Abstract. T-lymphocytes play an important role in elimination of tumor cells, in reactions of a transplant against graft and graft versus host disease, in slow-type hypersensitivity, and other reactions directed for maintenance of homeostasis. Along with CD3, an antigen-specific T-cellular receptor (TCR) is another common marker of T-cells. There are two types of TcR – αβ-TcR and γδ-TcR that differ in ontogenetic and functional properties. γδ-T-cells play a significant role in protection of organism against various types of infections, and determination of their amounts should be an integral part of the analysis of patients’ immune status. To these purposes, a multi-colour analysis shuld be used, applying the following combinations of monoclonal antibodies: CD3/CD4/CD8/CD45 and αβ-TcR/γδ-TcR/CD3/CD45. Multi-colour staining and multi-step gating allow of carrying out multiparametric analysis of peripheral blood with high accuracy and reliability. The proposed approach considerably facilitates interpretation of results obtained, and it allows of judging about immune system functioning in various pathological conditions.

Abstract. In present review, the data are considered that concern a role of immunological mechanisms controlling the events of apoptosis at different stages of development of placenta. Intensity of apoptotic process in human placenta is progressively increasing in the course of pregnancy, until delivery act. The processes of apoptosis induction and its prevention in placental cells are inseparably linked to development of placenta and formation of vascular system, as controlled by trophoblast cells, as well as by maternal fetal immune cells. T-lymphocytes, natural killer cells, NKT-cells and macrophages that perform surveillance over the processes of angiogenesis and apoptosis in placental tissue, thus providing its normal development and functioning.

Abstract. Bronchial asthma is a classic psychosomatic disease by immunopathological origin. In present investigation, we studied influence of body-oriented psychotherapeutic methods directed towards clinico-immunological parameters and special psychological features of the patients with bronchial asthma, i.e., decrease in alexithymia, as an important pathogenetic factor of bronchial asthma, and improvement in motor coordination and interhemispheric interactions in motor sphere. We investigated 38 patients (18 men and 20 women), while discriminating those patients who underwent a course of body-oriented psychotherapy, and a group of comparison, who did not undergo similar therapy. When observing conventional standards of randomization according to sex, age, clinical variants, and disease severity, some heterogeneity of these groups was revealed. In general, the people with active life attitude, being ready to work with a psychologist, possessed special features both in psychological and immunological spheres.

Abstract. The study concerns phagocytic activity of neutrophilic granulocytes investigated in diabetic patients with insular diabetes, accompanied by maxillary sinusitis. The patients exhibited suppressed phagocytic abilities of neutrophilic granulocytes and monocytes, disturbed killing of captured bacteria, suppression of oxidase microbicidal system, and disorders of receptor system.

Abstract. Some functional properties of IFNα-induced dendritic cells (DCs) from the patients with pulmonary tuberculosis (PT) were under study. It was revealed that production of IFNγ and IFNα by DCs of the patients was decreased, but TNFα production was preserved at normal level. NO production by DCs from the patients was also reduced. In addition, it has been shown, that DCs of PT patients were characterized by low allostimulatory activity in mixed lymphocyte reaction (MLR), and this defect was more marked in the patients with PPD-anergy. As compared to healthy donors, DCs from the patients with PT (in particular, with PPD-anergy) exhibited a decreased capacity for induction of intracellular expression and production of IFNγ by T-cells. However, DCs from the patients with PPD-anergy were able to stimulate intracellular expression of IL-4 in CD3+T-cell subset. Hence, the results suggest that functional activity of DCs in the patients with PT is altered, and some of these changes are distinctly associated with decreased antigen-specific response. (Med. Immunol., 2008, vol. 10, N 2-3, pp 151-158).

Abstract. Percentage of CD4+CD25hi is increased in children with allergy, and it is independent on their nosology, severity, sensitization and IgE level in blood. FOXP3 expression virtually was not altered. Inhalation of corticosteroids in asthma causes increase of FOXP3 expression that may represent some mechanisms of their therapeutic effects. The amount of Treg’s gradually decrease with age in non-atopic children; they also decrease in atopic ones until 6 years, followed by their subsequent stabilization. Thus, a hypothesis is proposed, that the initial changes of Treg’s in case of allergy comprise a reduction in their functions, and, upon complete or partial compensation of this defect by increasing of cell amounts, a remission is initiated. However, in absence of compensation, acute attacks of allergic disorders are developed. (Med. Immunol., 2008, vol. 10, N 2-3, pp 159-166).

