Vol 21, No 2 (2018)
- Year: 2018
- Published: 15.04.2018
- Articles: 10
- URL: https://rusimmun.ru/jour/issue/view/4
REVIEWS
HOMEOSTATIC PROLIFERATION: FROM HEALTH TO PATHOLOGY
Abstract
In this review, we summarized contemporary knowledge about homeostatic maintenance and homeostatic proliferation of effector and regulatory T-cells, which are two main branches of the immune system that provide immune equilibrium and tolerance. Homeostatic proliferation is a normal physiological process caused by lymphopenia to maintain a constant level of T-cells in the periphery, but sometimes it may acquire pathological traits. Here we will discuss mechanisms of positive and negative influences on immunity during homeostatic proliferation, which may arise in different conditions. We supposed here, that the main of these conditions are decreased thymic output and deep lymphopenia, which lead to fast expansion of T-effectors with high-affinity T-cell receptor to self-antigens, and to inhibitory impacts on T-regulatory lymphocytes by increased levels of homeostatic cytokines that eventually raises a risk of development different autoimmune processes.
91-105
INTERLEUKIN‑7
Abstract
Interleukin 7 (IL‑7) is a protein that in humans is encoded by the IL7 gene. IL‑7 is a hematopoietic growth factor secreted by stromal cells in the bone marrow and thymus. It is also produced by keratinocytes, dendritic cells, hepatocytes, neurons, and epithelial cells but is not produced by normal lymphocytes. IL‑7 stimulates the differentiation of multipotent (pluripotent) hematopoietic stem cells into lymphoid progenitor cells. It also stimulates proliferation of all cells in the lymphoid lineage (B cells, T cells and NK cells). IL‑7 is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre‑pro‑B cell growth‑stimulating factor. IL‑7 binds to the IL‑7 receptor, a heterodimer consisting of Interleukin‑7 receptor alpha and common gamma chain receptor. Binding results in a cascade of signals important for T‑cell development within the thymus and survival within the periphery. Knockout mice which genetically lack IL‑7 receptor exhibit thymic atrophy, arrest of T‑cell development at the double positive stage, and severe lymphopenia, increases in B and T cells.
106-117
ORIGINAL ARTICLES
A STUDY ON THE ASSOCIATION OF IL‑1RAVNTR AND IL‑1α (С+889T) GENE POLYMORPHISMS WITH FEATURES OF ESSENTIAL HYPERTENSION
Abstract
Objective: the analysis of the relationship between polymorphisms IL1-raVNTR, С+889T gene IL-1α and features of essential hypertension (the risk myocardial infarction and stroke among men and women).
Methods: The 300 patients with II stage essential hypertension were followed for 8 years. Polymorphism of cytokine genes (IL-1ra (86 bp VNTR),–889C/T IL-1α) were examined by the method restrictor analysis of amplification products specific regions of the genome. Concentrations of IL-1ra, IL-1α in serum were measured by ELISA (test systems eBioscience (Bender MedSystems)).
Results: Genotyping of interleukin 1 receptor antagonist genes (IL-1ra86bp VNTR) has shown positive associations between the intron 2 IL-1ra – 4R/4R, 5R/5R microsatellite polymorphism and the risk of arterial hypertension development. The 5R/5R, 2R/2R were associated significantly with risk of stroke and myocardial infarction in patients with essential hypertension. Patients with polymorphisms of IL-1ra 4R/4R and 5R/5R have a lower concentration of IL-1Pa and higher levels of IL-1α in serum than otherpatients. Variant TT polymorphism –889C/T IL-1α is correlated with an increase in the concentration of IL-1α in the serum, without changing the frequency of hypertension, but increases the risk of myocardial infarction and stroke in patients with hypertension (mostly women). Allele 4R/4R (IL1-raVNTR) is associated with hypertension and its combination with – TT variant with IL-1alpha (C + 889T) polymorphisms contribute to the development of myocardial infarction and stroke in women.
