Nobel prizes for investigations in immunology (1901‑2018)
1901. Nobel prize for implementation of immune sera for treatment of diphtheria and other infectious diseases
1905. Nobel prize for investigations in relation to tuberculosis
1913. Nobel prize for investigations of anaphylaxis
1919. Nobel prize for investigations in immunity (awarded in 1920 )
1930. Nobel prize for discovery of human blood groups
1951. Nobel prize for his discoveries concerning yellow fever and how to combat it
1957. Nobel prize for investigations of structure and function of antihistaminic drugs and other synthetic antagonists
1972. Nobel prize for investigations of the chemical structure of antibodies
1977. Nobel prize for the development of radio-immunoassays of peptide hormones
1984. Nobel prize for theories concerning the specificity in development and control of the immune system
1984. Nobel prize for the discovery of the principle for production of monoclonal antibodies with hybridomas
1987. Nobel prize for discovery of the genetic principle for generation of antibody diversity
1990. Nobel prize for discoveries concerning organ and cell transplantation
1996. Nobel prize for discoveries concerning the specificity of the cell mediated immune defence
1997. Nobel prize for the discovery of Prions - a new biological principle of infection
2008. Nobel prize for discovery of human immunodeficiency virus (HIV)
2011. Nobel prize for investigations of the activation of innate immunity
2011. Nobel prize for discovery of the dendritic cell and its role in adaptive immunity
2018. Nobel prize for discovery of cancer therapy by inhibition of negative immune regulation
2018. Nobel prize for the phage display of peptides and antibodies

Иммунология № 3, 2022

Immunologiya

The journal covers major theoretical and practical issues in general and applied immunology and allergology. It disseminates the results of original research in the fields of immunogenetics, molecular and cellular immunology, immunochemistry, immunomorphology, clinical immunology, and immunopathology.


Current issue
3 . 2022
Hot points of immunology

Interferon system for COVID-19

Abstract

SARS-CoV-2 is the causative agent of COVID-19 and infects the respiratory tract, blood cells, gastrointestinal tract, kidneys, liver, heart, brain and other organs. The ability of SARS-CoV-2 to escape from immune surveillance leads to deregulation of the immune response, cytokine storm and extensive tissue damage to infected organs. It is assumed that the pathogenesis of the deterioration of the course of COVID-19 is much more complicated and one of the mechanisms for the escape of SARS-Cov-2 from the influence of innate immunity is the inhibition of signaling pathways for the production and action of interferon (IFN). This review summarizes the role of the IFN system in SARS-CoV-2 infection and discusses the sophisticated mechanisms that coronaviruses have developed over the course of evolution to evade immune surveillance and suppress IFN responses. The IFN-related issues of counteraction to SARS-Cov-2 infection and the IFN-dependent adverse course of COVID-19 is also discussed.

Immunogenetics

Genome-wide DNA methylation profi le and expression of TLR2, TLR9, IL4, IL13 genes in pediatric patients with atopic dermatitis

Abstract

Introduction. Atopic dermatitis (AD) is a multifactorial disease, resulted from complex interactions between genetic and environmental factors. Epigenetic mechanisms involved in the gene expression regulationmay clarify how environmental exposure affects the risk of allergy development.

The aim of this study is to conduct a comprehensive analysis of the immune mechanisms (methylome; gene expression profile of TLR2, TLR9, IL4, IL13) locally and systematically in pediatric patients with moderate and severe AD.

Material and methods. With the use of DNA new generation sequencing technology (Oxford Nanopore Technologies Ltd) we performed a DNA methylation genome-wide study in atopic patients’ biopsies. At the same time the expression level for genes TLR2, TLR9, IL4, IL13 was assessed in the skin and mononuclear blood cells using real-time polymerase chain reaction.

Results. Targeted gene expression analysis revealed a significant (p ≤ 0.017) increase in the levels of TLR2, TLR9, IL4, IL13 expression in the blood of patients with AD compared with the group of comparison, as well as a decrease (p ≤ 0.05) in the levels of TLR2, TLR9, IL4 expression in affected skin compared to the group of comparison. We detected loci that were differentially methylated in atopic patients and healthy donors.

Conclusion. It is important to have a complete understanding of the AD pathogenic mechanisms. New insights on epigenetic and immunological markers associated with the risk of AD development will help to create new prognostic approaches in the management of patients with atopic pathology.

Cellular immunology

Effects of interaction between circulating CD4+CCR6+ T cells and B-lymphocytes

Abstract

Introduction. The chemokine receptor CCR6 is expressed on a portion of mature circulating CD4+CD45RO+-T-lymphocytes and gives them the potential to migrate into Peyer’s patches, inflamed gastrointestinal mucosa, and skin. The group of CD4+CD45RO+CCR6+ blood T-lymphocytes includes cells with various functions, in particular, pro-inflammatory T-helper-17 (Th17) and Th1, as well as anti-inflammatory FoxP3+ regulatory T cells. In addition, this group includes a small number of cells with the phenotype of follicular T-helper cells (fTh), professional stimulators of the humoral immune response.

