Vol 8, No 3 (2018)

REVIEW ARTICLES

THE ROLE OF INNATE IMMUNITY RECEPTORS (TLRs) IN MAINTAINING THE HOMEOSTASIS OF THE FEMALE GENITAL TRACT IN DEVELOPING PREGNANCY AND INTRAUTERINE INFECTION

Karaulov A.V., Afanasiev S.S., Aleshkin V.A., Bondarenko N.L., Voropaeva E.A., Afanasiev M.S., Nesvizhsky Y.V., Borisova O.Y., Aleshkin A.V., Urban Y.N., Borisova A.B., Voropaev A.D.

Abstract

The aim of the present systematic literature review is to summarize data on the role of TLRs in maintaining homeostasis of the female genitals, in maintaining the physiological development of pregnancy, provision of anti-infective resistance in pregnant women with intrauterine infection. The review substantiates the importance of TLRs of female genitals as a necessary and determining factor in the reaction to various changes in the environment, and also responsible for changes in metabolic, structural, or energy, in the maintenance of anti-infective resistance and homeostasis. As universal regulators of vital activity of organism TLRs in conjunction with other receptors of innate immunity provide maintaining the general reactivity and anti-infective resistance at the physiological level. In physiologically developing pregnancy in a background of immunosuppression in response to pregnancy TLRs during contact with infectious and non-infectious pathogens stimulate the production of nonspecific adaptive immunity factors (defensins, cathelicidins, histatines, etc.), which together with the non-specific innate factors lysozyme, complement, properdin, etc. support antiinfective resistance of the female genitals at a high level at the beginning of the infectious process. Possible violations of the development of pregnancy may be accompanied by changes in the response of TLRs to infectious and non-infectious factors until hyper-reaction, excessive inflammation or apoptosis, which requires adequate management of pregnancy. Was established the significance of the influence of pathogens of infectious and noninfectious origin in intrauterine infection indirectly through TLRs in the homeostasis of the organism, on the formation of breaches in anti-infective resistance at the organism and community level the identification of new pathophysiological and immunological pathogenetic mechanisms of development of pathological processes. IUI is a penetration of microorganisms into the tissues of fetus and it’s infection. The inhibition of the functional activity of TLRs is accompanied by the direct effect of the pathogen on the tissues, and during hyper-reaction of TLRs to pathogens revealed a pronounced inflammatory response in the fetus. The level of expression of TLRs correlates directly with the severity of the process that can be considered as early markers of infection. Depending on the nature of the pathogen an increased expression of one or the other TLRs is observed. Explained the lack of symptoms, the possibility of atypical manifestations, the asymptomatic course of infection.

Russian Journal of Infection and Immunity. 2018;8(3):251-262
pages 251-262 views

MECHANISMS OF INTERRACTION OF HELICOBACTER PYLORI WITH EPITHELIUM OF GASTRIC MUCOSA. I. PATHOGENIC FACTORS PROMOTING SUCCESSFUL COLONIZATION

Pozdeev О.К., Pozdeeva А.О., Valeeva Y.V., Gulyaev P.E.

Abstract

H. pylori is a Gram-negative, crimp and motile bacterium that colonizes the hostile microniche of the human stomach roughly one half of the human population. Then persists for the host’s entire life, but only causes overt gastric disease in a subset of infected hosts. To the reasons contributing to the development of diseases, usually include: concomitant infections of the gastrointestinal tract, improper sterilization of medical instruments, usually endoscopes, nonobservance of personal hygiene rules, prolonged contact with infected or carriers, including family members and a number of other factors. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic and duodenal ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, we are able to conclude that smart strategies are contributing to adaptation of the bacterium in an aggressive environment of a stomach and lifelong permanent circulation in its host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable conditions? Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of different gastric diseases in persons infected with this bacterium. A well-defined and long-term equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases the diseases which are listed above. In this review, we discuss the pathogenesis of this bacterium and the mechanisms it uses to promote persistent colonization of the gastric mucosa, with a focus on recent insights into the role of some virulence factors like urease, LPS, outer membrane proteins, cytotoxins, factors, promoting invasion. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium persist in relation to the many unfavorable features of living in the gastric microniche.

Russian Journal of Infection and Immunity. 2018;8(3):273-283
pages 273-283 views

M CELLS ARE THE IMPORTANT POST IN THE INITIATION OF IMMUNE RESPONSE IN INTESTINE

Bykov A.S., Karaulov A.V., Tsomartova D.A., Kartashkina N.L., Goriachkina V.L., Kuznetsov S.L., Stonogina D.A., Chereshneva Y.V.

