Russian journal of immunology : RJI : official journal of Russian Society of Immunology最新文献

This article reviews recent achievements in molecular immunology that have given a new insight into the mechanisms of tumor escape from the control of immunocompetent cells and opened the way to the development of radically new immunotherapeutic procedures and further improvement of existing chemotherapeutic techniques. The application of new updated techniques in molecular biology, biochemistry and cellular biotechnology has made it possible to detect molecular changes in tumor cells which help to escape them from immunological control and develop on their basis some novel approaches to immunotherapy of malignant tumors. One of the main challenges to immunotherapy, which is related to recognition of tumor antigens by immunocompetent cells, has been solved through generation of antitumor vaccines based on dendritic cells. The complexity of this procedure is in that these vaccines are strictly individual and must be prepared strictly individually for each concrete patient. However, high sensitivity of the novel procedure which makes it applicable even for patients with grades III and IV of cancer encourages hope that it will afford effective treatment and reduce metastatic growth, especially when used in combination with other concomitant immunochemotherapeutic techniques.

The expression of cell adhesion molecules, P- and E-selectins, ICAM-1, and VCAM-1, was studied in cultured human vascular endothelial cells (ECs) infected by herpes simplex type I virus (HSV-1). It was shown that ECs without any signs of the cytopathogenic effect (CPE) expressed on their surface P- and E-selectins as soon as 24 h after infection. No appearance of VCAM-1 or increase in ICAM-1 expression was detected. Peripheral blood mononuclear cells (PBMCs) isolated by gradient centrifugation adhered preferentially with HSV-1-infected morphologically unchanged ECs but not with cells modified in result of CPE. The interferon and cytokine production by PBMCs was assayed after their contact with infected and glutaraldehyde-fixed ECs. The secretion of IFN-alpha, IFN-gamma, IL-1, IL-6, and TNF-alpha (but not of IL-4) was found to be inducible and correlated with the multiplicity of infection. Obtained results allow to consider a described cell culture system as a model for further investigation of initial stages of HSV-1 infection and of pathogenesis of vascular disease.

Interleukin-12 (IL-12) is an immunomodulatory cytokine with broad spectrum of activities, central of which are stimulation of NK cells, and promoting differentiation of T helper cells towards Th1 phenotype. IL-12 consists of two unrelated subunits, p35 and p40. Recently discovered cytokine, IL-23, which has both unique properties and those overlapping with IL-12, also contains p40 associated with another subunit, p19. Both IL-12 and IL-23 transmit the signal through receptors associated with JAK-STAT pathways. One of the critical components in the control of both IL-12 and IL-23 regulation is the transcriptional control of p40 gene which is induced in macrophages and dendritic cells in response to bacterial endotoxin, IFN-gamma and other stimuli. In the present study we report on the structure of the transcriptional unit of the murine p40 gene, its promoter and inducible expression of p40 in murine macrophages. Our findings are consistent with multi-level regulation of p40 expression.

Human alpha-fetoprotein (AFP) is capable of modulating cellular proliferative processes. A study has been made of the regulatory properties of a synthetic peptide corresponding to the part of the human AFP molecule participating in receptor interaction, the peptide consisting of seven amino acids and having an amino acid sequence LDSYQCT. The study was carried out on the lymphocytes of the peripheral blood of six patients with immune myocarditis in the period of exacerbation of the illness. For such patients a marked increased level of expression of early activation antigens with parallel disturbance of the induction of Fas-mediated apoptosis is typical. It is shown that the peptide had hardly any effect on the expression of early markers of activation of CD23, CD25 and CD71 lymphocytes in the patients being observed. Due to the effect of the peptide, the expression of the late activation antigen HLA DR, greater in patients with immune myocarditis in the period of exacerbation of the illness, is significantly reduced from 15.36 +/- 1.77% to 9.21 +/- 1.46% (p < 0.05). To the contrary, the expression of a receptor of Fas-mediated apoptosis, reduced in the period of exacerbation of the illness, significantly increases under the effect of the peptide AFP(13-19) from 2.85 +/- 0.57% to 9.09 +/- 1.37% (p < 0.01). Thus, the use of the synthetic AFP fragment makes it possible to restore the normal level of the activation apoptosis of lymphocytes in vitro in the case of diseases, at the base of which lie a process of immune damage.

The purpose of the present study was to find peculiarities of the immune response to the invasion of Demodex folliculorum and Demodex brevis mites. Sixty-six patients with human demodicosis were included in this study. The Demodex mites' density was more than 5 per 1 cm(2). The immune response was evaluated by the identification of membrane markers of the different immune cells by monoclonal antibodies. A significant decrease of the percentage of various parameters was found: the decrease for CD5(+) cells was in 1.4, for CD3(+) in 1.7, for CD4(+) in 1.5, for CD8(+) in 1.5, for CD25(+) in 1.3, for CD71(+) in 1.5, for CD20(+) in 1.2, for IgM in 1.2 and for IgG in 1.1 times. On the other hand, some parameters appeared to be elevated: for CD25(+) B cells in 1.5, for IgA in 1.9 and for circulating immune complexes in 1.4 times in patients with D. brevis infection in comparison with patients with D. folliculorum. The development of two variants of the effector response to the invasion of two different Demodex mites' species was shown: the classic expansion of the humoral reaction with the production of IgM and IgG in the case of D. folliculorum, and the activation of non-specific defense cells in the case of D. brevis. The particular capability of D. brevis to suppress T-cell compartment of immunity was distinctly observed in our comparative study. Thus, there are sharp immune distinctions during an invasion of the two species of human Demodex mites.

