Vol 8, No 1 (2018)

Numerous modern basic research done undeniable fact that neutrophilic granulocytes (NG) are key effector and regulatory circuits both innate and adaptive immunity, and play a crucial role in the pathogenesis of a wide range of diseases. NG have potent receptor repertoire, providing a connection between them, cells of the immune system, as well as communication with endothelial cells, epithelial and other tissues. NG inducing stimuli activate and promote the translocation of cytoplasmic granules and vesicles surface molecules on the cytoplasmic membrane the secretion of a large spectrum of pro-and anti-inflammatory, immunoregulatory cytokines, colony, angiogenic factors and fibrogenic, TNF superfamily members, chemokines, regulatory protein, etc. Chromatin nuclei NG capable of restructuring under the influence of inducing stimuli, which is associated with the expression of multiple cytokine genes. NG receiving complex cytokine influence not only acquire new features, but also in various stages of activation and differentiation processes involved in intracellular intraphagosomalis degranulation and killing of implementing elimination microorganisms and extracellular neutrophil degranulation in the formation neutrophil extracellular traps (NET), while this dying through NETosis. Features NG phenotype and their functional properties, demonstrate the existence of subpopulations of NG with different capabilities: equipment of different receptor, the ability to restructure chromatin expressing cytokine genes and secrete cytokines to implement the contents of the granular system, produce reactive oxygen species, implement cytotoxicity form NET. In our opinion, there subpopulation NG: regulatory; suppressor; proinflammatory — initiating an inflammatory response; inflammation with a positive potential microbicidal (antibacterial, antiviral, antifungal); inflammatory cytotoxic potential of the negative — «aggressive»; anti-inflammation regulating regression; antitumoral — TAN1; pro-tumoral — TAN2; hybrid, combining the characteristics of NG and dendritic cells. The absence of adequate response, or hyperactivation blockade NG functions leads to the development of low-intensity infectious and inflammatory diseases, do not respond to conventional therapy of autoimmune diseases/chronic immune-dependent processes. Remo deling dysfunctions NG — the key to new immunotherapeutic strategies.

Macrophages (Mf) play an important role in the pathogenesis of influenza infection, but the obtaining of Mf in large quantities is difficult. In connection with this, in the present study, THP-1 monocytes differentiated by phorbol ether (PMA) into macrophages (MF) were used to study influenza infection. Differentiated cells — THP-PMA Mf were infected with pandemic А(H1N1)pdm09 and avian influenza A viruses H5N2 and H9N2. Differences in the levels of penetration of viral RNA (gene M1) and nucleocapsid (NP) proteins of the investigated viruses were found. The levels of expression of viral RNA and proteins were significantly higher in cells infected with avian viruses compared to pandemic viruses. Of particular interest is the phenomenon of prolonged intracellular presence of viral RNAs and nuclear localization of NP protein. However, no infectious or haemagglutinating activity of the virus of all subtypes studied in the culture liquid was detected up to 96 h. This indicates the abortive nature of influenza infection in THP-PMA Mf. Thus, MF performs a special function of depositing viral components and delivering them to the sites of inflammation. The blocking mechanism in human and avian influenza A viruses with different pathogenicity may differ, due to the existence of multiple mechanisms of escape from the immune response. As a result of infection with the human virus А(H1N1)pdm09, the infection developed slowly and caused death of 25% of the cells by 72 h, whereas in the case of infection with avian viruses, 50% of the cells died after 24 hours and by 72 h all the THP-PMA MF died. Preprocessing with recombinant IFNα2b had a protective effect, suppressing the accumulation of the NP protein of the A/H5N2 virus in the THP-PMA Mf nuclei. The obtained data allow us to conclude that one of the reasons for the different course and outcome of influenza infection in human infection with influenza A viruses is the sensitivity of human macrophages to avian influenza viruses of subtypes H5 and H9 as compared to the pandemic virus. Our result on the THP-PMA Mf model is consistent with reports on the blocking of the stages of the release of infectious influenza A virions in primary cultures of monocytic and alveolar MF. Massive death of MF caused by avian influenza viruses explains their high pathogenicity.