The aim of the study was to evaluate the ability of blood CD4+CCR6+ T cells to help B-lymphocytes, as well as the response of T-helper subgroups to interaction with B cells.

Material and methods. Total pool of CD4+ T cells, CD4+CD45RO+CCR6+ T cells, or naive T-helper cells (nTh) were isolated from the blood of healthy adult donors, cultured with allogeneic B lymphocytes, and immunoglobulin production and T cell response were evaluated.

Results. It has been shown that mature CD4+CCR6+ T cells stimulate the production of IgM and IgG in mixed culture of T and B lymphocytes more strongly than nTh or total pool of CD4+ T cells. The interaction of CD4+CCR6+ T cells with B lymphocytes led to the expansion of Th17 and Th1/Th17 cells in culture without a noticeable increase in the number of Th1 and fTh cells. At the same time, nTh or undivided CD4+ T cells, activated by contact with allogeneic B lymphocytes, preferentially differentiate into fTh-like cells.

Conclusion. CD4+CCR6+ T cells effectively help B-lymphocytes, which is accompanied by the expansion of Th17 and Th1/Th17 cells, but not Th1 and fTh cells.

Phenotypic and functional characteristic analysis of THP-1 cell line as a model of infl ammation

Abstract

Introduction. THP-1 cell line represents one of the common research models for monocyte/macrophage-mediated inflammation.

Aim – to study the properties of THP-1 monocytes activated with bacterial lipopolysaccharides (LPS), influenza virus strain A/Puerto Rico/8/34 (H1N1), and X-ray irradiation.

Material and methods. The cell phenotypic and functional profiles were studied with light microscopy, RT-PCR with reverse transcription, and flow cytometry.

Results. We determined that HSP90, HPRT, and GAPDH were suitable reference genes for mRNA expression normalization upon LPS, viral, or irradiation exposure, respectively. The gene metabolic markers of THP-1 cell responses to LPS (GAPDH), virus (HSP90, GAPDH), and irradiation (B2M) were determined suggesting the new targets for monocyte profiling in pathological inflammation. Finally, the comparison of pro-inflammatory cytokines and antigen-presenting activities of THP-1 cells showed the differential cytokine expression upon various stimuli.

Conclusion. The profiles of metabolic and functional activities can be further used for THP-1 and monocyte comparative analysis and confirm the utility of THP-1 cell line as a model of inflammation.

Clinical immunology

Preventive effectiveness of nasal interferon-gamma among adult volunteers against acute respiratory viral infections, including COVID-19 (in Russian)

Abstract

Background. In vitro studies showed effective viral infection block in case of pretreatment with exogenous interferons. Interferon-gamma is a unique immune interferon, actively expressed in patients with acute respiratory viral infections (ARVI) and defending the body from severe infection course.

Aim – to evaluate the safety and preventive effectiveness of nasal interferon-gamma protecting against ARVI, including COVID-19.

Material and methods. The study enrolled 630 adult volunteers with a negative PCR test result for SARS-CoV-2, without respiratory symptoms and contraindications to interferon-gamma. Participants were randomized (1 : 1) into 2 groups: the study group – with the use of a prophylactic course of nasal interferon-gamma, and the group of comparison – without a course of prophylaxis. All participants were given a diary for daily monitor respiratory symptoms, adverse events, and record the use of pharmacotherapy.

Results. Safety analysis found no differences between groups. During 28 days period a higher incidence of ARVI, including COVID-19, was observed in the group of comparison (13 vs 3 cases in the study group). The odd ratio was 0.224 (95 % CI: 0.040–0.826), p = 0.020. The total number of ARVI cases, including COVID-19, in the group of comparison during 2 months of research was 26 vs 6 in the study group. The odd ratio was 0.233 (95 % CI: 0.077–0.594), p = 0,001. The longest period of persistence of respiratory symptoms was obtained in the group of comparison (7 vs 4 days in the study group, р = 0.034).

Conclusion. Nasal interferon-gamma as a preventive measure contributes to a decrease of infection incidence of ARVI, including COVID-19.

Preventive effectiveness of nasal interferon-gamma among adult volunteers against acute respiratory viral infections, including COVID-19

Abstract

Background. In vitro studies showed effective viral infection block in case of pretreatment with exogenous interferons. Interferon-gamma is a unique immune interferon, actively expressed in patients with acute respiratory viral infections (ARVI) and defending the body from severe infection course.

