Vol 21, No 1 (2018)

Cover Page

REVIEWS

CO-INHIBITORY MOLECULES IN NORMAL AND PATHOLOGICAL CONDITIONS. IMMONOLOGICAL CHECKPOINTS. Part 2. Co-inhibitory molecules part in oncology and infectious diseases. Checkpoints’ blockers monoclonal antibodies

Toptygina A.P.

Abstract

The differentiation and protective capacity of antigen‑specific T‑cells are regulated by both positive and negative signals. Molecules of the B7/CD28 family are very important for regulating T‑cell activation and peripheral tolerance. In particular, PD‑1, CTLA‑4 and other co‑inhibitory molecules play an active role in dampening of excessive immune activation which is critical for successful clearance of a pathogen without harm to the host. These co‑inhibitory molecules (immunological checkpoints) are essential for inducible Treg differentiation and function. On the other hand, overexpression of co‑inhibitory molecules can lead to T‑cell exhaustion, an adaptive property that occurs in T‑cells due to persistent systemic antigen exposure. Exhausted T‑cells are described as effector T‑cells with decreased cytokine expression and effector function. Here, we review a critical role of co‑inhibitory molecules which they play in immunopathogenesis of four immunological syndromes: allergy, autoimmune diseases, chronic infection, and cancer. Reversal of exhausted T‑cells by blocking co‑inhibitory pathways has become an important area due to its therapeutic applications in oncology and chronic viral infections.

Russian Journal of Immunology. 2018;21(1):3-16
pages 3-16 views

MORPHOFUNCTIONAL CHARACTERISTICS OF THE PROTECTIVE MECHANISMS OF NEUTROPHILS AGAINST BACTERIAL INFECTIONS AND THEIR CONTRIBUTION IN THE PATHOGENESIS OF PRO-INFLAMMATORY REACTIONS

Matosova E.V., Andryukov B.G.

Abstract

Infection is one of the leading causes of mortality and morbidity in the world. Neutrophils are an active and numerous effector link in the innate immune system, which protects the body from infection with pathogenic microorganisms. However, the contribution of neutrophils in the development of the infectious process was underestimated, despite the fact that the functions of this subclass of leukocytes have long been known as a pathogenetic element of inflammation. In addition to phagocytosis, these cells can mediate lesser-characterized antibacterial strategies – extracellular degranulation, and also, by releasing extracellular chromatin, nuclear protein and serine proteases, to form web-like fiber structures called neutrophilic extracellular traps (NETs). NETs can capture pathogens, cause endothelial dysfunction and pro-inflammatory immune responses. The phenomenon of NETs is a relatively new form of programmed cell death (NETosis), the significance of which in the development of the infectious process and the development of inflammation is not fully understood. NETosis has a high potential for further study of the pathogenesis of inflammation and the search for effective methods of treating infections. This review focuses on modern data on the basic protective strategies of neutrophils against bacterial infections and their contribution to the pathogenesis of proinflammatory reactions. Modern approaches to pharmacological modulation of various variants of antimicrobial mechanisms of neutrophils are discussed, which is promising in cases of complex treatment of infections associated with antibiotic-resistant strains of bacteria.

Russian Journal of Immunology. 2018;21(1):17-27
pages 17-27 views

ORIGINAL ARTICLES

FEATURES OF THE REGULATORY INFLUENCES OF THE ARGINYL-ALPHA-ASPARTIL-LIZIL-VALYL-TYROSIL-ARGININ ON THE INTACT AND EXPERIMENTAL TRANSFORMED PHENOTYPE CD62L+CD63+CD66d+ OF NEUTROPHILIC GRANULOCYTES

Nesterova I.V., Nguyen T., Khajdukov S.V., Chudilova G.A., Lomtatidze L.V.