118-127
INFLUENCE OF MURAMYL DIPEPTIDE DERIVATE (GMDP-A) ON NOD-2 EXPRESSED TUMOUR CELL LINES
Abstract
Muramyl dipeptides (MDP) are the multiple repeating structural unit of a cell wall peptidoglycan of all the bacteria, which possess the ability to interact with cytoplasmic receptors of the NOD family in human cells and induce activation of the innate immunity. This makes them the promising compounds for the development of drugs for immunomodulating therapy and in particular for biotherapy of tumors. However, there exists data on the expression of MDP targeting NOD receptors in tumor cells and association of some types of cancer with different polymorphic variants of these receptors. In this connection, the purpose of the reported study was to investigate the effect of MDP synthetic analogue, i. e. GMDP-A on the proliferative capacity of NOD2-expressing tumor cell lines of various origin, and the effect of the combined use of GMDP-A with cisplatina. As a result of the performed studies, it has been demonstrated that GMDP-A (at the doses of 1, 5, 10, 20 and 40 μg/ml) itself and GMDP-A in combination with cisplatina exerted differently directed effects.
128-140
ANTIBODIES TO BENZO[A]PYRENE AND ESTRADIOL AND THE GENE POLYMORPHISMS OF CYTOKINES AT MALE LUNG CANCER
Abstract
The associations of antibodies to benzo[a]pyrene and estradiol (IgG-Bp, IgG-Es) with IL1B(rs1143634, rs16944), IL1RN(VNTR, intron 2), IL4 (VNTR, intron3), IL6 (rs1800795), IL10 (rs1800896), TNFA (rs1800629, rs361525) gene polymorphisms in 228 smoking healthy men (NM) and 657 lung cancer patients (LCP)were studied. There was revealed association of gene polymorphism only of TNFA (rs1800629) with LC, but not others cytokines. LC risk in GG carriers was high (OR = 1,1–2,3; p = 0,007) and in GA carriers was low (OR = 0,4–0,9; p = 0,01). LC risk was low (OR = 0,3–0,7; p = 0,0002) when both IgG-Bp and IgG-Es were absent. LC risk was high (OR = 1,8–4,4; p = 0,0001) when levels both IgG-Bp and IgG-Es were increased. IgG-Bp and IgG-Es formation was associated with TNFA (rs361525) gene polymorphism in HM (p = 0,007), and with IL1RNVNTR genepolymorphism (p = 0,003) and IL1B(rs16944) (p = 0,007) in LCP. There have first reported a relationship between cytokines gene polymorphisms and specific immune responses on chemical carcinogens and endogenous steroids in healthy donors and lung cancer patients. Immunoassays of IgG antibodies to Bp and Es combined with molecular-genetic studies of TNFA (rs361525), IL1RNVNTR and IL1B (rs16944) are recommended for the lung cancer risk assessment.
141-149
CD56 EXPRESSION BY PERIPHERAL BLOOD CYTOTOXIC T CELLS IN MULTIPLE SCLEROSIS
Abstract
Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. Recent reports have shown CD3+CD8+ and their different subsets take part in neuroinflammation. During the current study frequency, phenotype as well as CD56 and CD57 expression of peripheral blood CD3+CD8+ cells derived from healthy volunteers (n = 52), MS subjects during relapse (n = 31) or remission (n = 20) were characterized using ten-color flow cytometry. CD3+CD8+ were divided into naïve, central (CM) and effector memory (EM), as well as effector cells (TEMRA) based on the expression of CD45RA, CD62L, CD27 and CD28. No differences were observed during the comparison of N, CM and TEMRA CD3+CD8+ subsets relative and absolute number between the groups, but the number of CM cells was decreased in MS groups The relative and absolute number of “naïve” CD3+CD8+ cells were inversely related (r = –0,512, р = 0,003 and r = –0,430, р = 0,014, respectively) to the degree of disability of examined patients. The percentages of CD57+ cells were increased only within naïve and CM subsets in both MS groups compared with healthy volunteers. While the relative numbers of CD56+ cells were significantly evaluated in all investigated cytotoxic T cell subsets in MS group with the exception of TEMRA cells from patients during remission in comparison with control group. Our data demonstrate that CD56 level on CD3+CD8+ subsets may represent a biomarker of neuroinflammation in MS patients.
