Numerous literature data indicate to gradual, but steady ageependent decrease of immunological reactivity in human organism, manifesting as a reduced ability to develop specific immune response, both of cellular and humoral type. Such negative trends result into increased proposition and frequency of various diseases, including cancer and autoimmune disorders. Finally, an age-associated immunodeficiency is developed even in normal organism, without clear background of specific disorders. The multicomponent mechanisms of such deficiency are not yet fully clarified. One may assume that, among these potentially leading mechanisms, a homeostatic proliferation may be of sufficient importance. This type of cell growth is shown to accompany any negative effects on the numbers of lymphocytes in the body. It manifests as a reduced ability of lymphocytes to recognize foreign antigens associated with a background increase of self-reactive cells.

In this review article, we present current clinical data about the effects of transfused hemocomponents upon immune system of the recipients, and about transfusion-related immunomodulation, with emphasis on the role of T-regulatory (Treg) cells in these events. The article describes a role of Treg’s in development of tolerance to self-antigens, in decrease of anti-neoplastic and anti-infection immune response, and their proposed role in transfusion-related immunomodulatory effects.

This study describes a design of genetic constructs encoding either non-specific, or HLA-A *0201-specific polyepitopic immunogens containing antigenic determinants for HER2 protein. We have shown that transfection of mature dendritic cells by polyepitopic constructs with magnetic nanoparticles lead to effective in vitro stimulation of cytotoxic immune response of mononuclear cell populations obtained from HLA-A0201-positive healthy donors/ This cytotoxic action was assessed in vitro, as lethal effects upon HLA-A0201/HER2 double positive MCF-7 tumor cells, and expression of perforin granules.

Two-hundred-eleven patients 3 to 14 years old (mean age 8.60±0.22 years) were observed and clinically evaluated at the Department of Pediatric Phthisiopulmonology, St.Petersburg Institute of Phthisiopulmonology during 2011-2013. The diagnostic protocol included: clinical data, X-rays diagnostics and immunologic assessment. All the patients were examined by DIASKINTEST® (DST) and QuantiferonTB Gold (QFT-G). They were divided into 2 groups, as based on laboratory data, as follows: group I (n= 63), patients with negative DST and QFT-G results; group II (n = 148), with positive results of specific tests. The study was aimed for intergroup comparisons of immune response markers. Positive results of DST and QFT-G suggested clinical activity of tuberculosis infection and are associated with high scores of tuberculin skin test (TST); increased cytokine levels (TNFα, IL-2, IFNγ), higher percentage of CD3+, CD4+ и CD95+ cells, elevated levels of specific IgG antibodies (anda TB ELISA); high titers of complement fixation test for mycobacteria, and activation of neutrophils. Positive results of DST and QFT-G in the patients are more often associated with active infection.

Previous studies with some solid tumors has shown that polymorphisms of certain cytokine genes may be used as predictors of clinical outcome in the patients. It seemed important to evaluate potential correlations between production of certain pro- and anti-inflammatory cytokines and co-receptor molecules, and promoter polymorphism of the cytokine genes involved into regulation of cell proliferation, differentiation, apoptosis, lipid metabolism and blood clotting in the patients with hematological malignancies. The article contains our results concerning associations between of IL-1β, -2, -4, -10, -17, TNFα, and allelic polymorphisms of their genes in 62 patients with B cell lymphoid malignancies in an ethnically homogenous group (self-identified as Russians. We have shown that the GА and AA genotypes of the G-308A polymorphism in TNFα gene are significantly associated with increased production of this cytokine, being more common in aggressive non-Hodgkin lymphomas, more rare in multiple myeloma and in indolent non-Hodgkin lymphomas.

We have conducted a study of a novel monoclonal A3 antibody raised by means of hybridoma biotechnology. The study was performed with malignant cells of the patients with various lymphoproliferative disorders, and persons with nonmalignant diseases, as compared with intact lymphocytes from healthy people,
using a method of immunocytochemical staining and indirect immunofluorescence technique. It was found that in cases of lymphoproliferative diseases with low proliferation rates, as based on the numbers of Ki-67 positive cells, as well as in non-malignant blood diseases, the A3 antigen was localized in nucleoli, and it was visualized as focal fluorescence. In malignant lymphoproliferative diseases with high proliferation indexes, the number of brightly fluorescent foci is observed, with formation of necklace-like structures within the nucleolar structures. The obtained data point to a diagnostic significance of A3 Mab in assessment of cellular proliferative rates in patients with various lymphoproliferative diseases. It was established that, in contrast to Ki-67, the proliferation stage could be determined for each cell, according to the number of fuorescent foci in nucleoli. This specific property of the A3 antigen points to its significance for diagnostics and malignancy staging of lymphoproliferative disorders.

Treatment of malignant tumors is among challenging issues of clinical medicine. Dissemination and matestasis of tumor cells plays a major role in oncology, being immediately dependent on chemotaxis of tumor cells. Hence, the aim of our study is to evaluate migration of tumor cells, in terms of ligand-mediated chemotaxis of a human U 937 lymphoma cell line. Synthetic TLR ligands (DNA_lig, RNA_lig) were used as chemoattractants. Assessment of time-dependent TLR expression by the migrating cells (including TLR2, TLR3, TLR7, TLR9) was carried out by means of real-time PCR, using Boyden’s chamber system for the migration assays. We have revealed an increased cell migration towards DNA_ lig and TNFα gradient. Expression of TLR2, TLR7 and TLR9 was found to be increased under the influence of TNFα (respectively 1.5-, 4- and 19-fold). Under the influence of DNA_lig, TLR9 expression was 105-fold increased, whereas TLR3 expression was 2-fold higher, along with decrease of TLR2 expression. Expression of TLR 3 was shown to be 3-times higher under the influence of RNA_lig. The effects observed could be potentially applied for suppression of tumor cell chemotaxis by means of these ligands and by influencing different pathways of
chemotaxis regulation.