Abstract

The experimental model of the in vitro transformed phenotype of neutrophilic granulocytes (NG) equipped with receptors CD62L, CD63, CD66d, was created under the influence of N-formyl-methionyl-leucyl-phenylalanine (fMLP). The features of the transformed phenotype of NG were described. The influence of the hexapeptide arginyl-alpha-aspartyl-lysyl-poured-tyrosyl-arginine on untransformed and transformed phenotype of NG was investigated in vitro. It was shown that fMLP reduces the number of NG, expressing the receptor CD62L and reduces the density of expression of this receptor on the surface membrane of NG, moderately increases the density of CD63 and moderately increases the number of CD66dL+NG. Hexapeptide does not influence on the number of untransformed NG, bearing receptors CD62L, CD63, CD66d, and the level of the expression of those molecules. It has been shown the mitigation of the influences of fMLP after the simultaneous incubation NG with fMLP and hexapeptide: the number of CD62L+NG was increased and the density of membrane expression of the molecules of CD62L was increased too. At the same time, hexapeptide did not correct the negative effects of fMLP on the number of CD63+NG and CD66d+NG, and on level of density of the expression of CD63 and CD66d molecules on the surface membrane of NG. Overall, the results demonstrate the classic immunomodulatory effect of hexapeptide: on the one hand, we saw the absence of any changes of the studying receptors on membrane of the untransformed NG under hexapeptide influences, and on the other hand, it was demonstrated a strong trend of leveling the negative transformational effects of fMLP under hexapeptide influences.

Russian Journal of Immunology. 2018;21(1):28-34
pages 28-34 views

A META-ANALYSIS OF THE RESEARCH OF THE CONCENTRATION OF IL-17 IN PERIPHERAL BLOOD OF PATIENTS WITH INFLUENZA A (H1N1) pdm09

Shipilov M.V., Tutelian A.V.

Abstract

Interleukin‑17 (IL‑17) is one of the inflammatory cytokines, which enhances including the effects of other pro‑inflammatory cytokines. In order to increase the statistical power and increase the reliability of the results according to various researchers, including as a result of its own research, conducted a meta‑analysis (a quantitative systematic review) study of IL‑17 in peripheral blood of patients with influenza A (H1N1) pdm09. Question: to determine with a high level of confidence, whether IL‑17, a marker of prognosis of influenza A (H1N1) pdm09. Searches were carried out research work on this subject in a variety of electronic databases (Medline, EMBASE, the Cochrane Controlled Trials Register, and others.), in dissertations, journals, thematic reviews, conference proceedings and other sources. 3 scientific papers were selected that met the criteria for inclusion / non‑inclusion in the study (characteristic of scientific papers, diagnostic criteria, age of patients, comparable groups of patients, the presence of self‑control, comparable research methodology, statistical criterion and the total number of independent studies). Selected studies have shown sufficient uniformity (homogeneity) comparison groups. This meta‑analysis of scientific papers showed that the determination of serum IL‑17, patients with severe influenza A (H1N1) pdm09 allows a high probability of predicting a favorable outcome. At the same time, the frequent unfavorable outcome of the disease (with a probability of 90% or more) indicates the absence in the serum of patients with influenza A (H1N1) pdm09 IL‑17 (below the threshold of sensitivity of diagnostic test kits). Thus, the results of a meta‑analysis of IL‑17 level in the blood can be used in clinical medical practice for quite simple and convenient prognosis marker of influenza A (H1N1) pdm09.

Russian Journal of Immunology. 2018;21(1):35-39
pages 35-39 views

COMBINATION EFFECTS OF ANTIBODIES TO BENZO[A]PYRENE, ESTRADIOL AND PROGESTERONE ONTO CONCENTRATIONS OF FEMALE SEX HORMONES IN BLOOD SERUM OF THE BREAST CANCER PATIENTS

Glushkov A.N., Polenok E.G., Kostyanko M.V., Rogozin A.I., Antonov A.V., Verzhbitskaya N.E.

Abstract

Antibodies to benzo[a]pyrene, estradiol and progesterone (IgA-Bp, IgА-Es и IgA-Pg) as well as concentrations of Es and Pg were studied in the blood serum of 346 non-smoking breast cancer patients in post menopause. There were no any associations between IgA-Bp and hormones concentration. The high levels of Es and Pg were found when IgА-Es and IgA-Pg were increased correspondingly (p = 0,02 and p = 0,002). The high concentrations of Es and Pg as well as high ratio of Pg/Es were revealed when ratio IgA-Bp/IgА-Es were high (p = 0,003; p = 0,003 and p = 0,0002 correspondingly). So IgA-Bp modulated the effects of IgА-Es onto concentrations of Es and Pg as well as hormonal balance in breast cancer patients. There were no any associations between the revealed immune-endocrine effects with the tumor stages, metastases and Es/Pg receptors.

