Immunologiya

The review examines the pathogenesis of tuberculosis in young children. Particular attention is paid to the development of tuberculosis in children of this age in the pre-antibacterial era, since the disease developed naturally – without the influence of vaccination and chemotherapy.

Thus, much attention is paid to the analysis of the tragedy that occurred at the beginning of 1930 in the German city of Lübeck, when 251 newborn children, as a result of a tragic mistake, were administered a virulent strain of Mycobacterium tuberculosis (MBT) three times per os instead of the BCG vaccine. As a result, they developed tuberculosis and 77 (30.7 %) children died. Posthumously, 72 of them underwent a pathological-anatomical study and bacteriological culture of the material, which confirmed the presence of virulent MBT, and the picture of the development of the tuberculosis process until the moment of death was described, since the children died at different times after the administration of MBT, the last one died on the 313^th day.

The data obtained from autopsy have not yet been evaluated and fully characterized. Major contributions to the assessment of these events were made by P. Donald et al., who examined the documents describing these events. It is important to note that after this, the surviving children did not develop tuberculosis for 12 years, while they were monitored. Of the surviving children, 90 % had positive reactions to the tuberculin skin test, which could have been a reaction to both the introduction of virulent mycobacteria and, probably, the vaccine strain of BCG. Due to the low specificity of tuberculin tests, it was not possible to determine this reliably.

Only now it has been possible to obtain skin tests based on the MBT-specific proteins ESAT6 and CFP10, which make it possible to differentiate these conditions with almost 100 % specificity. Data from Russian scientists obtained during the period before the advent of anti-tuberculosis drugs are also presented.

The review also provides modern views on the development of tuberculosis in children, starting from intrauterine development, the moment of birth, based on an analysis of the immune mechanisms of the development of tuberculosis, which is especially important to consider when creating new vaccines against tuberculosis in children in different age groups.

Introduction. The accumulation of senescent cells with age is considered to be one of the causes of dysfunction of various organs and tissues during physiological aging of the organism. The immune system participates in the elimination of senescent cells, but it is also subject to aging itself. Cell aging is usually assessed by the specific activity of the enzyme associated with senescence β-galactosidase (SA-β-Gal). However, the activity of SA-β-Gal in the lymphocyte population of donors of different ages is insufficiently studied. Therefore, studying the aging processes in the immune system and the potential use of SA-β-Gal as a marker for senescent lymphocytes is of interest.

The aim of the study – assessment of SA-β-Gal activity in peripheral blood T lymphocyte populations that differ in surface activation markers in donors of different ages.

Material and methods. The study included 20 apparently healthy donors aged 21–32 and 50–61 years. Mononuclear cells isolated from peripheral blood were phenotyped with antibodies against surface markers, incubated with a substrate to determine SA-β-Gal activity, and analyzed using flow cytometry.

Results. It was found that T lymphocyte subpopulations positive for activation markers CD25 and HLA-DR have higher SA-β-Gal activity. The regulatory T lymphocyte population with the phenotype CD3⁺CD4⁺CD25^highCD127^low/– (CD4⁺-Treg) demonstrated significantly lower SA-β-Gal activity compared to the overall pool of CD4⁺-T cells. Significant differences in SA-β-Gal activity among donors of the two age groups were not observed, except for subpopulations with the phenotypes CD3⁺CD8⁺HLA-DR⁺ and CD3⁺CD8⁺HLA-DR⁺CD127^– (CD4⁺-Treg), where SA-β-Gal activity decreases with age.

Conclusion. Activated CD4⁺ and CD8⁺ effector T cells exhibit increased expression of SA-β-Gal compared to non-activated populations and decreased expression in CD4⁺-Treg lymphocytes, indicating differences in metabolic activity in these cell populations. We did not find a significant increase in the percent of SA-β-Gal^high-lymphocytes or an increase in its activity with age, which limits the use of this method for assessing age-related changes in the immune system. However, the activity of SA-β-Gal can be used as an additional indicator of T lymphocyte activation along with surface activation markers in donors of the studied age groups.

Introduction. The formation of long-term immune memory against SARS-CoV-2 in the population is an important goal for creating reliable «community immunity».