Phenotyping of peripheral blood lymphocytes and immune activation markers of activation (HLADR, CD38, CD69, CD314, CD25) was performed in thirteen patients with disseminated forms of stomach and rectal cancer before cell treatment, and following adoptive immunotherapy with activated lymphocytes. It was
shown that the lymphocytes are well activated and are able to proliferate in vitro. It was revealed that the relative content of Tregs and NK cells is increased in these patients. After the courses of immunotherapy, initially low levels of B-cells (average 5%) remained in all the patients, whereas concentration of Тregs didn’t change. Increased expression of activation markers was revealed for all lymphocyte subsets (CD25, CD314, CD38, HLA-DR) and, especially, for T-lymphocytes (CD3+HLA-DR, CD3+CD38+). Significant decrease of T helpers, activated NK-cells (CD16+CD314+) and CD4+/CD8+ was noted in peripheral blood. A non-significant elevation in mature lymphocytes (CD45RO+) and reduced content of young lymphocytes (CD45RA+) were revealed. Adoptive immunotherapy is safe and well tolerated, being characterized by lack of side effects, and it may be recommended as a complement to conventional radio- and chemotherapy.

Patterns of immune response, cytokine- and NO-ergic mechanisms and their role in the development of basal-cell skin cancer were evaluated in population of an industrialized region. Multiple forms of basal-cell skin cancer and primary multiple cancer were characterized by the evidence of Th2-dependent imbalance of immune response, decreased cytolytic potential, increase of EGF, TGF-β, IL-1β, IL-4, IFNγ, lactoferrin levels, thus suggesting a particular immune defense strategy in malignant growth.

Level of serum secretory immunoglobulin A was investigated in alcoholic liver disease (ALD, 59 men and 23 women) and non-alcoholic fatty liver disease (NAFLD, 17 men and 93 women).The data were compared with those of persons without liver pathology (control group, 43 men and 73 women). Moreover, we studied possible associations between ssIgA level and Gln223Arg polymorphism of the LEPR gene. Immunological and DNA diagnostics was performed by means of, respectively, ELISA and allele-specific polymerase chain reaction. We have found that the average level of ssIgA was three times higher in ALD group (11.45±0.82 mg/l), than in the NAFLD group (4.35±0.35 mg/l) or in controls (3,60±0,29 mg/l). SsIgА concentration did not depend on adiposity and gender. The ssIgА concentration proved to be increased in Gln223Arg heterozygotes with NAFLD, when compared with controls. However, the frequency of 223Arg and 223Gln alleles was virtually equal in all observed groups with above-normal concentration of ssIgА, as compared to a sub-group with normal ssIgА concentration. Hence, we have not revealed any significant association between Gln223Arg polymorphism of LEPR and ssIgA level. The data obtained will be useful for studying genetic risk factors in development of infectious mucosаl lesions.

The issues of cytokine activation in patients with ischemic heart disease (IHD) are widely discussed in medical literature, including both chronic and acute clinical course of the disorder. However, appropriate changes still remain unclear. E.g., attention in research is drawn to possible role of melatonin (MT), an epiphysis hormone. The available findings on MT production in acute forms of IHD are controversial. We have determined blood levels of IL-6 and IL-10 in 98 patients with IHD, of them 93 suffering from acute coronary syndrome (ACS), and 5, with stable angina pectoris (SAP), functional class II-III, and evaluated their correlation with urinary contents of the MT metabolite (6–hydroxymelatonin, 6-HOMT). ACS patients, when compared with SAP patients, showed an increase of IL-6 and IL-10 levels, whereas 6-HOMT contents were found to be decreased. In the patients with unstable angina pectoris and non-Q myocardial infarction (IM), we have revealed more elevated values of IL-6 and IL-10, as well as 6-HOMT. IL-6 and IL-10 levels appeared to be higher and those of 6-HOMT proved to be lower in patients with a history of anterior IM. The levels of 6-HOMT were found to be significantly increased in the patients with complicated IM. The levels of IL-6 and IL-10 in blood and 6-HOMT in urine can be used as auxiliary diagnostic criteria, in order to predict possible development of cardiovascular complications during ACS during hospital period.

The aim of this study was to assess effects of the eight-week course of atorvastatin therapy upon the levels of spontaneous cytokine production by mononuclear blood leukocytes (MNBC) in metabolic syndrome. An open-label prospective study included 36 patients with stage II hypertension (blood pressure < 180/110 mm Hg.) accomplished by metabolic syndrome. Along with clinical surveys performed at a specialized cardiological clinics, we assessed spontaneous cytokine production by MNBC during treatment with atorvastatin. It was shown that the 8-week treatment of these patients with atorvaststin, at individually matched daily doses (20
to 40 mg) was associated with reduced serum concentration of acute phase proteins (C-reactive protein and neopterin), as well as decreased spontaneous production of proinflammatory cytokines (IL-1β, IL-6 and TNFα) by MNBCs. The latter finding is of great importance for pathogenesis of metabolic syndrome.