Abstract. Thrombospondin-1 (TSP-1) is an extracellular matrix glycoprotein that can positively or negatively regulate adhesion, motility, proliferation, and survival of various cell types, including cells of the immune system. It is secreted by numerous cell types, and its expression is predominant in areas of tissue injury or remodeling. Initially, TSP-1 was identified as one of the first endogenous inhibitors of angiogenesis. This factor is known to be a potent inhibitor of angiogenesis, as demonstrated by in vitro inhibition of endothelial cell proliferation and in vivo vascular growth. Since then, much has been learned about its ability to modulate cell behavior during embryonic development, to maintain normal homeostasis of adult organism, wound healing, immune response, tumor growth. TSP-1 is a large, trimeric, matricellular protein, composed of multiple structural domains that interact with a diverse array of receptors and molecules. Many hematopoietic and immune cells are able of both producing TSP-1 and responding to it. This review presents a current understanding on participation of TSP-1 in differentiation, maturation and functioning of immune cells. (Med. Immunol., vol. 10, N 6, pp 499-506).

 

Abstract. Mediators of inflammation may play a sufficient role in destabilization of atherosclerotic plaque, disturbing the balance between collagen formation and its degradation in fibrotic capsule. Using a transgenic murine model, the effects of induced inflammation upon expression of factors determining posttranslational modification and degradation of collagen, i.e., prolyl-4-hydroxylase, matrix metalloproteinases-2, -9 (MMP-2, -9), and tissue inhibitor of metalloproteinases (TIMP-1) were evaluated. It has been shown that, under significant increase of interferon-γ and interleukin-1β, the synthesis of prolyl-4-hydroxylase and MMP - 9 is decreased, whereas expression of collagen, MMP-2 and TIMP-1 genes was not changed. (Med. Immunol., vol. 10, N 6, pp 507-512).

Abstract. We have examined parameters of innate and adaptive immunity, as well as HLA profile in COPD patients living under the conditions of environmental zinc deficiency (Zn levels in the soil < 0.1 mg/kg, and dietary contents of zinc, 9.1 mg/d, as compared to normal lower limit of 15 mg/d). It was shown that the patients with COPD exhibited activation of adaptive humoral immunity, along with suppression of T cell-mediated response and decreased phagocytic activity of neutrophils. Carrier state of HLA-DRB1*11 и -DQB1*301 alleles in inhabitants of zinc-deficient areas is a predisposing factor for COPD development. Meanwhile, DRB1*01, DQА1*0101, DQВ1*0501 alleles may be suggested as markers of resistance to this disease. (Med. Immunol., vol. 10, N 6, pp 513-518).

Abstract. Three groups of patients were investigated as follows: 1st group, HIV-infected patients, 2nd group, patients with HIV-associated tuberculosis, the 3rd group, persons with pulmonary tuberculosis. The amounts of cytokines (TNFα, IL-6, IL-10) and their soluble receptors (SRp55 TNFα, SRp75 TNFα, SR IL-6) were evaluated in blood serum by solid-phase immuno-enzyme technique. The patients did not receive antiviral therapy before, or during the investigations. Some features are revealed reflecting a direction and significance of changes in immune reactivity of the patients. In the patients with tuberculosis, IL-10 and IL-6 levels were increased, along with pronounced rise of srIL-6, relatively low index of SRp75 TNFα and deficiency of SRp55 TNFα, associated with moderate increase in TNFα. In the patients with HIV and HIV-associated tuberculosis, the direction of alterations were found to be similar, except of IL-10, i.e., a hyper-production of TNFα and its soluble type I and II receptors, increased IL-6 level in combination with lack of its soluble receptor. Correlation analysis showed a strict dependence between TNFα and viral load in the patients with IVB and V stage of HIV, and HIV-associated tuberculosis that argues for significance of TNFα in pathogenesis of HIV-infection and its progression. We have found differential trends in dynamics of cytokines under study and their soluble receptors in the course of HIV-infection progression in the groups I and II of patients, that allowing us of elaborating additional diagnostic criteria of HIV-associated tuberculosis. (Med. Immunol., vol. 10, N 6, pp 519-526).

Abstract. The 18 patients with stomach cancer were investigated. This group was divided in to two groups 9 people in each: one with psychotherapeutic treatment 3 men and 6 women aged from 51 to 68 years (with III stage 8 patients and with I stage 1 patient); another one with surgical treatment (control subgroup) consists of 5 men and 4 women aged from 51 to 71 years (III stage).

A special method of hypnosuggestive therapy (HST) devised for this situation to modify psychosomatic disorders was used. A level of CD34+ was measured before HST and after 1 month and telomere length as well as apoptosis were measured in lymphocytes before HST and after 3, 5, 7, 9 and 11 weeks. In control group a telomere length in lymphocytes was measured. In both subgroups of patients with cancer a telomere lengths were 500 b.p. shorter than in donors before treatment. Consequently HST after 7 weeks treatment significant telomere length elongation on 1000 b.p. and apoptosis increase to 1,7% were found. Hereby these results have shown that hypnosuggestive therapy reintegrats immune system in cancer patients which discover new key points for psycho immunological investigations. (Med. Immunol., vol. 10, N 6, pp 527-534).