The aim of the study – to study the features of the formation of hybrid immunity under conditions of previous infection and subsequent vaccination.

Material and methods. 60 patients who had COVID-19 and/or were vaccinated with a vaccine based on SARS-CoV-2 peptide antigens were examined. The comparison group consisted of 20 practically healthy donors. The dynamics of immunological parameters during the formation of post-infectious, post-vaccination and hybrid immunity to SARS-CoV-2 were assessed.

Results. In patients with COVID-19, compared with practically healthy individuals, a decrease in the functional parameters of monocyte cells was noted; activation of T lymphocytes, a decrease in the level of B2 lymphocytes with an increase in the proportion of B1 lymphocytes. In the post-vaccination period, non-COVID-19 patients showed a decrease in the level of HLA-DR⁺ and TLR9⁺ monocytes, an increase in the level of T-regulatory cells against the background of increased expression of activation markers of T and B lymphocytes with a change in the ratio due to the B1 phenotype. In conditions of hybrid immunity, the level of memory T lymphocytes was increased, the functional activity of B lymphocytes was enhanced with a slight increase in the content of B1 lymphocytes.

Conclusion. The advantages of hybrid immunity over other variants are shown, consisting in the smallest shifts in key immunological indicators of innate and adaptive immunity with reliable increase of the synthesis of specific antibodies to various antigenic determinants of the virus.

Introduction. The axiom of immunology is the opinion that numerous cytokines, chemokines and growth factors act within the single cytokine network, which suggests the relevance of their research not in an isolated form, but in the form of interacting elements – pleiades.

Aim – to evaluate changes in the interdependent of the TNF–IL-1–IL-4–IL-6–IL-8–IL-10–VEGF cytokine group serum levels in healthy women and patients with uterine leiomyoma.

Material and methods. Using the observational version «case–control» study, 109 women 23 to 61 years old with leiomyoma (LM) and 92 women of the same age without this pathology were examined. All women underwent general clinical, standard instrumental and laboratory examinations. Cytokines levels were determined by the ELISA using «Vector Best» test systems (Russia). To detect the relationship between the studied markers, the correlation analysis was performed using the Spearman correlation coefficient, followed by graphical visualization and analysis of the structure of correlation relationships with the correlation graph method by Cytoscape 3.10.2.

Results. It was found that the development of uterine leiomyoma was accompanied by a significant (in fold) up-regulation of TNF, IL-1, IL-4, IL-6, IL-8 serum levels, in combination with the VEGF serum level down-regulation. Three variants of correlation pleiades were obtained – a group of general (nonspecific) correlations and two groups of orthogonal correlograms – one of them is characteristic only for the comparison group, and the second group is specific only for patients with LM.

Conclusion. The benign tumor process of the myometrium significantly affects the nature of functional connections in the studied fragment of the general cytokine network, which is clearly illustrated by changes in graphic elements in the correlation graph with the allocation of two alternative orthogonal groups of correlation galaxy, which are detected in healthy women and in patients with uterine leiomyoma.

Introduction. Cytokines can be an effective tool for immunotherapy of tumors, however, by the usual routes of administration – intravenous infusion and intramuscular or subcutaneous injections (systemic administration) – a small part of the injected cytokines can reach target cells in the organs of the respiratory system.

Aim – to demonstrate the possibility of prevention of breast cancer metastases using cytokine drugs and to present an algorithm for patient management.

Material and methods. An inhalation method of administration of pharmacopoeial cytokines (Refnot, Ingaron, Reaferon, Roncoleukin) was used to prevent the development of lung metastases in a patient with breast cancer who is under dynamic observation for suspected lung metastases.

Results. After 3 courses of cytokinotherapy, previously noted micro-nodes were not detected by PET-CT methods. Data for recent focal and infiltrative changes in the lungs were also not recorded. There was no increase in temperature or other adverse events.

Conclusion. Inhaled cytokine drugs can provide the approach of targeted and better tolerated comprehensive preventive antitumor immunotherapy in patients with possible respiratory metastases.

