus was revealed, which persisted after 12 months - 7.5 [5.1-10.8] IU/mL (p &lt;0.001) and 7.2 [4.8-10.7] IU/mL (p &lt;0.001), respectively. In the post-vaccination period, a multidirectional change in the concentration of T-lymphocytes was noted: with an initially increased level, their percentage after revaccination with DT toxoid decreases from 83 (81-86) % to 78 (76-80)% after a month (p = 0.04) and up to 75 (69-79)% after 12 months (p&lt;0.001). In the control group, such a decrease was not observed. A similar picture was observed for T-helpers, cytotoxic T-lymphocytes, and in patients with an initially low percentage of cytotoxic T-lymphocytes, on the contrary, its increase was noted (p&lt;0.001), which is comparable with the value of this parameter in the group of children with initially normal value (H = 0.54, p = 0.76). The same patterns were observed in the change in the content of B-cells: one month after revaccination, the relative level of B-cells in patients with an initially lowered value increased (p = 0.02) and remained for 12 months (p&lt;0.001).ConclusionRevaccination with DT toxoid in children with GN not only does not cause undesirable changes in the system of immunocompetent cells but also has an immunomodulatory effect, which contributes to the favorable maintenance of the remission period of the disease.

Trained Immunity as an Adaptive Branch of Innate Immunity

The concept of trained immunity has become one of the most interesting and potentially commercially and clinically relevant ideas of current immunology. Trained immunity is realized by the epigenetic reprogramming of non-immunocompetent cells, primarily monocytes/macrophages and natural killer (NK) cells, and is less specific than adaptive immunity; therefore, it may cross-protect against other infectious agents. It remains possible, however, that some of the observed changes are simply caused by increased levels of immune reactions resulting from supplementation with immunomodulators, such as glucan. In addition, the question of whether we can talk about trained immunity in cells with a life span of only few days is still unresolved.

Effectiveness of treatment of patients with systemic autoimmune diseases on the background of reactivation of persistent Epstein-Barr virus infection

The article presents the study of effectiveness of inosine pranobex (IP) in patients with systemic autoimmune diseases (SAD) on the background of reactivation of persistent Epstein-Barr (EBV) infection. Among 380 patients with SAD (systemic lupus erythematosus, systemic vasculitides, rheumatoid arthritis, psoriasis), in 144 patients (37.9%) the reactivation of persistent EBV infection was detected through virus DNA identification using polymerase chain reaction (PCR) in three biological matrices (blood, saliva, scraping from the lesion site). 48 patients were receiving inosine pranobex at a dose of 50 mg/kg per day for three months. Treatment efficacy was controlled by studying the levels of expression of miR-146а, miR-155, miR EBV (BART-13 and BART-15), TLR9, the quantity of lymphocytes populations and subpopulations. After treatment, PCR results showed a decrease in viral replication in 66.7% of cases. The use of IP contributed to a significant decrease in the level of IgM, IgG specific antibodies, an increase in the level of expression of anti-inflammatory miR-146a, a decrease in the level of expression of pro-inflammatory miR-155 which may signify the strengthening of antiviral control. The study data demonstrated the decrease in the expression of miR EBV (BART-13 and BART-15) and TLR9 on the immunocompetent cells that can also be attributed to the criteria for IP effectiveness. The effectiveness of IP was also proved by the stabilization of cell mechanisms, namely the tendency to normalizing T and B cell populations, decrease in the number of natural killer cells and activated cells (CD25+, CD3+ HLA DR+). On the other hand, the number of lymphocytes with suppressor activity (CD4+25+) remained significantly high mitigating autoimmune aggression. The results of the study show that the use of IP for treating the acute phase of EBV infection contributed to the decrease of repliсative activity of the virus; suppressing the aggressiveness of autoimmune reactions. The decrease in the expression of miR EBV (BART-13 and BART-15) can be recommended as a criterion for the IP effectiveness; the decrease in the expression of TLR9 on immunocompetent cells –as a criterion for suppressing autoimmune reactions.

Immunocompetent cells in the tissue of adhesives of patients with adhesion process in the small pelvis

Objective: To study the morphological features and subpopulation composition of immunocompetent cells of adhesion tissue in women with adhesions of the pelvic organs.Materials and Methods: Th e study was carried out using surgical material obtained from 70 women aged 23 to 40 years. Of these, 50 tissue samples of peritoneal adhesions from patients with adhesions of organs in the small pelvis of I – II degree who underwent adhesiolysis and 20 samples of parietal peritoneum from healthy women who underwent endoscopic sterilization for contraception or completion of generative function. Th e authors used histological, immunohistochemical, and morphometric research methods.Results: Immunological changes in adhesion tissue were characterized by the activation of the T-cell link of immunity. It was confi rmed by a signifi cant increase in the content of CD4+ (p <0.001), CD8+ (p <0.001), a shift in the balance of immunoregulatory subpopulations towards CD8+, a lower indicator of the immunoregulatory index (p = 0.015), and insuffi ciency of the humoral link of immunity, namely, the absence of CD20+ content against the background of a slight increase in the CD138+ pool.Conclusion: To prevent the postoperative adhesion process in the small pelvis in patients of reproductive age, it is necessary to apply immunomodulatory therapy in the early postoperative period, which will improve the results of surgical treatment and is pathogenetically justifi ed.