Abstract. Pathogenesis of reactive arthritis (ReA) is not clear yet. Several trials suggest that increased production of proinflammatory cytokines is responsible for development of arthritis in ReA, while other studies report that Th1 cytokine response in ReA is impaired in favor of Th2 response. The aim of our study was to investigate serum levels of cytokines IL-1β, IL-4, IL-6, TNFα, IFNγ and IL-1Ra in the patients with ReA of different etiology, as compared with infection-related arthritis. The results of our study had demonstrated that serum levels of IL-1β and TNFα in the patients with ReA were significantly higher, whereas IL-1Ra, IL-4, IL-6 proved to be significantly lower than in healthy controls. Serum levels of IL-6 were significantly higher in patients with chronic ReA, as compared to the cases of acute and recurrent ReA. No significant differences in cytokine profiles were found between the patients with ReA, and the persons with infection-related arthritis. The data obtained are, generally, suggestive for proinflammatory Th1 cytokine profile in ReA patients studied, this confirming the mostly assumed pathogenetic hypothesis for reactive arthritis where an underlying cytokine imbalance is suggested. (Med. Immunol., 2008, vol. 10, N 2-3, pp 167-172).

Abstract. The aim of present study was to evaluate efficacy of generation and characterization of regulatory T cells (Treg). The Treg were derived from peripheral mononuclear cells of healthy donors, using activation with anti-CD3mAb and IL-2, either in absence (model 1), or in the presence of immunosuppressive agents (vitamin D3 and dexamethasone, model 2). It was shown, that the Treg, obtained in model 1, are characterized by decreased anti-CD3-induced proliferative response and lack of suppressive activity. Treg, obtained in presence of vitamin D3 and dexamethasone, proved to be profoundly anergic. Such a state may be partially abolished by exogenic IL-2. These cells are also characterized by suppressive activity mediated by both cell-to-cell contacts and soluble factors, such as IL-10. Hence, the regulatory T cells generated in model 2, can be referred as inducible Treg (Tr1). Nevertheless, increased ratio of cells expressing CD4+FOXP3+ among Treg obtained by model 2, may also suggest an ability to generate natural regulatory cells. (Med. Immunol., 2008, vol. 10, n 2-3, pp 173-180).

Abstract. The contents of peripheral blood cells expressing activation markers are increased in patients with gastrointestinal malignancies, mostly in cases of gastric cancer. An association is revealed between the immunological parameters and histopathological features. Absolute contents of lymphocytes with CD71+ and HLA-DR+ phenotype, showing a significantly correlation with most pathological parameters of gastric tumors, may be considered as an informative marker of tumor progression at pre-surgical step. (Med. Immunol., 2008, vol. 10, N 2-3, pp 181-186).

Abstract. This article presents results of apoptosis detection among blood lymphocytes from the patients with autoimmune thyroid disorders, i.e., autoimmune thyroiditis (AIT) at euthyroid and hypothyroid stages, and in diffuse toxic goiter (DTG). Contents of CD95+, annexin V­ presenting (apoptotic) cells and TNFα in blood were analyzed. It was shown, that altered regulation of programmed lymphocyte death in autoimmune thyroid disorders is demonstrated by increased content of TNFα and CD95+ lymphocytes, being accompanied by decreased numbers of apoptotic cells in blood. Meanwhile, this pathology is expressed mostly in DTG, while being less significant in AIT at euthyroid stage, than in thyroid hypofunction. Possible mechanisms of the revealed disturbances are discussed. (Med. Immunol., 2008, vol. 10, N 2-3, pp 187-192).

