Postischemic neuroinflammation is a critical pathophysiological process within the entire pattern of cerebral ischemia. It is characterized by microglial and astroglial activation and is accompanied by disturbances in the innate and adaptive immune response. The early damage of the blood-brain barrier (BBB) integrity is accompanied by the brain autoantigens release into circulation, in particular, the neurospecific protein S100B. According to recent experimental data, activated autophagy is associated with postischemic neuroinflammation, involved in its regulation and influences the outcome of the ischemic stroke (IS) acute period. Experimental evidence is provided for the autophagy involvement in the regulation of proinflammatory cytokines and chemokines production. The influence of activated autophagy on the pro- and anti-inflammatory cytokines balance in acute IS has been demonstrated. Purpose of the study: to quantitatively evaluate key autophagy biomarkers, the early biomarker of BBB damage S100B, pro- and anti-inflammatory cytokines in the dynamics of the IS acute period. To identify the relationship between autophagy and inflammation biomarkers, 112 patients with acute IS and 56 healthy persons were examined. Patients underwent dynamic clinical neurological examination and blood testing on the 1st, 7th and 14th days from the disease’s onset. The level of autophagy in peripheral blood leukocytes was determined by flow cytometry by assessing the intracellular expression of autophagy proteins LC3, p62 and mean fluorescence intensity of the Cyto-ID dye, which specifically recognizes active autophagosomes. Serum concentrations of TNFα, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-18, neuropeptide S100B and autophagy biomarkers Beclin-1, LC3, p62 were determined by ELISA. A statistically significant increase in the studied biomarkers was found compared to the control group. The maximum increase in inflammation indicators and neuropeptide S100B was observed on the 1st, and autophagy biomarkers – on the 7th day of the disease. Established correlations indicate the participation of activated autophagy in the postischemic neuroinflammation regulation and its involvement in ischemic brain damage in the early stages of the IS acute period (days 1-7).

Postischemic neuroinflammation is a critical pathophysiological process within the entire pattern of cerebral ischemia, spanning early injury and tissue repair. According to recent experimental data, autophagy is involved in the regulation of neuroinflammation, influencing the outcome of the acute period of ischemic stroke (IS).Objective. To evaluate the relationship between autophagy biomarkers and inflammation indicators in the dynamics of the acute period of atherothrombotic IS.Materials and methods. 112 patients in the acute period of newly developed atherothrombotic IS and 56 donors (control group) were examined. Patients underwent dynamic clinical and neurological examination on the 1st, 7th and 14th days from the onset of the disease (magnetic resonance imaging, testing using the NIHSS scale, modified Rankin scale). At the same time intervals, blood was drawn for testing. The number of active autophagosomes in peripheral blood was assessed by flow cytometry using a specific Cyto-ID dye. The serum concentrations of proinflammatory cytokines IL‑1β, IL‑8, IL‑18 (interleukins‑1β, -8, -18), TNFα (tumor necrosis factor-α), autophagy biomarkers Beclin‑1, LC 3 and p62 were determined by enzyme-linked immunosorbent assay analysis. C-reactive protein was assessed by a highly sensitive immunoturbidimetric method.Results. A statistically significant increase in the studied parameters was revealed compared to the control group. The maximum increase in inflammation biomarkers was observed on the 1st day, and the maximum increase in key indicators of autophagy (LC 3, Beclin‑1, Cyto-ID) – on the 7th day after the development of ischemia. A direct relationship was established between the level of autophagy and the concentration of inflammatory biomarkers (CRP, IL‑1β, IL‑18, TNF-α) on the 1st and 7th days of acute IS.Conclusions. The identified correlations indicate the participation of activated autophagy in the regulation of post-ischemic neuroinflammation and its involvement in ischemic brain damage in the early stages of the acute period of IS (days 1–7). The results obtained confirm the literature data on the influence of autophagy on the outcome of the acute period of the disease.

The postischemic inflammatory response plays a significant role in the pathogenesis of acute ischemic stroke (IS). It has been established that acute IS is accompanied by aseptic inflammation, which induces the activation of costimulatory molecules in the process of innate immunity response to brain tissue damage. The constantly progressive destruction of neuronal antigens contributes to an increase in the volume of the ischemic lesion. Evidence continues to accumulate indicating an important role of NLRP3-mediated inflammation in the pathogenesis of IS. It has been shown that autophagy is involved in the inflammatory cascade in acute IS. Many of the anti-inflammatory mechanisms mediated by autophagy in acute IS involve the key autophagic proteins Beclin-1, LC3, and p62. Experimental studies have shown that autophagy suppresses the activation of NLRP3 inflammation. Data on cross interactions between apoptosis and autophagy in the pathogenesis of IS are still controversial. The aim of the study was to evaluate the relationship between biomarkers of autophagy, inflammation, and apoptosis in the dynamics of the acute period of atherothrombotic IS. The article presents the results of a dynamic study of the serum concentration of the key autophagy biomarkers Beclin-1, LC3 and p62, apoptosis indicators Bcl-2 and p53, pro-inflammatory cytokines IL-1β, TNFα, IL-8, IL-18 which are involved in postischemic neuroinflammation. A statistically significant increase in the studied parameters was established in comparison with the control group. The maximum increase in the studied biomarkers is noted on the 1st day after the development of ischemia in patients with a severe course of the disease. The relationship between autophagy activity, apoptosis biomarkers, and some indicators of the systemic inflammatory response in patients with moderate and severe atherothrombotic stroke was revealed. The results obtained confirm the literature data on the involvement of autophagy in the regulation of the postischemic inflammatory response.