Russian Journal of Immunology. 2018;21(1):40-45
pages 40-45 views

A CASE OF CVID PATIENT: EXOME SEQUENCING REVEALED HETEROZYGOUS MISSENSE MUTATION E1021K IN THE PIK3CD GENE

Gordukova M.A., Kechin A.A., Zimin S.B., Serpokrylova I.Y., Filipenko M.L., Prodeus A.P.

Abstract

To establish a definitive molecular diagnosis for the case of a 17-Year-Old Boy (NS) with a history of CVID, recurrent pulmonary infections, chronic EBV viremia, lymphadenopathy and a decrease of IgG3 and luck of IgG4 who presented for follow-up in the immunodeficiency clinic whole exome capture and next-generation sequencing were performed. We showed a presence of heterozygous missense mutation E1021K in the PIK3CD gene that encodes p110d (c.3061G > A [p.E1021K]). The mutation was verified by Sanger sequencing and not found in parents genomic DNA, thus classifying this E1021K mutation as de novo. Several additional mutations relevant to immune system pathways were found and confirmed by Sanger sequencing including TLR3 p.L412F, TNFRSF1A p.R121Q (rs4149584), associated with periodic disease.

Russian Journal of Immunology. 2018;21(1):54-64
pages 54-64 views

IMMUNOLOGICAL RISK FACTORS OF DEATH IN DIABETES

Asfandiyarova N.S.

Abstract

Objective: we investigated immunological risk factors for death in patients with diabetes mellitus (DM).

Material and Methods: In a prospective cohort study included 337 patients with impaired glucose metabolism (36 – with impaired fasting glucose or impaired glucose tolerance, 80 – with type 1 diabetes, 194 – with type 2 diabetes, 27 – with diabetes due to chronic pancreatitis). Average follow-up was 11,2 ± 4,8 years. The level of antibodies, circulating immune complexes, the presence of antibodies to islet cells; number of CD3+, CD4+, CD8+ lymphocytes and the proliferation activity of the lymphocytes in response to PHA, insulin.

Results: During the follow-up period 115 patients died. The most common cause of death in patients with diabetes was cardiovascular diseases and cancer. The levels of immunoglobulins and circulating complexes are not informative for prognosis. Lack of autoimmune reactions and decreased lymphocyte proliferation in response to PHA are the risk factorsfor death in type 1 diabetes. Autoimmune response to insulin, suppressed by prostaglandin synthesizing cellshas a protective effectin type 2 diabetes.

Conclusion: Cell-mediated immunity to insulin, islet cell antibodies, reduction of proliferative activity in response to the PHA are unfavorable prognostic factors in patients with impaired carbohydrate metabolism.

Russian Journal of Immunology. 2018;21(1):65-72
pages 65-72 views

MECHANISMS OF ANTI-INFLAMMATORY EFFECT OF GLYCOSYLATED POLYPEPTIDE COMPLEX EXTRACTED FROM SEA URCHIN STRONGYLOCENTROTUS DROEBACHIENSIS

Katelnikova A.E., Kryshen K.L., Makarova M.N., Makarov V.G., Shikov A.N.

Abstract

The results of research on two models of acute bronchitis induced by cigarette smoke and formaldehyde, in rats the substance of glycosylated polypeptides complex (GPC) provided anti-inflammatory effect. Based on these data, a search of anti-inflammatory action mechanisms of GPC. The aim of the study was to investigate the activity of GPC obtained from viscera of sea urchins S. droebachiensis on two cyclooxygenase isoforms (COX1 and COX2), 5 – lipoxygenase (5-LOX), lipopolysaccharide (LPS)-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation, toll-like receptor 4 (TLR4). COX1/2 and 5-LOX activity studied using commercial kits (Cayman Chemicals, USA). GPC effects on LPS-induced p38 MAРK phosphorylation were studied using human monocyte cellline U937. To assess the interaction of GPC with toll-like receptor 4 (TLR4) cell line HEK-Blue-hTLR4 (Invivogen, USA) was used. Results of the study showed that GPC inhibited COX2 activity with IС50 67 µg/ml. Also, GPC inhibited LPS-induced p38 MAРK phosphorylation by blockade of TLR4 with ЕС50 2.7 µg/ml. In the other hand, GPC did not affect the activity of COX1 and 5-LOX. The obtained results allow to conclude that targets of GPC anti-inflammatory action are: COX2, of p38 MAРK and TLR4.

Russian Journal of Immunology. 2018;21(1):73-79
pages 73-79 views


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