Abstract. Experimental allergic encephalomyelitis (EAE) represents an inflammatory demyelinating CNS disease, thus being regarded as an experimental model of multiple sclerosis. The aim of present work was to study production of pro- and anti-inflammatory cytokines, and their expression in spinal cord of rats challenged with encephalitis-inducing mixture, in the course of EAE progression. Pathological features of EAE were characterized by meningeal, perivascular, and periventricular infiltration of brain stem, cerebellum and spinal cord. The areas of demyelinization were associated with inflammatory foci, being located at the edges of infiltrates. In sensitized animals, increased levels of serum ТNFα were detectable, being higher in diseased animals, as compared with healthy ones, both in latent phase and during advanced neurological disorder. Increase in circulating IL-10 was in parallel with initial phase of EAE, being also observed in recovering animals. Early increase of IL-10 levels predetermined mild course of the disease, accompanied by decrease in ТNFα activity, whereas low IL-10 levels were registered in severely ill rats with high ТNFα, followed by lethal outcome. ТNFα-specific mRNA was revealed in acute phase of EAE, IL-10 mRNA was detectable at the time of recovery. ТNFα expression was observed for a long time in cases of protracted disease, being, however, absent in EAE-free rats. The data demonstrate that higher levels of ТNFα in blood serum during latent period, and, especially, at later time, may promote development of damage in central nervous system. The central cytokine pool is involved into progression of neurological disorders, thus influencing duration and severity of the disease. (Med. Immunol., 2008, vol. 10, N 2-3, pp 193-202).

Abstract. Spearman rank correlation analysis was applied to assess some interrelations between morphological abnormalities of spermatozoids in males with long-term infertility, and cytokine levels in their seminal plasma. Such statistical analysis has revealed a significant positive correlation between prevalence of morphologically abnormal spermatozoids and the levels of IL-1β, MIP-1β, G-CSF, along with negative relationship with IL-5 and IL-10 contents in seminal fluid. The data are, generally, demonstrating participation of cytokines in regulation of male fertility. (Med. Immunol., 2008, Vol. 10, N 2-3, pp 203-208).

Abstract. Samples of renal cell carcinoma (RCC) and adjacent normal tissues were studied by means of immunoblotting, using monoclonal antibodies [(MKA 1, 1F3-2D4, IgG1 class), MKA 2H6, IgG1 class] against membrane proteins of HEp-2 cells (larynx cancer). Strong reactivity of MKA 1 was revealed with p34-38 (13/34, 38%) and p28-29 (7/34, 21%), and, generally, for 20 of 34 tumor samples(59%, p<0,05). The differences in antigen expression in renal cell carcinomas are statistically significant, as compared with adjacent (presumably normal) tissues. The p34-38 expression was not revealed in serum pellets obtained from 4 cancer patients by ultracentrifugation. A variety of multiple proteins was revealed in one оf seventeen tissue samples surrounding the tumor (normal breast tissue). Interestingly, a difference was found between renal cell carcinoma (p28-29 expression) and adjacent normal tissues (p21-24) that was revealed by means of MKA 2H6. The p21-24 and p28-29 may represent a product of p34-38 posttranslational modifications. It was supposed that a variety of proteins revealed with MKA 1, 2H6 are interrelated, due to identity of some sites. Detection of p34-38, p28-29 with MKA 1 may be potentially used as a supplementary immunological approach, in order to differentiate renal cell carcinoma tissues of epithelial origin from the adjacent tissues. Further studies are needed to elucidate an opportunity of MKA 2H6 usage, aiming for detection of p28-29 in renal cell carcinoma samples, like as p21-24 for specimens of adjacent normal tissues. (Med. Immunol., 2008, vol. 10, N 2-3, pp 209-214).

Abstract. Design of an effective and safe vaccine against pathogenic streptococci is still on the agenda, in spite of numerous attempts in this area undertaken by different laboratories. In order to improve immunogenicity of recombinant vaccine preparations, a selection of effective adjuvants is necessary. Previously, two recombinant GBS polypeptides P6 and ScaAB were found to be immunogenic, and their injection in separate preparations or mixed manner boosted production of specific and protective antibodies with high affinity. Four different adjuvants (Freund adjuvant, aluminum hydroxide, Bestim and Interleukine-1β) have been tested for immunization of mice with single polypeptides, or with their mixtures. As a result of vaccination, it was demonstrated that aluminum hydroxide was providing the most desirable immunological parameters of immune response among the adjuvants tested. A mixture of polypeptides containing aluminum hydroxide was found to produce specific antibodies with better opsonizing activity against group B streptococci. (Med. Immunol., 2008, vol. 10, N 2-3, pp 215-222).