The immune status of 58 patients with gliomaswas evaluated. Prior to surgical treatment in patients with low-grade gliomas was observed higher (p ˂0.05) the absolute number of total T-lymphocytes, Thelper cells and NK-cells compared to patients with high grade glioma. Postoperatively group grade II was observed explicit reduction in the number of CD3 + , CD3 + CD4 + , CD3 – CD56 + and increase in the population CD3 + CD8 + cytotoxic T-lymphocytes. Reducing of the number of CD3 – CD56 + lymphocytes in patients with diffuse astrocytomas and anaplastic gliomas after surgical treatment, maybe, related to the migration of these cells into the area of surgical intervention. At the same time in patients with grade III, IV gliomas was revealed an increase of the absolute number of killer T-cells. In the group of grade IV also was recorded increase in the percentage of T-reg, having a suppressor function, which may indicate a breach of anti-tumor immune response and cause suppression of the cytotoxic response in patients with highgrade gliomas.

Цель исследования: изучить влияние очагов хронической инфекции (ОХИ) на иммунный статус больных псориазом. Материалы и методы. Обследованы 30 больных псориазом в возрасте от 19 до 61 года (у 21 человека диагностирован бляшечный псориаз, у 9 — каплевидный псориаз), которые были разделены на 2 группы. В первую группу вошли больные с выявленными очагами хронической инфекции (18 человек), во вторую — без наличия очагов хронической инфекции (12 человек). Группу контроля составили 15 практически здоровых лиц, поступивших в клинику для удаления доброкачественных новообразований кожи. Всем пациентам проведено комплексное клиническое, инструментальное и лабораторное обследование, а также выполнена иммунограмма. Определение субпопуляций лимфоцитов проводилось на проточном цитометре Cytomics FC500 фирмы Beckman Coulter с использованием различных комбинаций прямых моноклональных антител и изотопических контролей. Сравнение групп проводили с использованием непараметрического критерия Манна — Уитни, различия считали значимыми при p < 0,05. Результаты. Показано отсутствие выраженных количественных изменений со стороны основных и малых субпопуляций Т- и В-лимфоцитов в обеих группах больных псориазом. В то же время группа больных псориазом, имеющих ОХИ, отличалась повышением относительного количества Т-лимфоцитов (p = 0,034) и Т-хелперов (p = 0,012), относительного и абсолютного количества активированных CD3+HLA-DR+-клеток (p = 0,028 и 0,036 соответственно), а также уменьшением регуляторных T-хелперных клеток (p = 0,031). Субпопуляция тропных к коже CLA+CD3+-лимфоцитов в сравнении с контролем была повышена как в первой (p = 0,016), так и во второй (p = 0,044) группах. Также больные псориазом отличались от практически здоровых лиц повышением количества Т-клеток памяти (p = 0,049 для 1-й группы, p = 0,003 для 2-й группы). Заключение. Существующие очаги хронической инфекции у больных псориазом приводят к дисбалансу в содержании отдельных субпопуляций лимфоцитов: повышению относительного количества CD3+CD4+ и CD3+HLA-DR+ клеток, а также уменьшению регуляторных Т-хелперных клеток. Данные изменения могут приводить к длительному течению заболевания и сокращению периодов ремиссии.