Abstract

Microfold cells (M cells) are specialized intestinal epithelial cells that initiate mucosal immune responses. These unique phagocytic epithelial cells are specialized for the transfer of a broad range of particulate antigens and microorganisms across the follicle-associated epithelium (FAE) into the gut-associated lymphoid tissue (GALT) by a process termed transcytosis. The molecular basis of antigen uptake by M cells has been gradually identified in the last decade. Active sampling of intestinal antigen initiates regulated immune responses that ensure intestinal homeostasis. The delivery of luminal substances across the intestinal epithelium to the immune system is a critical event in immune surveillance resulting in tolerance to dietary antigens and immunity to pathogens (e.g., bacteria, viruses, and parasites) and their toxins. Several specialized mechanisms transport luminal antigen across the gut epithelium. Discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted delivery oral vaccine to M cells. Recent studies demonstrated that M cells utilize several receptors to recognize and transport specific luminal antigens. Vaccination through the mucosal immune system can induce effective systemic immune responses simultaneously with mucosal immunity. How this process is regulated is largely unknown. This review aims to show a new understanding of the factors that influence the development and function of M cells; to show the molecules expressed on M cells which appear to be used as immunosurveillance receptors to sample pathogenic microorganisms in the gut; to note how certain pathogens appear to exploit M cells to inject the host; and, finally, how this knowledge is used to specifically "target" antigens to M cells to attempt to improve the efficacy of mucosal vaccines. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells.

Russian Journal of Infection and Immunity. 2018;8(3):263-272
pages 263-272 views

ANTIMICROBIAL PEPTIDES — A POTENTIAL REPLACEMENT FOR TRADITIONAL ANTIBIOTICS

Musin K.G.

Abstract

Antimicrobial peptides are a heterogeneous group of molecules involved in the innate and acquired immune response of various organisms, ranging from prokaryotes to mammals, including humans. They consist of 12–50 amino acid residues; have different physico-chemical and biological properties. The most common feature is their ability to destroy the prokaryotic cell membrane, which causes cell death. In the action, the molecules of antimicrobial peptides are embedded in the target bacteriological cells and change their conformation, forming structures in some cases resembling channels. Some other molecules of antimicrobial peptides can cover the surface of a bacteriological cell and form a carpet, when they reach a critical mass they act like detergents. In addition, being positively charged molecules of such peptides, penetrating through the membranes of parasitic and bacteriological cells, bind to polyanionic RNA and DNA molecules. Among the benefits of antimicrobial peptides is their high metabolic activity, low probability of occurrence of addictions and side effects. In addition, bacteriological pathogens that previously did not have resistance to any antimicrobial peptide are difficult to develop a strategy to control them. In this connection, these peptides are the most promising moleculessubstitutes for traditional antibiotics. The article discusses the approaches and strategies of therapeutic use, the studies of antimicrobial peptides identified in recent years; The most frequently encountered mechanisms of interaction of antimicrobial peptides and a bacteriological membrane are described, the physicochemical properties of peptide molecules are described; the results of studies on the detection of resistance of some strains of bacteria to antimicrobial peptides and antibiotics in general are summarized.
Russian Journal of Infection and Immunity. 2018;8(3):295-308
pages 295-308 views

PERTUSSIS INCIDENCE AND THE EFFECT OF REVACCINATION OF PRESCHOOL AND SCHOOL CHILDREN

Kostinov А.M., Kostinov M.P.

Abstract

The review is devoted to the analysis of pertussis incidence of children in the age group of 5–7, as well as strategies of DTP immunization with the help of the drugs in foreign countries. Mass vaccination against pertussis began in the middle of the 20th century, which contributed to a reduction in incidence and mortality rate from this infection. However, in the last decade, there has been an opposite tendency of increasing incidence of patients among children under school age, school age and adults. Atypical forms of the disease and complications due to ARVI, respiratory mycoplasmosis and cytomegalovirus infections are described in the review. Various strategies for the use of whole-cell and acellular pertussis vaccines as part of DTP drugs are described, as well as the epidemiological effect of introducing an additional booster dose of vaccine to children under school age. The expediency of revaccination of children aged 6–7 in Russia is argued, which can help to reduce the overall incidence of pertussis. The research materials related to the study of the properties of acellular anti-pertussis vaccine, such as immunogenicity and safety in comparison with whole-cell vaccine, are analyzed. The main drugs and their composition, which are used to vaccinate children against pertussis, are described in the review. It is assumed, that the increase in the incidence among children and teenagers, with the appearance of atypical forms of pertussis, is associated with a number of factors, such as the spread of new genotypes of Bordetella pertussis bacterium, emerged from mutations, as well as short duration of immunity after vaccination with acellular drugs, in comparison with whole-cell, and the use of more modern methods of detecting the pathogen. The mechanisms of the immune response due to different types of pertussis vaccines are also reviewed. It is concluded, that revaccination of children aged 6–7 with an additional fifth dose of an acellular vaccine against pertussis, as part of the DTaP instead of the Td drug, which is regulated in the National Calendar of preventive vaccinations, will have a favorable effect on the epidemic situation with pertussis infection in Russia.

Russian Journal of Infection and Immunity. 2018;8(3):284-294
pages 284-294 views

MicroRNA AND TUBERCULOSIS

Eremeev V.V., Evstifeev V.V., Shepelkova G.S., Ergeshova A.E., Bagirov M.A.

