Bacterial DNA, along with other bacterial pathogen-associated molecular structures, may activate both innate and adaptive immune systems. This activity is associated with by nonmethylated CpG dinucleotides, which are present in the bDNA molecule, and it may be simulated by synthetic CpG oligodeoxynucleotides (ODNs). Non-methylated CpG motifs are recognized by Toll-like receptor 9 that triggers the induction of cell signaling pathways, activating proinflammatory cytokine synthesis by immune competent cells, and triggering the immune protection mechanisms. In present review we consider structure, functions, adjuvant features, immune properties and potential clinical applications of bacterial DNA and various classes of synthetic non-methylated CpG-ODNs.

he data presented in this review article characterize the key role of alterations in humoral and cellular immunity factors detectable during post-infarction period. According to these data, immune reactivity may define both a level of the myocardial lesion, and a subsequent clinical course of the disease. 

Present study has shown that a total cytokine pool produced by human blood cells in presence of proteins from the γ-globulin fraction, or their complexes with copper and zinc, as well as with pure copper and zinc cations, contains up to 148.0±14.9 pg interleukin-1β (IL-1β) per mL. The γ-globulins modified by copper or zinc binding induce, resp., 2.0 and 1.4-fold less IL-1β than intact proteins (significant by p = 0.1). Meanwhile, the copper-γ-globulin proved to be 2.7-fold more active (р < 0.01) IL-1β inducer, as a zinc-protein complex. Pure zinc ions did not induce IL-1β production, whereas induction rates with pure copper ions are 1.6-fold higher (p < 0.05) than with γ-globulin, and 1.45-fold more efficient that PHA stimulation (p < 0.1). A potential participation of copper and zinc cations bound to antibodies from the microenvironment and, thus, transforming Fc regions of antibody molecules, is discussed with regard of regulation of IL-1β production by human blood cells induced by activation of their Fc receptors.

Contact sensitivity is a classical T cell-mediated, clinically important phenomenon elicited by small molecular weight molecules (haptens) that bind to host proteins to form a complete antigen. In our model experiments, contact sensitivity was produced in CBA mice, by means of cutaneous sensitization with 2.4-dinitrofluorobenzene. We used an adoptive transfer of contact sensitivity with different populations of splenocytes, in order to detect immunosuppressive effects of licorice (Glycyrrhizae) root flavonoids. Suppression of adoptive transfer of contact sensitivity in mice-recipients to different degree was found, when applying the flavonoids. It was revealed, that this effect depends on the type of target population interacting with flavonoids. We have also demonstrate, that licorice root flavonoids do not induce apoptosis of effector cells.

The study deals with evaluation of immune parameters in healthy fertile women (n = 48) versus female patients with infertility of unknown origin (n = 386). A comparative analysis has shown similar patterns of immune dysfunction in women with primary infertility (n = 179) and recurrent spontaneous abortion (n = 207). The most common markers of immune dysfunction include decreased production of blocking antibodies (86.5% of cases), low proliferative response to paternal alloantigens in mixed leukocyte reaction (MLR) shown in 51.5% of cases, and increased number of activated CD56+CD16+NK-cells (42.0%). Decreased production of MLR-blocking antibodies may be caused by low lymphocyte response, due to the partner's HLA-similarity, or by predominance of Th1/proinflammatory cytokines and low contents of circulating regulatory CD4+CD25+T-cells. The study results demonstrate that development of primary infertility and recurrent spontaneous abortions is associated with a uniform set of immune disorders, thus probably reflecting a failure of suppressor rearrangement within immune system during periovulatory period of menstrual cycle.

The article presents data on the levels of transforming growth factor-beta-1 (TGF-β1) in blood serum and their correlation with clinical features of coronary artery disease in 130 patients with non-ST elevation acute coronary syndrome (non-ST ACS), who underwent coronary artery bypass grafting surgery (CABG), at different terms (6, 12, 24, 48 mo) following surgical intervention. It was revealed that a recurrent myocardial ischemia is associated with increased levels of TGF-β1. Following CABG, the TGF-β1 levels are significantly increasing, and reach their preoperative values by the end of observation period.

High incidence of accompanying somatic diseases has been revealed in patients with primary headache syndromes, while clinical manifestations of immune disorders being quite prevalent among them. The most common immune pathology in the studied patients were secondary immune deficiency and allergic diseases. Significant differences in the rates of chronic inflammatory and allergic diseases in patients with episodic and chronic primary headaches allow of considering these conditions as a factor unfavorably affecting clinical course of cephalalgias. The results of laboratory examinations in the studied patients showed presence of immune deficiency features, with changing ratio of immune subpopulations, altered functional activity of neutrophils, decreased IgG levels, and imbalance in cytokine system.