Abstract. One hundred and ninety-nine patients with hyperplastic processes of reproductive system were examined, and 131 (66.16%) of them were found to be infected with Chlamydia or Ureaplasma. The mean age of female patients was 42,7±1,35 years. Different infectious agents (e.g. Chlamydia trachomatis, Ureaplasma urealiticum, Mycoplasma hominis) were identified in cervical canal of uterine cervix and surgical specimens (biopsy samples of excised myoma, adenomyosis or endometrial hyperplasia). The infected patients were found to have decreased monocytes and neutrophils in blood counts, lower phagocytic activity of monocytes and neutrophils, and decreased bactericidal activity of leukocytes. Other findings included lower CD20+, CD8+ and rFAS CD 95 lymphocytes. Assessment of cytokine-synthesizing activity of CD3+ lymphocytes showed a decrease in both spontaneous and stimulated response (р < 0,001). A weakest spontaneous and stimulated response was found in CD3+/IL-4+ lymphocytes. Analysis of results obtained shows systemic immune disorders and impaired cytokine-synthesizing activity of CD3+ lymphocytes correlating with infection factors in the women with hyperplastic processes of reproductive system. (Med. Immunol., 2008, vol. 10, N 2-3, pp 223-228).

Abstract. The aim of this study was to detect some features of autoreactive IgM production that interact with IgGs and normal human cellular antigens in blood sera of patients with acute respiratory viral infections caused by various factors, dependent on their age and clinical features of disease. The antibody concentrations were determined by immunoenzyme technique in paired serum samples from 750 patients and single specimens from 97 healthy persons. The results of analysis have shown that the studied types of autoreactive IgM represent a normal component of humoral immunity, since they are detectable in sufficient number of normal sera from healthy persons over 3 years old. In acute respiratory viral infections of different etiology, the rates of appropriate seroconversions comprised 0 to 16% for age cohort of < 3 years old. Incidence of seroconversions reached 37% among older children and adult patients with respiratory syncitial virus (RSV), or adenoviral infection, thus being 1.7 to 5.1-fold higher than in patients with influenza A, or B, or parainfluenza. In cases of clinical complications of RSV or parainfluenza infections (i.e., respiratory tract obstruction, or pneumonia), the rates of seroconversions to autoreactive IgMs was 1.4 to1.8-fold higher than among the patients with uncomplicated clinical course of these infections. (Med. Immunol., 2008, vol. 10, N 2-3, pp 229-238).

Abstract. Examination of immunomodulatory actions and clinical efficiency of myelopidum when included into complex therapy that was carried out in 24 male patients with severe (stage 3) penetrating eye injury in the course of trauma treatment. The levels of C-reactive protein, lactoferrin, interleukin (IL)-1β, IL-6, and activity of complement system were measured in peripheral blood, and concentrations of lactoferrin and IL-8 were determined in tears. An increase in lactoferrin, C-reactive protein, IL-1β, IL-8, and C5 complement component levels was detected during early post-traumatic period, as compared with data from the control group. As compared to effects of steroid and non-steroid anti-inflammatory drugs included into standard therapy, treatment with myelopidum has led to a more favorable clinical course of traumatic process, and resulted into more pronounced anti-inflammatory effect that was manifested by decrease in lactoferrin and C-reactive protein levels, reduction of IL-1β concentration, and C5 complement component activity. (Med. Immunol., 2008, vol. 10, N 2-3, pp 239-244).