Abstract

In 2015, more than 10% of tuberculosis (TB)-related deaths were attributable to M. tuberculosis with multiple drug-resistance (MDR-TB) and extensively drug-resistance (XDR-TB) (WHO 2016). In combination with insufficient commitment to the treatment regimen, the genetic heterogeneity and clonality of the patient's M. tuberculosis, as well as the poor permeability of the tuberculosis granuloma for the drug, can lead to monotherapy, despite the use of several drugs, which further promotes the spread of MDR and XDR-TB. Of particular concern is the rapid spread of resistance to newly introduced into clinical practice second-line drugs, intended for the treatment of MDR-TB — delamanid and bedaquiline. Thus, the spread of drug resistance to chemotherapy, along with the limited possibilities of chemotherapy in patients with MDR-TB and XDR-TB, dictate the need to supplement canonical chemotherapy with TB treatment methods directed at the host. MicroRNAs (miRs) are short sequences of single-stranded RNA that control up to 60% of genes encoding protein synthesis at a post-transcriptional level. Accumulating data points to the essential role of miRs in fine tuning the host response to infection, primarily by modulating the expression of proteins involved in the reactions of innate and adaptive immune responses. Despite the fact that the established functions of miRs activity are intracellular, a number of studies have discovered highly stable extracellular miRs circulating in blood. Currently, the possibility of using these molecules as biomarkers is being actively investigated. Chronic TB inflammation is characterized by parallel or step-bystep development of regulatory and pro-inflammatory processes that affect the severity and outcome of the disease. Both pro- and anti-inflammatory effects are elements of the bacterial strategy in the struggle for survival in the host organism. In this review we discuss the role of miRs as markers of tuberculosis infection, the nature and prognosis of the course of the disease, the involvement of miRs in the regulation of the innate and adaptive immunity in tuberculosis infection, and the perspectives for clinical usage of miRs as means for diagnosis and treatment of tuberculosis.
Russian Journal of Infection and Immunity. 2018;8(3):309-315
pages 309-315 views

ORIGINAL ARTICLES

IDENTIFICATION MARKERS OF INFECTION DUE TO C. TRACHOMATIS AND C. PNEUMONIAE, IN PATIENTS WITH DISEASES OF THE GASTROINTESTINAL TRACT

Bondareva N.E., Morgunova E.Y., Zigangirova N.A., Shapkin Y.G., Chalyk Y.V., Chalyk R.Y.

Abstract

 To date, clinical data have convincingly shown that C. trachomatis and C. pneumoniae infectious can cause serious diseases with severe complications and consequences. There are assumptions that the developed chronic chlamydial infection can become an important factor in the pathogenesis of the gastrointestinal tract diseases, which are manifested in the so-called post-infectious period. It is commonly known that chlamydial infection has a tropism to the cylindrical epithelium, which covers the human mucous membrane of the urethra, cervix, rectum, conjunctiva of the eyes and the throat. However, the role of the causative agents of chlamydial infections, such as C. trachomatis and C. pneumoniae, in the occurrence of the gastrointestinal tract diseases has not been studied. In order to study the possible relationship between the gastrointestinal diseases and the presence of chlamydial infection markers, we have selected a group of patients with the gastrointestinal diseases and detected antibodies to C. trachomatis and C. pneumoniae and DNA of these pathogens in blood serum, liver biopsy and bile ducts. As a result, C. trachomatis DNA in blood serum was detected in 50% of cases, and in liver biopsies — in 59.3%. A new approach has been developed in the serological diagnosis of chlamydial infection caused by C. trachomatis, which allowed for revealing diagnostic antibody titers in 51.9% of cases in this group of patients, and in the comparison group — in 11.6% of cases. Among 50% of patients, in whom DNA was revealed in blood serum, it was also revealed in 64.3% of cases in biopsy samples of gastrointestinal organs. Upon detection of C. trachomatis DNA in blood serum, antibodies to the “cultural” antigen were detected in 60.1% of cases, and with the simultaneous detection of C. trachomatis DNA in blood serum and gastrointestinal organs, they were found in 72.2% of cases. Simultaneous detection of C. trachomatis, both in blood serum and in the gastrointestinal tract, may indicate the ability of C. trachomatis to spread hematogenously and infect organs away from the primary focus of infection. The obtained data absolutely require further study in light of the identification of the relationship between the detection of the pathogen and the development of the gastrointestinal pathology. But in general, the results are not yet studied evidence of the possible gastrointestinal organs infection by C. trachomatis.

Russian Journal of Infection and Immunity. 2018;8(3):316-324
pages 316-324 views

THE SPANISH INFLUENZA VIRUS: TREATS TO THE PORTRAIT AFTER 100 YEARS

Kharchenko E.P.