Abstract. A full-scale development of post-vaccinal immunity is determined by T and B cell-dependent immunological memory which is formed in response to vaccine injection. However, a capacity of existing and newly developed vaccines to stimulate T cell-dependent immunological memory is very poorly studied. Present work is a first attempt of analyzing this issue, with respect to effects of live mucosal influenza vaccine.

The study involved fifty-seven healthy young persons, in whom percentage of T cells with СD45RO+, CD45RA+, CD4+СD45RO+, CD4+CD45RA+, CD8+СD45RO+, and CD8+CD45RA+ phenotypes was determined pre- and post-vaccination.

Following vaccination, increased average T cell levels of all the mentioned phenotypes was revealed in those volunteers who responded to the vaccine with elevated serum antibody titers. Individual data analysis has shown that, among individuals with antibody response, a percentage of persons with CD45RO+ T cells was 35 to 57%, as compared to vaccinated persons without such antibody response (11 to 22%, p < 0.05; p < 0.01). When using CD45RA+ marker, appropriate values among group 1 volunteers varied between 14 and 36%, whereas for group 2, only one case was detected with expression with significantly increased CD8+CD45RA+, expression on T cells post-vaccination.

Hence, a single immunization with live influenza vaccine is followed by significantly increased levels of peripheral CTLs (CD8+) and Th (СD4+) with СD45R0+ (memory cells) and СD45RА+ (naive) phenotypes in sufficient cohort of immunized persons (35 to 60%). Certain relations exist between post-vaccinal accumulation of memory T cells in peripheral blood, and development of a systemic humoral response to vaccination. However, this connection is not absolute, since an increase in these cells post-vaccination occurs in some persons without such a response (up to 25% of immunized individuals). (Med. Immunol., vol. 10, N 6, pp 535-542).

Abstract. We studied immunological state and activity of enzymes in blood lymphocytes from the patients at different stages of acute lymphoblastic leukemia. We have revealed that immune state in all the patients was characterized by decreased contents of T-lymphocytes. Upon first attack of the disease, they showed a decrease in CD4+cells, as well as increased concentration of IgM and IgG. During remission, we have found the lowest values of all the parameters under study. In relapsing patients, high content of NK-cells, and imbalance between the main Ig classes were noted. When studying metabolism of lymphocyte, it was revealed that, in first attack and relapse phase, both intensity of anaerobic glucose oxidation, and levels of macromolecular synthetic reactions were decreased. In remission, all these processes did recover to normal range. At all stages of disease, glutathione reductase activity was found to be decreased in blood lymphocytes. (Med. Immunol., vol. 10, N 6, pp 543-550).

Abstract. The issue of chronic adenoiditis, due to its medical and social significance, is in focus of attention for otolaryngologists, pediatricians, immunologists. According to various works, chronic adenoiditis in children comprise 20 to 56% of upper respiratory diseases. Chronic adenoiditis is characterized by relative resistance to conventional therapy, and, in pronounced cases, by low reversibility of pathological events. The studies performed have shown that the patients with chronic adenoiditis show some features of local and general immune deficiency that were exhibited as decreased serum IgA concentration and local sIgA secretion, as well as insufficient income of IgG from vascular system to the area of inflammation in patients with chronic adenoiditis. These local immune deficiencies were considered to be an indication for local immunotherapy. Dynamics of clinical symptoms and changes in immunoglobulin profile has shown that clinical efficiency of Imunofan therapy was dependent not solely on the initial clinical features of disease, but on the local immunity state. Analysis of initial immunoglobulin concentrations in nasopharyngeal lavage from the patients showing differential clinical response have demonstrated that therapeutic effect of Imunofan was most pronounced in the patients with initially moderate activity of inflammatory process, deficient IgG income from vascular system, decreased local IgA synthesis in the inflammatory foci. Certain clinical features of chronic adenoiditis, i.e., clinical course without hypertrophy of pharyngeal tonsils, local immune deficiency (decreased local IgA secretion and deficient IgG income from blood), with a background of moderate inflammatory events, may be used as a rationale for administration of local immunotherapy with Imunofan to these patients. (Med. Immunol., 2008, vol. 10, N 6, pp 551-562).

Abstract. An imbalance between pro- and anti-inflammatory cytokine synthesis plays a crucial role in pathogenesis of rheumatoid arthritis (RA), including erosive joint lesions. Differences in cytokine profiles of RA patients are sufficiently investigated. However, possible interrelations between cytokine profile, immune inflammation, RA progression, and the disease prognosis require further investigations. Due to active search for novel targets in anti-cytokine therapy of RA, evaluation of cytokine levels in peripheral blood and synovial joint fluid remain quite relevant. Therefore, novel methods aimed to determine mRNA expressed by cytokine genes are thought to be promising. Our research was intended to develop test systems for quantitative determination of mRNAs for the following cytokines: TNFα, IL-1β, IL-6, IL-8, IL-17, IL-15, IL-10, IFNγ, IL-4, IL-2. Present article concerns specificities of the developed test systems, description of their technical principles, as well as comparative studies of cytokine gene expression in peripheral blood and synovial joint fluid in RA patients. (Med. Immunol., 2008, vol. 10, N 6, pp 563-570).