Aim – to evaluate the safety and preventive effectiveness of nasal interferon-gamma protecting against ARVI, including COVID-19.

Material and methods. The study enrolled 630 adult volunteers with a negative PCR test result for SARS-CoV-2, without respiratory symptoms and contraindications to interferon-gamma. Participants were randomized (1 : 1) into 2 groups: the study group – with the use of a prophylactic course of nasal interferon-gamma, and the group of comparison – without a course of prophylaxis. All participants were given a diary for daily monitor respiratory symptoms, adverse events, and record the use of pharmacotherapy.

Results. Safety analysis found no differences between groups. During 28 days period a higher incidence of ARVI, including COVID-19, was observed in the group of comparison (13 vs 3 cases in the study group). The odd ratio was 0.224 (95 % CI: 0.040–0.826), p = 0.020. The total number of ARVI cases, including COVID-19, in the group of comparison during 2 months of research was 26 vs 6 in the study group. The odd ratio was 0.233 (95 % CI: 0.077–0.594), p = 0,001. The longest period of persistence of respiratory symptoms was obtained in the group of comparison (7 vs 4 days in the study group, р = 0.034).

Conclusion. Nasal interferon-gamma as a preventive measure contributes to a decrease of infection incidence of ARVI, including COVID-19.

Immunopharmacology

Evaluation of immunotoxic properties of pyrimidine derivatives

Abstract

Introduction. Currently, the problem of developing safe anti-infective drugs with antibacterial action against a wide range of pathogens is acute. In this regard, one of the main tasks of the preclinical stage of the development of potential drugs is to assess their possible toxic effects on the body as a whole and various systems, including the immune system. Pyrimidine derivatives are of particular interest as new active substances. Being an integral part of nucleic acids, pyrimidine bases provide a wide pharmacological activity, as well as a high profile of drug safety of drugs synthesized on their basis. Pyrimidine compounds have been found to have psycho- and neurotropic, sedative, immunotropic, regenerative, antitumor, antiviral, antimicrobial and other types of action.

The aim of the study was to evaluate the immunotoxic properties of the pyrimidine derivatives.

Material and methods. The study was carried out on 30 male mice of the NEA line 7–8 weeks of age with a body weight of 20–22 g. The animals were divided into groups: «control» – mice receiving intraperitoneal equivalent volume of water for injection; experimental animals receiving intraperitoneal for three days pyrimidine compounds 3-[2-(Naphthyl)-2-oxoethyl]-6-bromoquinazoline-4(3H)-on (VMA–13–06) at a dose of 39 mg/kg and 3-(2-Ter.- butyl-2-oxoethyl)quinazolin-4(3H)-on (VMA–13–11) at a dose of 24 mg/kg. The dose of the pyrimidine derivative was 1/10 of the molecular weight of the compound. Immunotoxic properties were evaluated according to the «Guidelines for conducting preclinical studies of medicines» (Mironov A.N., 2012) according to the following indicators: mass and cellularity of immune-competent organs; delayed-type hypersensitivity reaction (DTH); direct hemagglutination reaction (DAT); phagocytic activity of neutrophils (number of active neutrophils, phagocytic index and phagocytic number).

Results. It was found that the pyrimidine derivative 3-[2-(Naphthyl)-2-oxoethyl]-6-bromoquinazoline-4(3H)-on had an immunosuppressive effect on the cellular and humoral links of immunity, which manifested itself in a decrease in the mass and cellularity of the spleen, the DTH index and antibody titer in DAT, as well as a decrease in the phagocytic function of neutrophils, whereas the compound 3-(2-Tert.-butyl-2-oxoethyl)quinazoline-4(3H)-on did not have an immunosuppressive effect on the studied parameters.

Conclusion. Thus, the conducted studies indicate the absence of a new pyrimidine derivative 3-(2-Tert.-butyl-2-oxoethyl)quinazoline-4(3H)-on has immunotoxic properties, which makes it possible to further study in detail the pharmacological activity of this compound.

Methods

Supercationic peptide dendrimers as vectors for nucleic acids delivery to mammalian cells

Abstract

Introduction. The usage of nucleic acids (NA) for modulation of gene expression or introduction new genes is a cardinal trend in modern biomedical science. However, such manipulations require the use of efficient delivery vehicles that could provide transmembrane transfer, nucleotide chain stability, and delivery vehicles themselves. Promising delivery vehicles for NA described in this work are supercationic dendrimeric peptides (СDPs), which have a branched structure due to the presence of ε-amide bonds and are relatively stable under biological conditions.

The aim of the study – design and synthesis of non-toxic CDPs which, as we expect, will be capable to penetrate efficiently into mammalian cells and stimulate transfection of eukaryotic cultures with model DNA plasmids. Other aim was to access the relationship between the structure and activity of the CDP and also an assessment of nucleolin and nucleophosmin chaperone molecule’s role in the transmembrane transfer of the CDPs.