150-159
FEATURES OF INTRACELLULAR ENZYMES ACTIVITY INFLUENCE ON THE RESPIRATORY BURST STATE OF NEUTROPHILES AT THE FOLLOWING DEVELOPMENT OF SEPSIS IN PATIENTS WITHWIDESPREAD PURULENT PERITONITIS
Abstract
The purpose of the research was to study the features of the respiratory burst activity and NAD(P)-dependent dehydrogenases activities in blood neutrophils in the forecast of the development of abdominal sepsis in patients with widespread purulent peritonitis (WPP). The study involved 50 patients with WPP in the preoperative period. Abdominal sepsis was developed by 35 patients (70.0%) from 5 to 10 days postoperative period, 15 patients (30.0%) hadn’t complications. The respiratory burst condition of blood neutrophils was examined using a chemiluminescent assay. Intracellular activity of the NAD(P)-dependent dehydrogenases was researched with using bioluminescent methods. It was found that patients with WPP whose dynamics of the preoperative period will develop sepsis the chemiluminescent activity of blood neutrophils was characterized by a reduced level of spontaneous synthesis of the primary reactive oxygen species (ROS) and elevated levels of spontaneous synthesis of secondary ROS relative of the indicators identified in patients without subsequent complications. The feature of neutrophil metabolism in WPP patients without subsequent development of sepsis was high activity of the anaerobic lactate dehydrogenase reaction and decrease in activity of the NADP-dependent decarboxylating malate dehydrogenase. In patients with WPP and the subsequent development of sepsis was found high level of NAD-dependent substrates outflow citric acid cycle in the reaction of amino acid metabolism via glutamate dehydrogenase that may affect the activity of aerobic respiration in the neutrophils. Using correlation analysis was found that the intensity of the neutrophils respiratory burst in patients with no subsequent complications depends on the activity of anaerobic glycolysis. Patients with subsequent development of sepsis in the blood neutrophils were detected competitive relationship between the levels of primary and secondary ROS synthesis and enzyme activity.
160-169
CLINICAL, IMMUNOLOGICAL CRITERIA AND LABORATORY MARKERS OF ATYPICAL CHRONIC ACTIVE INFECTION CAUSED BY THE EPSTEIN-BARR VIRUS
Abstract
Today, an atypical chronic active infection caused by herpesviruses and, in particular, the Epstein-Barr virus is polysymptomatic and polysyndromic. It is also a difficult to diagnose and poorly understood disease. Patients suffering from this disease often turn to specialists of various profiles. However, the disease is often not diagnosed and the patients remain without a correct diagnosis and, consequently, without an adequate therapy. The revealed clinical and immunological criteria and laboratory markers of this persistent viral infection allowed developing a diagnostic algorithm that is used to establish a correct diagnosis of atypical chronic active infection caused by the Epstein-Barr virus. In addition, features of the immune system functioning and interferon status in this infection have been detected. The main features are the defects of the induced production of IFNα and IFNγ, deficiency of cytotoxic T lymphocytes, of natural killer cells, including EKT, and / or inadequate absence of activation, neutropenia. In general, the revealed clinical diagnostic and immunopathogenetic features of the course of atypical chronic active infection caused by the Epstein-Barr virus, as well as the developed algorithm, will further allow to create the concept of an individualized / personified, complex etio- and immunopathogenetic, targeted therapy of this atypical, often invalidating viral infection. The development of methods for the rehabilitation of the body's antiviral protection system and the interferon system will lead to a significant reduction or complete suppression of the replicative activity of EBV. That will allow the return of control of the immune system, as well as interferon systems over EBV and other herpes-viral infections.
170-177
NEWS FROM RUSSIAN SOCIETY OF IMMUNOLOGY
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