Abstract

The purpose of the study was to compare molecular characteristics of genes and proteins of pandemic influenza strains and find features of the 1918 Spanish influenza virus. Computer analysis has shown that the genes of the Spanish influenza virus in contrast to other pandemic strains contain optimal quantity of long complementary sequences that allow to obtain a supramolecular assembly of 8 virus RNA in according to a model ensuring selective packing of one copy of each virus RNA by the only possible scheme and high transmission to induce infection by single virions. Other pandemic strains contain redundant or insufficient quantity of complementary sequences that allow an assembly of its genome by means of some models including a stochastic one and occurrence of virions with incomplete genome, that is influenza virusts can exist primarily as a swarm of complementation-dependent semi-infectious virions. Analysis of an HA gene of the Spanish influenza virus found out exclusion from its translation code four triplets (CGG, CGA, CGC и CGU) coding arginine. This exclusion is observed in all the HlNl strains isolated during 100 years. Coding arginine in an HA gene of HlNl strains is provided by only triplets AGG and AGA. A NP gene of the Spanish influenza virus in contrast to other pandemics strains is avian-like and its NP protein is characterized by elevated quantity of arginine and decreased quantity of lysine that is considered as viral adaptation to avian body temperature. Prevalence of arginine provides more high positive charge for the Spanish influenza NP protein and its more powerful interaction with RNA and consequently more high thermal stability of the its RNP in comparison with the RNP of other pandemic strains. Potential consequence of existence of the avian-like NP in the Spanish influenza virus could be its high pathogenicity as infection fever creates optimal temperature for virus replication. These new data obtained by computer analysis of genomes in the Spanish influenza virus and other pandemic strains (altogether information about its proteins) can potentially be used to track pre-pandemic strains among circulating influenza A viruses and detect the formation of a possible trajectory of pandemic alert.

Russian Journal of Infection and Immunity. 2018;8(3):325-334
pages 325-334 views

IMMUNE INTERLAYER TO TICK-BORNE ENCEPHALITIS VIRUS IN HUMAN POPULATION OF TRANSBAIKALIA AS AN INDICATOR OF NATURAL FOCI ACTIVITY

Turanov A.O., Nikitin A.Y., Andaev E.I.

Abstract

Studying of immune interlayer value to tick-borne encephalitis virus in human population of the Transbaikalia Territory resulted from natural immunization of the healthy population in 31 Municipal areas in 2011–2016 is presented. Human selections were formed proportionally to the population size in the concrete human settlement among persons of the various age and professional groups living at this territory not less than 10 years and unvaccinated against tick-borne encephalitis virus. Total 4367 blood sera were investigated. Laboratory testing for antibodies of G class to tick-borne encephalitis virus in blood sera of the human population was performed by immune-enzyme analysis using a set of reagents “VektoVKE-IgG” of Joint-Stock Company “Vektor-Best” (Novosibirsk city). The monitoring data indicated the presence of natural immunity to tick-borne encephalitis virus in the human population. Mean annual level of immune interlayer in Municipal areas varied from 3.1 to 52.7% (in Transbaikalian Territory — 13.1±0.51%). High level (from 20 to 52.7%) was characteristic for mountain-taiga-forest-steppe zone (Krasnochikoisky — 23.8±3.36%; Uletovsky — 52.4±4.48%; Gazimuro-Zavodsky — 29.4±4.94% districts) and mountain-tundra-taiga zone (Tungokochensky district — 20.0±3.58%). In steppe zone the level of immune interlayer was lower and observed in districts with elements of south-taiga larch and pine forests. It was established that levels of the immune interlayer in human population living in mountain-taiga-foreststeppe and mountain-tundra-taiga zones authentically higher than in steppe area — t = 3.8; Р < 0.001 and t = 2.27; Р < 0.05, respectively. Distinctions in the value of the immune interlayer between mountain-tundra-taiga and mountain-taigaforest-steppe zones were non-authentic: t = 0.1; P > 0.05. Active circulation of tick-borne encephalitis virus was accompanied by authentic (Р < 0.01) increase of the interlayer in persons with the virus antibodies in 2014–2016 (15.8±0.69%) in comparison with 2011–2013 (9.7±0.78%). Also it was noted in all landscape zones: in steppe zone the increase was to 42.8% (P > 0.05); in mountain-taiga-forest-steppe — to 61.3% (P > 0.05); in mountain-tundra-taiga — to 150.0% (Р < 0.01). It was not possible to reveal correlation between the recourse for medical aid and the value of immune interlayer in the population formed as a result of latent immunization. Results of the population immunity studying essentially expand our knowledge about the condition of the natural foci and dynamics of development of the epidemic processes in it, and can be used at planning of the preventive actions.

Russian Journal of Infection and Immunity. 2018;8(3):335-340
pages 335-340 views

INFLUENCE OF POPULATION IMMUNITY PECULIARITIES ON THE STRUCTURE OF MEASLES AND RUBELLA PREVALENCE

Toptygina A.P., Smerdova M.A., Naumova M.A., Vladimirova N.P., Mamaeva T.A.