Objective: to study the influence of focal infection on the immune status of patients with psoriasis.Materials and methods. 30 patients with psoriasis aged 19 to 61 years (21 people — plaque psoriasis, 9 people — psoriasis guttata) were examined, which were divided into 2 groups. The first group — with the diagnosed of focal infection (18 people), the second group — without the presence of focal infection (12 people). The control group consisted of 15 healthy individuals admitted to the clinic for the removal of benign skin tumors. All patients underwent a comprehensive clinical, instrumental and laboratory examination, as well as an immunogram. Determination of lymphocyte subpopulations was carried out on a flow cytometer “Cytom - ics FC500” by Beckman Coulter using various combinations of direct monoclonal antibodies and isotopic controls. The groups were compared using nonparametric Mann — Whitney test, the differences were considered significant at p < 0.05.Results. The absence of significant quantitative changes in the main and small subpopulations of T- and В-lymphocytes in both groups of patients with psoriasis was shown. At the same time, the group of patients with psoriasis and focal infection, was characterized by an increase in the relative number of T-lymphocytes (p = 0.034) and T-helpers (p = 0.012), the relative and absolute number of activated CD3+HLA-DR+cells (p = 0.028 and 0.036, respectively), as well as a decrease in regulatory T-helper (p = 0.031). Subpopulation of CLA+CD3+-lymphocytes tropic to the skin in comparison with control was increased both in the first (p = 0.016) and second (p = 0.044) groups. Also, patients with psoriasis differed from healthy individuals by increasing the number of memory T-cells (p = 0.049 for group 1, p = 0.003 for group 2).Conclusion. Existing focal infection in psoriasis patients lead to an imbalance in the content of individual lymphocyte subpopulations: an increase in the relative number of CD3+CD4+ and CD3+HLA-DR+ cells, as well as a decrease in regulatory T-helper. These changes can lead to a long course of the disease and a reduction in remission periods.

The idea of CLA+T-lymphocytes, which are a special subpopulation of cells with a tropic to the skin, is given. The issues of maturation, migration and functional features of CLA+T-cells are considered. Special attention is paid to the different phenotype of memory T-cells. Modern data concerning the role of CLA+T-cells in the pathogenesis of autoimmune and allergic dermatoses, as well as malignant skin tumors are also presented. The conclusion about the necessity of further study of CLA +T-lymphocytes for detailed understanding of pathogenesis and search of variants of targeted therapy in psoriasis, atopic dermatitis, skin lymphomas and other skin diseases is made.

The idea of CLA+T-lymphocytes, which are a special subpopulation of cells with a tropic to the skin, is given. The issues of maturation, migration and functional features of CLA+T-cells are considered. Special attention is paid to the different phenotype of memory T-cells. Modern data concerning the role of CLA+T-cells in the pathogenesis of autoimmune and allergic dermatoses, as well as malignant skin tumors are also presented. The conclusion about the necessity of further study of CLA +T-lymphocytes for detailed understanding of pathogenesis and search of variants of targeted therapy in psoriasis, atopic dermatitis, skin lymphomas and other skin diseases is made.

A study of the functional activity of platelets by flow cytometry is conducted in 11 patients with a diagnosis of AML are in clinical remission and 1 1 almost healthy volunteers. The functional activity of platelets was evaluated according to the dynamics of the number of glycoprotein receptors ( GP) IIb/IIIa on the platelet membrane and the percentage of platelets expressing P-selectin (CD62P) before and after induction 10 /тт ADP. The number of GP IIb/IIIa receptors on the platelet surface was evaluated by the mean fluorescence intensity. The average age of the subjects in the group of AML patients was 44,4±5,2 years in the control group, 38,5±6,8 years (p>0,05). In the group of AML patients platelet counts was 104,6±3,1 x109/L in the control group 210,5±20,8x109/L (p0,05) in the number of receptor GP IIb/IIIa before and after ADP stimulation in both groups have been identified. At the same time, there was no statistically significant difference (p

хромосомные нарушения ассоциированы со специфическим аберрантным иммунофенотипом лейкозных клеток. К наиболее частым хромосомным аномалиям, сопровождающимся характерными иммунофенотипическими особенностями при острых миелоидных лейкозах, относятся: t(8;21); inv(16) или t(16;16); t(15;17). у взрослых при В-лимфобластном лейкозе/лимфоме наиболее часто встречается хромосомная транслокация t(9;22)(q34;q11.2). Для иммунофенотипирования лейкозных клеток использована проточная цитометрия. В исследовании представлены случаи острых лейкозов, иммунофенотипические особенности которых указывали на присутствие конкретных рекуррентных генетических аномалий. так, обнаружение в образцах костного мозга больного популяции бластных миелоидных клеток с иммунофенотипом CD117+++, CD34+++, hlA-Dr+++, CD38+++, суМро+++, CD13dim, CD33dim, CD56+, CD19dim, CD7dim позволило предположить наличие транслокации t(8;21). у другого пациента были обнаружены 2 популяции лейкозных бластов: 1) незрелые клетки с высокой экспрессией антигенов CD34, CD117, с признаками гранулоцитарной дифференцировки; 2) более зрелые клетки, не экспрессирующие CD34, CD117, с признаками дифференцировки в направлении моноцитопоэза и гранулоцитопоэза с коэкспрессией антигена CD2, что указывало на повреждение в 16-й хромосоме (inv(16) или t(16;16)). В третьем случае присутствие бластной популяции с ярко выраженной гомогенной экспрессией панмиелоидного антигена CD33, более слабой экспрессией панмиелоидного антигена CD13 и раннего стадиеспецифического миелоидного маркера CD117, позитивной экспрессией антигенов CD9, CD64, cyMPo и негативной по экспрессии hlA-Dr дало возможность прогнозировать аномалию t(15;17). у всех пациентов с острыми миелоидными лейкозами предполагаемые хромосомные нарушения подтвердились генетическими исследованиями. у пациента с В-лимфобластным лейкозом с t(9;22)(q34;q11.2) опухолевые бластные клетки экспрессировали пан-В-клеточные маркеры СD19, суCD79а и специфический для данного варианта лейкоза набор антигенов CD10+++, CD13dim+, CD33dim+, CD66c+++, CD38–. Генетические исследования, проведенные позже, выявили t(9;22)(q34;q11.2).