Material and methods. All peptides for this study were synthesized using solid-phase synthesis method with Fmoc-protection of α-groups, purified by solid-phase HPLC and analyzed by mass spectrometry. Their cytotoxicity was assessed by the MTT assay using cell cultures HeLa and FEH. We studied the relationship between the structure of CDPs and their transfection activity, which was characterized in cell cultures Hela and A549 by the expression of reporter genes for luciferase and green fluorescent protein. Transport activity and analysis of intracellular localization of the CDPs were studied by confocal fluorescence microscopy using specific fluorescently labeled antibodies and fluorescently labeled CDP.

Results. The synthesized CDPs had 3 functional regions (modules): the N-terminal supercationic module, represented by arginine residues, the central module, represented by a hydrophobic core of lysine residues with short hydrophobic inserts and the C-terminal hydrophobic module including cysteine residue intended for attaching a reporter group. The study made it possible to access the relationship between the transfection activity of the peptide with its charge and the hydrophobicity of the C-terminal fragment. It has been shown that chaperone molecules, nucleolin and nucleophosmin, are involved in process of transmembrane transfer of CDP into the cell nucleus.

Conclusion. New dendrimeric peptides promising for effective delivery of NA molecules into mammalian cells have been obtained. The role of the chaperone proteins nucleolin and nucleophosmin in the transmembrane transport of the CDPs has been established. In the cells of most malignant tumors, the level of expression of these chaperone proteins is increased; therefore, these peptides can also be considered as potential antitumor agents.

Reviews

Polymorphic variants of innate immunity genes in longevity and age-associated diseases

Abstract

Aging is one of the most complex biological phenomena that affects all human physiological systems, including the immune system, causing the process of immunosenescence. One of the manifestations of immunosenescence is the so-called inflammaging, which is considered an important risk factor for morbidity and mortality in the elderly, since chronic inflammation underlies age-related diseases. Genetic variants of pro-/anti-inflammatory factors of the innate immune response can be associated with the level of the inflammation and influence the predisposition to age-associated diseases, survival and achievement of longevity, altering the host’s response to the environment and endogenous stress. The review presents data on the association of polymorphic variants of innate immunity genes – TLR, NLRP3, pro-/anti-inflammatory cytokines – with longevity and age-associated pathology.

Immunotherapeutic role of interferon-γ at tuberculosis

Abstract

Tuberculosis remains one of the most wide-spreading infections and its treatment presents serious difficulties due to the development of drug resistance of the Mycobacterium tuberculosis and the distribution of HIV-associated tuberculosis. The reaction of the human immune system to tuberculosis infection is complex and multi-stage, depending on the immune response tension different variants of the immune response can develop and interferon-γ (IFN-γ) is one of the key factors in its implementation. M. tuberculosis has the ability to inhibit the synthesis of IFN-γ that contributes to the progression of tuberculosis disease. The synthetic IFN-γ eliminates the deficiency of endogenous interferon and improves the clinical and economic efficiency of tuberculosis therapy by accelerating the termination of bacterial excretion and restoration the normal function of the respiratory system including in HIV-associated tuberculosis.

Chronicle

The health of immune system: way that not passed yet (continue)

Abstract
Jubilees

On the anniversary of Professor Yuri Petrovich Reznikov

Abstract

Vitaly Visilievich Zverev

Abstract

Ravshan Inoyatovich Ataullakhanov

Abstract
EDITOR-IN-CHIEF
EDITOR-IN-CHIEF
Musa R. Khaitov

Corresponding member of Russian Academy of Sciences, MD, Professor, Director of the NRC Institute of Immunology FMBA of Russia

Оргздрав-2022. Эффективное управление в здравоохранении
РОСМЕДОБР 2021
Вскрытие
Medicine today

XXIII Всероссийский научно-образовательный форум "Мать и Дитя − 2022" 28 - 30 сентября 2022 года в очном формате состоится XXIII Всероссийский научно-образовательный форум "Мать и Дитя − 2022" - самое значимое мероприятие для акушеров-гинекологов и смежных...

Уважаемые коллеги, приглашаем принять участие в конференции "Бронхоэктазы: муковисцидоз и не только..." в Воронеже, которая состоится с 23 по 24 июня Организаторы: · Общероссийская общественная организация "Российское общество медицинских генетиков"; · НМИЦ...

7-8 июня 2022 года "Фёдоровские чтения" объединили молодых талантливых офтальмологов Летний сезон Общество офтальмологов России открыло Всероссийской научно-практической конференцией с международным участием "Фёдоровские чтения"! Это одно из немногих российских...


JOURNALS of «GEOTAR-Media»