Abstract

According to the lasting serological investigations of patients with rubella and measles, a major factor that determines the resistance to the infections is specific antibodies, that are still circulating in blood of recovered persons during their life. Since vaccinated people are also included in this concept, serological monitoring of people different ages who get vaccinated against rubella and measles is conducted in Russia. However the discrepancy between specific immunity intensity and the measles incidence was showed last years. Using “Vector Best” kits, the study of the anti-measles and antirubella population immunity in scale of age: under 1 year, 1–2 years, 3–6 years, 7–14 years, 15–17 years, 18–30 years, 31–40 years, 41–50 years, and 51–60 years was carried out in Moscow and Moscow region in 2013 (period of unfavorable epidemic situation). The serum probes were obtained from 654 random healthy donors and 646 patients with serologically confirmed measles infection. As a result, gradual increase of percentage of people with protective antibodies to rubella and measles have been demonstrated: 81.3% donors aged 7–14 years were protected from measles and more than 90% — from rubella. Moreover, percentage of individuals who have had immunity to rubella were the same in adults too. The most marked increase of percentage of seronegative persons to measles virus (40% and more) was in age from 18 to 30 years, and in groups over the age 40 years old protection reaches 85–95%. Comparison between percentage of measles patients different ages and percentage of persons with protective antibodies in serum have demonstrated significant negative correlation between measles prevalence and the level of specific antibody in population (r = –0.76). According to the results, increase (to 28%) and decrease (to 2.9%) of measles patients aged 18 to 30 and 51 to 60 years are based on decrease (to 55%) and increase (to 95%) of persons with protective immunity, respectively. Results of analysis of measles prevalence in different ages have demonstrated, that among adult measles patients (18–50 years) 14.5% responded on infection by secondary immune response; among children and teenagers there were no such patients, that proves the significant effectiveness of prophylactic vaccines.

Russian Journal of Infection and Immunity. 2018;8(3):341-348
pages 341-348 views

ANTIMICROBIAL SUSCEPTIBILITY OF ENTEROBACTERIACAEISOLATED FROM INTESTINAL MICROBIOTA OF RESIDENTS OF THE REPUBLIC OF GUINEA AND RUSSIA (SAINT PETERSBURG)

Egorova S.A., Makarova M.A., Kaftyreva L.A., Suzhaeva L.V., Zabrovskaia A.V., Matveeva Z.N., Voitenkova E.V.

Abstract

It is known that resistant Enterobacteriacaestrains can be a part of human microbiota. While colonizing the body of a healthy person, resistant strains do not cause diseases, while the healthy person becomes carrier and source of such strains or the resistance genes to the external environment. The aim of the study was to compare the antimicrobial susceptibility of opportunistic Enterobacteriacaeisolated from feces of residents of the Republic of Guinea (121 strains) and Russia, Saint Petersburg (897 strains). The antimicrobial susceptibility was determined by the disc-diffusion method according to the national russian Clinical Guideline “Antimicrobial susceptibility testing of microorganisms” using discs and Muller-Hinton agar manufactured by Oxoid. Resistance mechanisms were tested in bacterial strains non-susceptible to beta- lactams using confirmatory phenotypic and molecular tests. Resistant strains were detected significantly more often in the intestinal microbiota of residents of the Republic of Guinea, than of Saint Petersburg (83.5 and 28.7 per 100 strains studied, respectively), including strains with multidrug resistance (47.9 and 11.1, respectively). The residents of the Republic of Guinea have a high frequency of isolation of Enterobacteriacaeresistant to “old” antibiotics, which were often used in the 1970s, but rarely used in Russia and other European countries: tetracyclines (63.2), trimethoprim/ sulfamethoxazole (59.5) and aminopenicillins (48.4). The frequency of detection of strains resistant to modern clinically significant antibiotics (extended spectrum cephalosporins, f luoroquinolones, aminoglycosides) was the same in residents of the Republic of Guinea and Saint Petersburg. Resistance to beta-lactams in Enterobacteriacaestrains isolated both from the residents of the Republic of Guinea and from Saint Petersburg is due to the same mechanism — the production of beta-lactamases — broadspectrum and extended spectrum- of various genetic families. This data corresponds to world global trends in the antimicrobial resistance in Enterobacteriacae: resistance to aminopenicillins in E. coliis due to the production of broad-spectrum beta-lactamases TEM-1 (80% of strains from residents of the Republic of Guinea and 86.5% from Saint Petersburg), and resistance to extended spectrum cephalosporins — the production of extended spectrum beta-lactamases of the CTX-M1 genetic group (72.7 and 67.6% respectively). Our research has shown that the intestinal microbiota of the inhabitants of different continents (Europe and Africa) contains the strains (Klebsiella pneumoniae and Escherichia coli) resistant to clinically significant antibiotics (beta-lactams) due to single mechanism globally spread in Enterobacteriacae.

Russian Journal of Infection and Immunity. 2018;8(3):349-354
pages 349-354 views

MODIFYING EFFECT OF INHALATION CHEMICAL LOAD ON THE CONTENT OF CYTOKINES AND IMMUNOGLOBULINS IN ADOLESCENTS WITH LAMBLIA INFECTION

Masnavieva L.V., Kudaeva I.V.