Abstract. Role of cytokines in autoimmune reactions in Graves–Basedow disease (GBD) is undisputable. It has been shown, that dynamic alterations in serum Th1 and Th2 marker cytokines are dependent on disease stage. At initial phase of autoimmune thyrotoxicosis, the maximal values were shown for IL-1α, IL-8, IFNγ and IL-10. A direct correlation is proven between the degree of disease severity, and the levels of proinflammatory (IL-1α, IL-8, IFNγ), as well as anti-inflammatory cytokines (IL-10), like as with production of antibodies against thyroid receptors. During conventional treatment with standard doses of thiamazol, the levels of cytokines are significantly decreased. These data extend our knowledge on pathogenetic mechanisms of the disorder. Moreover, they allow of developing an algorithm for assessment of therapeutic efficiency and probability of relapses in autoimmune thyrotoxicosis. (Med. Immunol., 2008, vol. 10, N 2-3, pp 245-250).

Abstract. Rheumatoid arthritis (RA) is a chronic autoimmune systemic disease with predominantly destructive lesions of peripheral joints, with prevalence of 0.6 to 1.6% in general population. An important pathogenetic role in this disease is now attributed to imbalance between pro- and antiinflammatory cytokines. Clinical introduction of biological preparations, such as Infliximab (monoclonal antibodies to TNFα) within last years have changed therapeutic approach to treatment of rheumatic diseases. The aim of our research was to evaluate dynamics of pro- and antiinflammatory cytokine profile in the patients with rheumatoid arthritis (RА) during combined therapy with Infliximab and Methotrexate (MT). The study included 30 patients (27 females, 3 males, mean age of 52.5±2.0 years) who received combined therapy with МТ and Infliximab (Inx). Inx was initially injected at a single dose of 3 mg/kg intravenously, followed by administration 2 and 6 weeks later, and then repeated every 8 weeks. Regular examination of the patients included clinical and laboratory studies (ESR, levels of IL-6, IL-8, TNFα, IL-4, IL-10, GSM-CSF, IFNγ). Levels of antibodies against Infliximab in the groups of RА patients were determined before treatment and 22 weeks later. Efficiency of the therapy was estimated according to DAS28 3V Index and to HAQ Questionnaire.

Upon decreased activity of disease, as assessed by DAS28, and improvement of HAQ parameters, a marked decrease in proinflammatory cytokine levels (IL-6, IL-8, TNFα) was detected, that confirming a pathogenetic significance of cytokine in RА patients. In patients with marked clinical effect (group I), an initially normal contents of TNFα was found in blood serum, and this group showed better response to Infliximab therapy, than groups II and III (resp., moderate and absent response) with initially high contents of TNFα and other cytokines, that was proven by correlations with ACR criteria and HAQ functional index. These events were accompanied by more significant improvement of RА course and increased functional abilities of joints. In patients from group III (absence of clinical effects), the level of antibodies to Infliximab before therapy was high, and it was increased by 22 week of treatment. It was shown that, in cases of initially high levels of endogenous anti-TNFα antibodies, clinical response to Infliximab therapy is likely to be reduced. Thus, it is possible to suggest that determination of initial TNFα and IL-10 levels, as well as starting levels of antibodies to Infliximab, and their changes in the course of therapy can be used as immunological parameters, thus allowing to predict the responses to Infliximab therapy. (Med. Immunol., 2008, vol. 10, N 2-3, pp 251-260).

Abstract. Since decades, the aspects of chronic adenoiditis draw attention of specialists in ORL. From different data, prevalence of chronic adenoiditis is 20 to 56 per cent among children with diseases of upper respiratory ways. Chronic adenoiditis is relatively resistant to conventional therapy, and irreversible clinical course is revealed in more severe cases. The studies performed have shown that the patients with chronic adenoiditis exhibit signs of local immune deficiency that manifested into decreased local secretion of IL-4, IL-10 and GM-CSF, thus being considered as an indication for local immunocorrection procedures. To this purpose, we used Imunophan as a spray for intranasal application. Dynamics of clinical symptoms and local immune parameters showed that the efficiency of Imunophan treatment was dependent of both initial clinical features of the disorder, and on cytokine levels in oropharyngeal lavages. Therapeutic effect of Imunophan was more expressed in the patients with initial predomination of Th1 immune response and cell-type immune reactions in the area of inflammation. A set of certain clinical and laboratory data, i.e., absence of enlarged pharyngeal glands, predominance of local Th1 type response and cellular type of immune response may be used for monitoring before administration of local immunotherapy with Imunophan in the patients with chronic adenoiditis. (Med. Immunol., 2008, vol. 10, N 2-3, pp 261-268).