Abstract. The aim of study was to compare the influence of lipopolysaccharide (LPS) component from Gram-negative bacteria (E. coli 055:B5), and a lysate of Gram-positive bacterium (Streptococcus pyogenes, type M1, strain 40/58) upon transendothelial migration rates of monocyte-like cells (THP-1 strain). Both LPS and lysate of Streptococcus pyogenes acted as chemoattractants for THP-1 cells. he studied components of Streptococcus pyogenes proved to be more active stimulants of transendothelial THP-1 cell migration, than LPS from E. coli. During spontaneous transmigration of THP-1 cells through a monolayer of endothelial cells, augmented levels of chemokines (RANTES, MCP-1, IL-8, IP-10) were noticed, that were more pronounced in presence of LPS. Upon spontaneous transmigration of THP-1 cells through endothelial monolayer, the levels of proinflammatory cytokines (TNFα, IL-1β and IL-6) in cultural medium were found to be rather low. The transmigration-associated secretion of these cytokines increased in presence of LPS and Streptococcus pyogenes lysate. Incubation with these bacterial constituents did increase cytokine levels both in monoculture of THP-1 cells and in transmigration model. Our results suggest that the levels of THP-1 transendothelial migration depend mainly on activation of monocyte-like cells influenced by PRR-ligands from Streptococcus pyogenes lysate. (Med. Immunol., vol. 10, N 6, pp 571-576).

Abstract. An experimental group of 45 nondescript white mice was selected for a study of the influence of systemic enzyme therapy on performance and ability to withstand intensive physical loads, as well as on production of main cytokines. The findings were compared to a control group of 45 mice who received placebo. The physical performance was assessed after 1, 2, and 3 weeks according to the length of test swimming in the aquarium with the attached load of 5% of the body mass. Findings indicate that systemic enzyme therapy led to increased performance and endurance with increased physical load in the experimental group after three weeks of therapy. The mice in the experimental group showed decreased levels of anti-inflammatory TNFα and IL - 1β. Other observed changes were within the error range. (Med. Immunol., vol. 10, N 6, pp 577-582).

Abstract. Thirty-seven children (7 to 14 years old) with chronic inflammatory lung diseases (ILD) were under study. It was revealed that the contents of T-lymphocytes with CD3+ and CD4+ markers, and B-lymphocytes (CD20+) were relatively decreased in the patients, but their absolute amounts proved to be increased, along with sufficiently decreased CD4+/CD8+ ratio, and diminished IgA, IgG and IgM concentrations. The numbers of lymphocyte able to adhere to platelets was relatively decreased, being, however, increased in absolute counts. In the patients with ILD, we have found increased levels of IL-1β, IL-8, TNFα, IFNα, IFNγ. The lymphocyte-to-platelet adherence is an objective test that reflects functional state of cell immunity. (Med. Immunol., vol. 10, N 6, pp 583-588).

Abstract. A complex immunologic examination of fifty patients with clinically significant postoperative fibrosis has been performed. Immunogram indexes were determined, and activities of basic oxidation-reduction enzymes were investigated in blood lymphocytes. What concerned immune status of the patients under study, some peculiar features have been revealed, with respect to cellular and humoral compartments, i.e., relative increase in CD3+ population, a shift to CD4+ cells in the ratio of lymphocyte subpopulations, higher indexes of immune regulation and phagocytosis, increased IgG level, and lower content of IgA, as compared to appropriate controls. Metabolic parameters of lymphocytes reflect their functional activation, being expressed as an enhanced ability for intracellular synthetic processes, elevated functional activity of lymphocytes, and increased immune response. The general pattern of changes in immune status and metabolic indexes of lymphocytes allow us to assume participation of autoimmune component in progression of epidural fibrosis. The data obtained may be used in combined diagnostics and correction of this disorder. (Med. Immunol., vol. 10, N 6, pp 589-592).

Abstract. Were researched IgG on the surface cells of different histological types tumors of cerebrum, using fluorescing staphylococcus A-protein. The study of target IgG shows divers intensive of microscopic fluorescent illumination. This results associate related with level amount IgG. The maximum concentrate of surface’s IgG was on the cells of malignant tumors and there was direct correlate with aggressive manner and quickly recurrence of tumor’s growth, and shot survival. The fraction of IgG with specific antitumor’s antibody covers tumor’s antigens has been block this antigens for receptors of T-lymphocytes. Linked with immunological anticell’s deficit phenomenon may be one from famous reasons of malignant clinical type tumor disease. (Med. Immunol., vol. 10, N 6, pp 593-596).