Abstract

Giardiasis ranks second in the structure of parasitic diseases in Russia of the last decade. Infestation Giardia is associated with clinical signs of allergic reactions, imbalance parameters of the T- and В-lymphocytes, changes in the concentration of cytokines and immunoglobulins. Air pollution by chemical compounds also affects the immune system, stimulates production of pro- and anti-inflammatory cytokines, immunoglobulins. It can be assumed that the response of the organism to lamblia invasion will undergo changes under conditions of chemical inhalation exposure. The purpose of this study was to evaluate the content of cytokines and immunoglobulins in adolescents with giardiasis with an inhalation chemical load. 295 adolescents aged 13–16 with I–III health groups who did not have any at the time of the examination, exacerbation of any diseases and complaints of the work of gastrointestinal organs were included in the survey. Cellular blood composition with differential count of the leukocyte formula were studied in schoolchildren. The content of antibodies to lamblia, interleukins-2 and -10, interferons-alpha and-gamma, immunoglobulins A were studied in the blood serum by the method of enzyme immunoassay. Evaluation of individual inhalation chemical load by substances tropic to the immune system was carried out for each person. Data on the content of impurities in ambient air, indoor air, information on the organization of educational process and rest of students and their anthropometric parameters were taken into account when calculating chemical loads. Groups were formed after evaluation of antibodies to lamblia. Persons with Giardia invasion made up group I, school children without giardiasis were included in group II. Subgroups with a hazard index of immunity less than 2, 2 or more selected in each group. It has been established that changes in the relative content of basophils and monocytes, an increase in the levels of interferons-alpha and gamma, interleukin-2 and immunoglobulin A in adolescents with giardiasis occur at indexes of the development of pathology of the immune system less than 2. Adolescents with hazard indices of immunity equal to 2 or more decreased the content of immunoglobulin A and interferon-gamma and no differences in concentrations of interleukin-2 and -10, interferon-alpha and indicators of leukogram with parasitic infestation, compared to persons without giardiasis. It can be assumed, that high levels of inhalation chemical load, affecting the immune system of adolescents, create the prerequisites for the deficiency of protective mechanisms and the lamblias persistence.

Russian Journal of Infection and Immunity. 2018;8(3):355-360
pages 355-360 views

EFFICIENCY OF APPLICATION OF ISOTHERMAL AMPLIFICATION AT INSPECTION OF PATIENTS WITH WHOOPING COUGH

Pimenova A.S., Borisova O.Y., Petrova M.S., Voronina I.S., Borisova A.B., Shamsheva O.V., Afanasiev S.S., Vlasov E.V., Aleshkin V.A.

Abstract

Purpose: efficiency isothermal amplification (LAMP) at inspection of patients with whooping cough in clinical conditions. Materials and methods. Examination of 262 patients aged from 0 months up to 30 years hospitalized in Infectious diseases clinical hospital No. 1 of the Moscow Department of Healthcare is conducted. Clinical specimens (pharyngeal swabs) were collected according to MR 3.1.2.0072-13. Extraction DNA of B. pertussiswas carried out by means of the АmplyPrime® DNA-sorb-AM. Identification of specific fragments of a genome of B. pertussiswas performed by PCR-real time by means of the АmplySens ® Bordetella Multi-FL set (a comparison method) and by the LAMP with a phoresis and intercalating dye. Results.When using of the optimized method LAMP the DNA of B. pertussisis found at 252 (96.2%) patients. The method was effective at any forms of whooping cough —DNA of B. pertussisis found in all patients with a severe form, in 95.8% of cases — in patients with medium-weight and in 95.3% of cases — in patients with an easy form. The DNA of B. pertussisis found in clinical specimens received from patients on different terms from the beginning of a disease — from 92.3% on the 1st week up to 96% of cases — on the 5 th and more weeks of a disease. The DNA of B. pertussisis found in high percent of cases (96.7–95.9%) and did not depend on acceptance of antibacterial therapy. Children till 1 year are the main age group which is subject to hospitalization at suspicion of whooping cough and in which the highest risk of development of complications and severe forms of a clinical disease. At inspection of 169 children from 0 to 12 months by means of the optimized method LAMP, DNA of B. pertussisit is found in 98.6% of cases in children of patients with whooping cough aged from 0–3 months, in 98.4% of cases — children of 4–7 months and in 94.6% of cases — at children have 8–12 months. The efficiency of detection of DNA of B. pertussisat patients with whooping cough of children aged till 1 year by means of the optimized LAMP method was 97.6%.

Russian Journal of Infection and Immunity. 2018;8(3):361-368
pages 361-368 views

SHORT COMMUNICATIONS

FEATURES OF THE PHENOTYPE AND NAD(P)-DEPENDENT DEHYDROGENASES ACTIVITY IN NEUTROPHIL BY PATIENTS WITH WIDESPREAD PURULENT PERITONITIS IN PROGNOSIS FOR SEPSIS DEVELOPMENT

Savchenko А.А., Borisov A.G., Cherdancev D.V., Pervova O.V., Kudryavtsev I.V., Gvozdev I.I., Moshev A.V.