Introduction. Autosomal dominant STAT1-GOF (gain-of-function) pathogenic variants lead to combined immunodeficiency with CMC and autoimmune disorders. Heterozygous STAT1-GOF-mutation caused an enhanced activation with delayed STAT1 dephosphorylation. STAT1 depending cytokines affect negative regulation of gene transcription in naïve T cells, resulting in maturation of CD4⁺ lymphocytes into Th1 phenotype rather than Th17 phenotype. Besides that there are autosomal-dominant and autosomal-recessive variants which lead to loss of a STAT1 protein function (loss-of-function, LOF). Next-generation sequencing (NGS) has facilitated detection of novel variants. However, the biological relevance of novel mutations is often not clear and must be confirmed by immunological analysis.

The aim of this study was to develop and validate a method for assessing STAT1 protein phosphorylation.

Material and methods. The study included 17 patients with STAT1 pathogenic variants (STAT1-GOF n = 16 and STAT1-LOF n = 1), 7 patients with the variants of uncertain significance in the gene STAT1 and a cohort of healthy donors (n = 50). After the mononuclear fraction isolation, the cells were stimulated and STAT1 phosphorylation was evaluated by flow cytometry.

Results. We obtained reference values by comparing a cohort of STAT1-GOF patients with a healthy donors. The references were used to assess the variants of uncertain significance in the gene STAT1.

Conclusion. The method turned out to be sensitive and specific for detecting STAT1-GOF and STAT1-LOF genetic variants.

The authenticity (identity) of cell lines (cells) is one of the most important quality indicators of medicinal products containing viable human cells. Immunophenotypic characterization of human cells is fundamental to the identification of a cell therapy product before its clinical application. The most widely used method for phenotyping cell lines is flow cytometry. The study is devoted to the analysis of the specific aspects of cell line phenotyping methods validation. This study reviewed key parameters of the method validation process, as well as current data on validation specific aspects related to cell therapy products, reagents and equipment used, rare events and compensation.

The review presents the information on the use of monoclonal antibodies (MAbs) in the treatment of cancer. The mechanisms of MAbs action, their types, methods of production and the main approaches to their use in cancer therapy are considered. Modern MAb drugs are approved for use and are used for the treatment of hematological and solid malignancies. They are targeted drags due to their effects on specific molecules involved in the mechanisms of carcinogenesis and tumor growth.

The presented data show that the synthesis and production of monoclonal antibodies, as well as their conjugation with drugs or radionuclides, have advanced significantly over the past decades. The methods of tumor immunotherapy discussed in the article have either already shown their effectiveness in the treatment of malignancies or are at various phases of clinical trials. The development of modern, more advanced technologies will help solve existing problems and make the treatment of cancer patients more effective and safer.

More than 30 % of the world’s inhabitants suffer from allergies. Allergen-specific immunotherapy (AIT) is considered to be the only pathogenetic method of allergy treatment that can provide a long-term effect. This method involves regular administration of therapeutic allergens or allergy vaccines to reduce the severity of clinical manifestations of allergy by inducing immune tolerance to the target allergen. However, AIT has disadvantages: low quality of preparations of therapeutic antigens and allergy vaccines based on them, the risk of side effects, and the duration of the course of treatment. For more than a century of AIT use, significant progress has been made in the development of new immunotherapy technologies and in the study of allergy mechanisms. The molecular approach to the development of allergy vaccines is becoming increasingly popular. It makes it possible to improve their safety, efficacy and standardize the production process. In this review, the main stages of AIT development and various technologies for the development of therapeutic allergen preparations and allergy vaccines are discussed. Special attention is paid to modern molecular methods of immunotherapy. Current understanding of the pathogenesis of allergy and mechanisms of AIT are also summarized.

Mesenchymal stem cells (MSCs) have complex mechanisms of interaction with the immune system and are able to modulate innate and adaptive immune responses, as well as enhance angiogenesis. MSCs produce a variety of cytokines and chemokines that affect immune cell activity, inflammation and immune tolerance. Exosomes derived from MSCs also affect immune regulation. However, additional research and clinical trials are needed to fully exploit the therapeutic potential of MSC.