In the present study factors of immune system in peripheral blood (PB) of patients with chronic hepatitis C (CHС) with the different degree of fibrosis were determined. Patients with CHC have been divided into groups, according to the stages of disease: weak fibrosis F1 (n=32), moderate fibrosis F2 (n=22), heavy fibrosis F3 (n=19) and cirrhosis of liver F4 (n=13). The following subpopulations of T-lymphocytes have been investigated: CD3+CD4+, CD3+CD8+, CD3+CD16+56+, CD3+CD25+, CD3+HLA-DR+, CD3+CD4+CD25+, CD3+CD8+CD25+, CD3+CD4+HLA-DR+, CD3+CD8+HLA-DR+, CD3+CD95+. Besides, the subpopulations of В-cells (CD19+, CD3CD25+, CD19+CD95+), Ig A, IgM, IgG, highly-, medial-, low-molecular circulating immune complexes (CIC), cytokines Th1 (IFN-γ),Th2 (IL-4, IL-10) types, as well as proinflammatory cytokines TNF-α, IL-1β were defined. This research showed that the patient with the high degree of fibrosis have the increased quantity NKT (CD3+CD16+56+) and total count of activated T-cells HLA-DR (CD3+HLA-DR+) and the tendency for growing percentages of activated cytotoxic T-cells (CD8+CD25+ and CD8+HLA-DR+), which reflects the evolution of autoimmune reactions as the disease continues.These results have shown that in the higher stages of fibrosis the patients with CHC increased activity of T-cells immunity and constant antigen-specific or non-specific stimulation of T-lymphocytes may play a significant role in pathogenesis of CHC.With the increase of the fibrosis degree in patient with CHС, levels of IgA, IgG, medium-, low-molecular CIC, cytokines IFN-γ, IL-10 were increasing and the quantity of activated B-cells (CD3–CD25+) were decreasing. The research shows the domination of the B-cells response while the function of B-lymphocytes are injured and also are observed Th1/Th2 disbalance at all stages of disease. Besides, the direct correlation between CD95-antigen (Fas/APO-1) and activated CD3+CD4+CD25+, CD3+CD8+CD25+, CD3CD25+ subsets of lymphocytes was found. The established changes of the factors of the immune system can be used as the prognostic criteria of CHC.

In this article, we describe immunophenotypical and cytogenetic features of tumor cells in the patient with chronic lymphocytic leukemia (CLL) and prolonged exposure to irradiation in the history. Finding of 0.67% to 0.73% of metaphases with dicentric chromosomes confirmed the effect of radiation in this patient. Chromosome banding with mitogen stimulation of peripheral lymphocytes revealed 2% of cells with 47,XY, +12 karyotype, while FISH detected the greater number of cells with trisomy 12 in interphase bone marrow cells and peripheral lymphocytes. Immunophenotyping of bone marrow cells revealed the difference from “classic” CCL, i.e. simultaneous low-positive CD22 and CD79b expression as well as CD38 expression on the surface of tumor cells.

Results of studies of immune response during hepatitis C virus (HCV) infection were reviewed in order to reveal immunologic markers of the disease progression. Genetic heterogeneity of HCV and immunogenetic features of the host determine heterogeneity of immune response to the virus and differences in the course of the disease and outcomes. Spontaneous elimination of HCV-infection in acute phase occurs due to vigorous and sustained multispecific Th1-response toviral antigens. During such response proliferation of virus-specific CD4+ T-cells and secretion of IFN-gamma by them are observed, otherwise chronic hepatitis develops. Great importance in persistence of HCV as well as in quantitative and functional suppression of HCV-specific CD8+ T-cells has increased number of CD4+ CD25+ regulatory T-cells. Cellular immune response plays a key role not only in the elimination of HCV, but also in liver pathology associated with HCV-infection. Progression of the process and shift to its chronic form are also associated with decrease of production of IFN-gamma, alpha, IL-2 by peripheral blood mononuclear cells and increase of TNF-alpha, IFN-gamma, IL-4, IL-2r levels in blood serum.