Abstract

The aim of the study was to examine the features of phenotype and the levels of NAD(P)-dependent dehydrogenases activity of blood neutrophils in the prognosis of abdominal sepsis development in patients with widespread purulent peritonitis (WPP). 50 patients with WPP of community and hospital origin in the pre-operative period were examined. From the 5th to the 10th day of the postoperative period 35 patients (70%) had developed abdominal sepsis, 15 patients (30%) had absence of complications. As controls 67 respect healthy people were examined. The research blood neutrophils phenotype was performed by f low cytometry using a direct immunofluorescence whole peripheral blood. The levels of surface receptor expression was assessed by the mean fluorescence intensity. The NAD(P)-dependent dehydrogenases activity in the blood neutrophils studied using bioluminescence method. It was established that the inflammatory reaction in patients with WPP is characterized by neutrophilia and changes in the phenotype of blood neutrophils. The markers of the subsequent development of sepsis in WPP are less pronounced (in comparison with the indices of uncomplicated patients), an increase in the number of neutrophils, a decrease in the HLA-DR + -cell count against the background of a high level of neutrophils expressing a high affinity receptor for IgG. The patients without subsequent complications had the number of neutrophils with CD23 receptor expression is increased. Metabolism of neutrophils in patients with WPP is characterized by a decrease in the intensity of plastic processes due to low activity of glucose-6-phosphate dehydrogenase and an imbalance in the activity of the enzymes of the mitochondrial compartment. A feature of the neutrophil metabolism in patients with WPP without subsequent development of sepsis is a high activity of anaerobic lactate dehydrogenase reaction and a decrease in the activity of NADP-dependent decarboxylating malate dehydrogenase. The patients with WPP with subsequent development of sepsis had a high level of NAD-dependent out flow of substrates from the tricarboxylic acid cycle on the amino acid exchange reaction via glutamate dehydrogenase which can affect the activity of aerobic respiration of blood neutrophils. The established differences in the phenotype and activity of enzymes in the blood neutrophils in patients with WPP depending on the subsequent development of sepsis determine the possibility of creating a method for predicting the development of complications and developing immunoactive therapy in the postoperative period of WPP.

Russian Journal of Infection and Immunity. 2018;8(3):369-376
pages 369-376 views

INFLUENCE OF THE LECTIN LACTOBACILLUS DELBRUECKII ssp. BULGARICUS ON ACTIVITY OF THE PROCESS OF PHAGOCYTOSIS

Dolmashkina A.S., Gorelnikova E.A., Karpunina L.V.

Abstract

The effect of Lactobacillus delbrueckii ssp. bulgaricus on the activity of macrophages — peritoneal (PMP) and alveolar (AMP), isolated from the body of white mice at 1, 3, 5, 7 days after the introduction of lectin, in the process of phagocytosis of bacteria Staphylococcus aureus 209-P. In the course of the studies, it was shown that by 6 hours the activity of PMP and AMP isolated within 24 hours after lectin administration had increased by 3.4 and 2.9 times. The PMP and AMP, isolated from the mice for 3 days, showed the greatest activity after 6 hours of incubation with bacterial cells in 1.6 and 2 times in comparison with the control. On day 5, PMP and AMP showed the greatest activity by 6 hours in the process of phagocytosis compared with the control, respectively, in 2.2 and 2.4 times. At day 7, only AMP had the highest activity after 30 minutes of incubation with bacteria 1.5 times in comparison with the control in the process of phagocytosis in vitro by S. aureus 209-P. With respect to PMP, no changes were observed compared to the control. The analysis of the obtained data showed that the activity of macrophages isolated from the organism of mice injected with lectin on days 1, 3, 5 significantly differed from the control values at the final stages of the phagocytosis process of S. aureus 209-P. It can be assumed that the lectin interacting with the surface structures of PMP and AMP on the 1st, 3rd, 5th day of the experiment promotes a more short-term process of adhesion of bacterial cells in phagocytosis. To evaluate the specificity of lectin interaction with receptor structures of macrophages, experiments were conducted with a protein that did not have lectin properties-bovine serum albumin-BSA and lectin blocked by specific carbohydrates. It was shown that the phagocytic activity of macrophages in the presence of BSA was similar to control and did not differ significantly from it. BSA did not influence the completion of bacterial phagocytosis by macrophages. When studying the interaction of lectin blocked by specific carbohydrates on the phagocytic activity of macrophages, there was a slight increase in phagocytic activity against PMP, after 6 hours of phagocytosis and a slight decrease after 0.5 hours, 1 hour and 24 hours of phagocytosis. For AMP, the lectin blocked by a mixture of carbohydrates was similar to the control values. The results obtained made it possible to speak of the specific binding of lectin L. delbrueckii ssp. bulgaricus with surface AMP receptors. However, with respect to PMP, a small activity of macrophages in the process of phagocytosis was observed, which indicates the specific and non-specific binding of lectin L. delbrueckii ssp. bulgaricus with surface TMF receptors. It can be assumed that, at the molecular level, L. delbrueckii ssp. bulgaricus, in addition to a specific interaction with the receptor structures of PMP, can participate in a variety of nonspecific reactions. Thus, the lectin L. delbrueckii ssp. bulgaricus increased the adhesive ability of macrophages of mice, significantly influenced the completeness of the phagocytosis process of bacterial cells. A specific interaction of L. delbrueckii ssp bulgaricus with surface AMP receptors, both specific and non-specific interactions were observed with respect to PMP.