Abstract. A study of immunotropic properties of ω-(3,5-dimethyl-4-hydroxyphenyl) propylthiosulfonate, sodium salt (F-11-7), and ω-(3,5-di-tret-butil-4-hydroxyphenyl) propylthiosulfonate, sodium salt (F-17-7) was carried out, employing an in vitro model of spontaneous and mitogen- stimulated proliferation of cultured spleen cells. It is revealed, that the F-11-7 and F-17-7 compounds are able to suppress proliferation of intact splenocytes in a dose-dependent manner. (Med. Immunol., 2008, vol. 10, n 2-3, pp 269-272).

Abstract. A group of 122 children, aged 7 to 16 year, with minor clinical forms of tuberculosis and infected with Toxoplasma gondii (T. gondii) and Epstein–Barr virus (EBV) was examined to evaluate the cytokine system. Immunoenzyme techniques were used to detect the presence IgM, IgA, IgG to T. gondii and EBV, as well as IL-1β, IL-1Ra, IL-4, IL-8, and IFNγ cytokines in blood. The patients were classified into three groups: (I) children with IgG to T. gondii, (II) children with IgM or IgA to T. gondii (active toxoplasmosis), (III) children with T. gondii-specific IgA and EBV-IgG-EA (active course of both toxoplasmosis and EBV infection). A comparison group (IV) consisted of TB-infected, T. gondii-seronegative patients without EBV-IgG-EA. A control group included thirty persons without evident disease. In groups I-III, a simultaneous and significant increase in IL-4 and spontaneous IFNγ contents was found, in comparison with controls. In group III, however, a 4-fold depression in IL-1β production was revealed against group IV, along with a 5.5-fold stimulation IFNγ production (as compared with controls). In groups I, II, IV, an inadequate hyperproduction of IL-1β and low IL-1Ra levels were shown. In the group III, a 3.4-fold and 5,5 fold IL-1Ra decrease were found, as compared, respectively, with group IV and control group. IL-8 content in groups I to III significantly exceeded control values (a 2.9 to 3-fold increase, with higher rates in group II). Hence, a direct inhibitory effect of EBV upon cell-mediated immunity should not be excluded under the conditions of TB-infection and active toxoplasmosis, thus further aggravating the immune dysfunction. (Med.Immunol., 2008, vol. 10, N 2-3, pp 273-276).

Abstract. We performed a clinical and immunological study of patients from senior age group suffering with protracted purulent inflammation of soft tissues in maxillo-facial area. The patients underwent either common medication, or combined treatment including ozone therapy. Application of medicinal ozone, along with basic treatment schedule, resulted into more marked and rapid normalization of non-specific resistance markers, Т-cell immunity. This approach allows of reducing the terms of inpatient care and variety of possible complications. (Med. Immunol., 2008, vol. 10, N 2-3, pp 277-282).

Abstract. Patients with exacerbation of chronic herpesvirus infection were subjected to immunocorrection therapy. In the course of treatment, time-dependent correlations were found between the changes in production of IFNγ, IL-1β and IL-6, and initial level of IFNγ. The patients with high initial concentrations of IFNγ did also exhibit above-normal initial IL-1Β and IL-6 values, as compared to appropriate parameters for a sub-group with low IFNγ levels. In the course of immunocorrection with Echinacea, all the patients showed increase in IFNγ levels. However, due to initially low IFNγ values, its increase was more pronounced than in persons with high background levels of IFNγ. Dynamics of IL-1Β decrease and changes in IL-6 concentrations were more expressed in cases of higher initial levels of these cytokines. The alterations revealed for IFNγ, IL-1Β and IL-6 levels confirm that immunocorrection with Echinacea causes reduced intensity of inflammation and activation of antiviral immune response. (Med. Immunol., 2008, vol. 10, N 2-3, pp 283-290).