Twenty six patients with tetralogy of Fallot at the age from 1 to 3 years old were examined. All examined patients required surgical correction of heart defect and were operated under conditions of artificial circulation. All patients were in a status of relative compensation or subcompensation. The level of a saturation SaO(2) among patients with tetralogy of Fallot in peripheral arterial blood was equal to 66.27 +/- 7.2%. The purpose of work was to study the dynamics of immunological parameters in patients with tetralogy of Fallot in the postoperative period. The complex dynamic study of immune status was carried out to resolve such a task. Identification of membrane markers of peripheral blood immunocompetent cells was made by flow cytofluometry with the usage of monoclonal antibodies to antigens: CD3, CD4, CD5, CD8, CD11b, CD16, CD22, CD25, CD45 RA, HLA DR, CD95. The parameters were determined in dynamics: before operation, on the 7th, the 30th day and after 3 months after operation. Stabilization of parameters of the immune status among patients with tetralogy of Fallot, has been found in the postoperative period and was maintained within 3 months. Apparently it may be due to normalization of cardiohemodynamics, and as a consequence the stabilization of metabolic processes, undoubtedly, rendering modulating effects on immune system of children. However remaining failure of functional activity of immunocompetent cells is the reason to the usage of immunocorrection therapy with the purpose of faster stabilization of immune disbalance.

Our investigation is an attempt to confirm the probability to use the cycloferon for the extracorporeal immunopharmacotherapy. For this aim the leukocytes, obtained from 5 ml of venous blood of 17 healthy individuals, were stimulated by different doses of cycloferon during 1 h and after 24 h we determined interferon-alpha (IFN-alpha) concentration, tumor-necrosis factor-alpha (TNF-alpha), intreleukin-4 (IL-4) in the supernatant of stimulated and intact cells. Obtained results suggest that incubation of the blood leukocytes with cycloferon lead to the evident increase of IFN-alpha production. Dose-dependent effect of the stimulation is observed in the range of the cycloferon concentrations from 50 mg/l to 200 mg/l. Cycloferon poorly induces IFN-alpha production by leukocytes (50-150 ng/l) in comparison with phytohemagglutinin and other non-specific or bacterial stimulators. However, such quantity of IFN-alpha may be adequate to stimulate immune response, if the patient is reinfused by large amount of the autologous leukocytes, activated by cycloferon, isolated from 100-400 ml blood. The influence of cycloferon is less evident in the production of TNF-alpha, IFN-gamma and IL-4 by leukocytes at the range of the studied doses. It should be noted that the individual peculiarities of donor leukocyte reaction may be seen in response to the cycloferon. Obtained results suggest the principal possibility to use autologous leukocytes extracorporeally activated by IFN inductors for the immunotherapy.

This work deals with the problem concerning the mechanisms of triggering the demyelinating process by viruses as the consequence of molecular mimicry between viral antigens and the immunodominant region of the myelin basic protein with the subsequent involvement of reactions, mediated by T helper cells 1 and 2. Special emphasis is made on the new data indicating that reagin mechanisms play an active role in the development of neuropathology, corresponding to the results obtained by the authors in the study of humoral response in multiple sclerosis patients. Thus, the presence of pronounced total and specific IgE response was established to myelin basic protein, correlating with more severe clinical manifestations of the disease. Taking into account the viral nature of the demyelinization, the authors studied a number of humoral characteristics of immune response, indicating the degree of the involvement of T helper cells 1 and 2 into the pathogenesis of acute viral encephalitises. The determination of these characteristics was carried out with the use of original methods developed by the authors. The analysis of the results obtained in this study revealed the obvious presence of relationship between the involvement of autoimmune and atopic response in children with acute viral encephalitises and the manifestation of molecular mimicry of corresponding viruses with the immunodominant region of myelin basic protein. The most prognostically unfavorable group was the group of children having rubella, adenovirus and herpetic encephalitises.

The discovery of opioid ligand, beta-endorphin (betaEPh), in tactivin widens our knowledge about peptides synthesized by the thymus and allows to study new aspects of integration of the principal elements of immune and nervous systems within the integral immunoneuroendocrine network. Various produced lots of tactivin contain from 2 to 5 pM/l of betaEPh which provides a number of properties of this preparation. betaEPh is an important integral part of tactivin, as the action of tactivin "purified" of betaEPh truly differs from the effects of the total preparation: both in the norm (57 healthy children) and in pathology (30 patients with pyelonephritis), these preparations acted in vitro in different ways on lymphocytes with phenotypes CD3(+), CD4(+), CD8(+), CD38(+), CD22(+). Their influence on the functional activity of monocytes of the peripheral blood differed as well. All these effects of total tactivin and betaEPh-free tactivin were partially realized through &mgr;- and delta-opioid receptors. So, the removal of betaEPh did not "liberate" tactivin from displaying opioid activity, and consequently tactivin contains not only betaEPh, but also other ligands of &mgr;- and delta-types. Tactivin produces a direct and pronounced effect on monocytes of peripheral blood of healthy people and patients. The sensitivity of immunocompetent cells to betaEPh has been shown to be at the various levels and paradoxicality of action of this ligand may be related to the heterogeneity of receptors, through which betaEPh reveals its influence. A wide range of biological activity of tactivin and betaEPh with respect to standard parameters of healthy children is fair and its expediency is obvious as the immunocompetent cells of a healthy child can't help reacting to the peptides incoming from the thymus into blood in cases of antigenic or non-specific responses. One can evaluate the "contribution" of betaEPh to the size and importance of generalized effect of tactivin, as well as the role of intersystemic mediator betaEPh probably may include the initiation and coordination of immunotropic and bioregulating properties of thymic preparation.