Russian Journal of Infection and Immunity. 2018;8(3):377-382
pages 377-382 views

IMPACT OF COINFECTION OF PV B19 ON THE COURSE AND PROGNOSIS OF MALARIA CAUSED BY PLASMODIUM FALCIPARUM

Lavrentyeva I.N., Khamitova I.V., Slita A.V., Levkovski A.E., Diallo A.A., Diallo A.K., Sow T.C., Naydenova E.V., Agafonov D.A., Senichkina A.M.

Abstract

Parvovirus infection (PVI) is widespread in the world; more than 80% of the adult population have antibodies of IgG class to parvovirus B19. Malaria is a vector-borne parasitic disease caused by the protozoa of the genus Plasmodium, that is widespread in the countries of Africa, Southeast Asia, Oceania. The objective of the present study was to evaluate the effect of parvovirus B19 infection on the clinical course of malaria and the outcome of the underlying disease. During the period 2016–2018 blood plasma samples of 316 patients from the hospital of the Friya Prefecture of the Republic of Guinea (GR) with confirmed diagnosis of malaria were examined for the presence of PVB19 DNA. The clinical course of malaria in 316 examined patients was divided into group of either mild or complicated. In total, PVB19 DNA was detected in blood plasma in 55 of 316 patients (17.41±2.13%). But in the group with co-infection of PVB19 and P. falciparum complications were observed in 40 of 55 (72.73±2.75%) patients, and in 6 of 55 cases (10.91±4.40%) the disease resulted in death. In the group of patients with malaria without PVI, complications occurred in 99 of 261 patients (37.9±3.0%); of those 2 (0.77±0.54%) died. It was found that the most numerous group in the structure of malaria patients is represented by children under 5 (median 3) years (89, or 28.25±2.53%). Our results correlate with the data of other researchers who studied the PVI-associated malaria in children in malaria-endemic regions: among children under 5 years, the absolute majority of cases of PVI was accompanied by a complicated course of malaria. The primary parvovirus infection can aggravate the course of malaria, especially when combined with other unfavorable conditions (iron deficiency, malnutrition, helminthic infections, co-infections, etc.). Thus, infection with PVB19 becomes a critical factor, which can provoke a severe life-threatening anemia, and also cause other complications.
Russian Journal of Infection and Immunity. 2018;8(3):383-387
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COMPLIANCE OF ANTHRAX RECOMBINANT VACCINE PROTOTYPE WITH THE REQUIREMENTS TO IMMUNE-BIOLOGICAL PREPARATIONS

Mikshis N.I., Semakova A.P., Popova P.Y., Kudryavtseva O.M., Bugorkova S.A., Komissarov A.V., Germanchuk V.G., Popov Y.A.

Abstract

Current areal of anthrax among live stock and wild animals covers almost all the continents. The cause of human infection is conventionally considered to be the contact with diseased animals in the process of carrying for an animal, forced slaughter or further trimming of carcasses, as well as contact with infected raw materials of animal origin. Licensed vaccines has made an invaluable contribution to the improvement of epidemiological situation on anthrax, however, development of the vaccines complying with current scientific progress remains relevant. We have constructed a vaccine prototype containing recombinant protective antigen and S-layer EA1 protein and added state-of-the-art CpG 2006 adjuvant to the formulation. We have demonstrated the advantage of the lyophilized form of the preparation. Objective — obtainment of anthrax vaccine prototype in lyophilized state and assessment of the prototype compliance with the requirements to vaccine preparations. Materials and methods. Isolation of rPA and EA1 protein was carried out using producer-strain B. anthracis 55ΔTПА-1Spo– on an integrated end-to-end manufacturing line, including concentration, diafiltration and two-phase chromatography. CpG 2006 adjuvant was synthesized according to known sequences. Components were mixed and lyophilized in sublimation unit. Combination of 1% sucrose and 3% glycine was used as cryoprotector. Effectiveness and safety of the preparation were evaluated on the model of BALB/c mice and guinea pigs applying immunological, morphometric, and histological assays. Antibody titers in sera of immunized animals were evaluated using standard ELISA procedures. Protective properties were investigated through LD50 values for the test-strain used on immunized and control animals and immunity index. Results. We have performed complex investigation of the anthrax vaccine prototype, containing B. anthracis 55ΔTПА-1Spo– proteins as main and supplementary antigens, as well as CpG 2006 adjuvant, stabilizers and preservative agent. The prototype meets the requirements to immunobiological medicinal drugs by all physical-chemical properties. Our preparation does not have a toxic effect on the organism of laboratory animals in case of subcutaneous and intraperitoneal administration of single human dose. Pathomorphological study of guinea pigs’ organs immunized with double dose of the vaccine prototype has not revealed any evidence of damaging effect on the cells and tissues of macroorganism. The prototype protects BALB/c mice from the infection with B. anthracis 71/12 test-strain.
Russian Journal of Infection and Immunity. 2018;8(3):388-392
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INSTRUCTIONS TO AUTHORS

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Russian Journal of Infection and Immunity. 2018;8(3):393-395
pages 393-395 views

AUTHOR INDEX

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Russian Journal of Infection and Immunity. 2018;8(3):396
pages 396 views

SUBJECT INDEX

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Russian Journal of Infection and Immunity. 2018;8(3):396
pages 396 views

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