Antibodies to the cytoplasm of neutrophils (p-ANCA) are detectable in 67% of patients with ulcerative colitis (UC). We have revealed typical clinical features of the patients with diagnostic p-ANCA titer, i.e., longer disease duration, prolonged fevers, and increased stool frequency. Moreover, thrombocytosis, leukocytosis and hypoalbuminemia are more common in this group. By endoscopic examination, mucosal ulcers of the colon are significantly more frequent in this group of patients. We have also noted higher rates of severe and relapsing cases among p-ANCA-positive patients. The data obtained allow us to suggest that the diagnostic titers of p-ANCA are predictive for unfavorable prognosis in UC.

Fifty patients with primary "dry eye" syndrome underwent examination of systemic immunity including the determination of cell populations and subsets of CD3+, CD4+, CD8+, CD16+, CD20+ lymphocytes; measurements of major immunoglobulins: IgA, IgM, IgG; circulatory immune complexes (CIC); rheumatoid factor, antibodies to denatured and nondenatured DNA, and phagocytic index. When compared to relatively healthy subjects (n = 30), the patients, showed decreased contents of CD3+ and CD4+T-lymphocytes, increased IgM and CIC concentrations, along with presence of autoantibodies in blood. Moreover, some variable changes were revealed in the quantities of CD8+ cytotoxic T-lymphocytes, and the values of immunoregulatory index (IRI). As based on immunologic findings, with regard of CIC contents, autoantibody titers and IRI values, we have discerned four types of primary "dry eye" syndrome, i.e., simple, cytotoxic, CIC-positive, and Sjogren's syndrome. The changes of systemic immunity in the patients with different etiology of primary "dry eye" syndrome should be considered when elaborating therapeutic strategies and aiming for prophylaxis of immunologic disorders in such a cohort of patients.

The study involved 56 patients with chronic obstructive pulmonary disease (COPD), stage III-IV, 38 patients with severe bronchial asthma (BA), and 45 patients with a combination of COPD stage III-IV and bronchial asthma at exacerbation period. In all the patients, we have measured blood levels of pro-inflammatory (IL-6, IL -8, TNFα) and anti-inflammatory (IL-4) cytokines, amounts of cell adhesion molecules (ICAM- 1, VCAM-1), along with assessment of contractile myocardial functional disorders by means of Doppler echocardiography. Highest rates of pro-inflammatory cytokines and adhesion molecules were found in the group of patients with combined pathology, along with most significant signs of myocardial hypertrophy, both in right and left heart compartments, accompanied by a decrease in contractile myocardial function.

The article presents novel data concerning measurements of cytokine levels (IFNγ, IL-4, IL-6, IL-10, TNFβ, MCP-1), and cell adhesion molecules (sE-Selectin, sICAM-1) in blood plasma, llike as parameters of their diagnostic efficiency in the patients with thyroid autoimmune diseases (TAD), thyroid adenoma and cancer. The cytokines were analyzed by flow cytometris technique. We have shown that IL-4, IL-6, TNFβ, MCP-1 cytokines play an important role in pathogenesis of TAD, especially IL- 6, MCP-1. In cases of thyroid adenoma, a sufficient role belongs to IL-6, IL-10, TNFβ, MCP-1, sICAM-1, with IL-6 и sICAM-1 showing most significant changes. In thyroid cancer, IL-6, IL-10, MCP-1, sE-seleсtin are informative, with sE-seleсtin being the most reliable marker. In differential diagnostic between thyroid cancer and autoimmune diseases, one should employ such cytokines, as IL-10, MCP-1, sE-seleсtin, the latter being most significant. Differential diagnostics between thyroid adenoma and autoimmune diseases suggests determination of IL-6, IL-10 and sICAM-1 levels, preferring IL-6 and sICAM-1for their better diagnostic efficiency. Threshold levels of IL-6, sE-seleсtin may discriminate between thyroid cancer and adenoma, but these differences are of poor diagnostic efficiency.

Experimental autoimmune encephalomyelitis in an adoptive transfer model is caused by injecting animal with activated T cells specific for a CNS antigen, e.g., basic myelin protein. Development of autimmune inflammation in such a model is connected with changed functional stateof encephalytogenic (EG) T cells in the coure of disease progression, as reflected by changes in their activation, proliferation and motility levels. Present work describes an original technique allowing for in vitro analysis of encephalytogenic T cell motility, and studying effects of certain compomemts of extracellular matrix upon migration and functional activities of EG T cells.

Present lecture contains an author's opinion concerning diagnostic issues in immunopathology, including primary and secondary immune deficiencies, immune-dependent states that are based on immunopathological syndromes. Original formulations are suggested for some key categories of clinical immunology, physical, instrumental and laboratory diagnostics of immune deficiencies and immune-dependent diseases. The results of original long-term observations, as well as data on Sverdlovsk Regional Register of primary immune deficiencies are presented in the work.