Maintenance of thermo homeostasis under the coordinating influence of the hypothalamus is ensured by integrative interaction of various systems organisme, including the immune system. Temperature stress in infectious diseases activates the reaction of heat shock, the biochemical consequence of which is the initiation of the organism’s defense against the pathogen. Cells of innate immunity (neutrophils and macrophages) are the first line of protection against pathogenic agents and play a primary role in the development of bacterial infections. Of particular interest is the study of the duration of the effect of hyperthermia to achieve a balance between the bioenergetic costs of these cells, as well as the study of the course of the pathological process in an organism previously exposed to hige temperature. The functional status of neutrophils and macrophages, including phagocytosis, the activity of enzymes of the oxygen-dependent system: lactate dehydrogenase, cytochrome oxidase, myeloperoxidase, cellular stimulation (intracellular AMPase content) and the content of nitrogen oxide metabolites have been studied in the model of animals exposed to low and high temperatures. It has been established that under hyperthermia conditions, the change in the functional activity of cells by enzyme level is more pronounced than when exposed to animals with low temperature, especially 4 h exposure. In animals pre-exposed to heat stress, manifestations of pseudotuberculosis infection were more severe with an increase in mortality rates by 2.6 times, compared to animals infected by bacteria. These animals had a high stimulation of effector cells of inflammation in the initial periods (at 7 days) their metabolism was enhanced, which was expressed of the activity of enzymes of the oxygen-dependent system, as well as in high nitroxide-producing activity. In target organs (lung, liver, spleen) of experienced animals the severe disturbance of blood circulation in combination with significant destructive changes typical for generalized infection were showed. At dead animals on the background of marked hemorrhagic component pathological process and weak cell inflammatory response observed depletion of the immune system (delimphatization), indicating a decrease in defense reactions and the development of immunodeficiency. Thus, under conditions of heat stress (+30°С), the intensity of the reaction of innate immunity cells in terms of enzyme’s functional activity was higher than when exposed to animals of low temperature (+4°C). Under these temperature conditions, a high level of cell priming was determined, which reduced their killing potential. These data indicate the adequacy of the model used to reproduce induced secondary immunodeficiency in a congenital defense system. Moreover, in the pathogenesis of pseudotuberculosis infection against the background of prolonged action high temperature, the effects of phagocytes oxidative stress in the structural changes of immunocompetent organs were detected.

Wide migration processes typical for megacities, including St. Petersburg, require a comprehensive study of the infection among migrants arriving on a work visa. Biological material for research was taken from 370 migrants who arrived in St. Petersburg on a work visa. The control group is represented by 320 adults of St. Petersburg. The methodology of the study of the biological material depended on the type of pathogen and included classical and modern methods of research. All obtained data are processed using adequate methods of mathematical statistics. C. diphtheriae strains in migrant workers were isolated 80 times more often than in permanent residents of St. Petersburg. In St. Petersburg gravis biovar occurs in 25% of cases, in the visiting contingent — in 83% of cases, which is an unfavorable prognostic sign. In migrants 17% of C. diphtheriae strains have a “silent” gene (tox+), which, under known conditions, can resume toxin production. The local people are protected from diphtheria by 95%, and labor migrant is only 66%. 17% of migrant workers with C. diphtheriae strains have a low level of protection against diphtheria, which poses a threat to them and those in contact with them. Infection with brucellosis pathogens of labor migrants from Uzbekistan is 9 times higher than the local population, persons from Tajikistan — 60 times higher. The infection rate of migrant workers from Uzbekistan and Tajikistan C. burnetii is 25 times higher than that of the local population. The chronic course of these infections complicates diagnosis and reduces the quality of life. According to the results of the screening test, S. Typhi bacterium carrier is distributed 7 times more in migrant workers from Uzbekistan and 2 times more in persons from Tajikistan than among the local population of St. Petersburg. The seroprevalence of toxic H. pylori in migrant workers is 84%, which is much higher than that of permanent residents of St. Petersburg (57%). The causes of this phenomenon have not been studied and require further study. Labor migrants from Central Asia have a low level of population immunity to parvovirus infection: 37% of seropositive persons from Uzbekistan and 62% from Tajikistan compared with 78% of the local population. This may contribute to the spread of parvovirus infection involving infection of seronegative residents of St. Petersburg risk groups, including blood donors, pregnant women, persons with immunodeficiencies, hematologic and oncologic patients. The results obtained ascertain the tense epidemiological situation among labour migrants in St. Petersburg for a number of infections. Reliable information will help to organize the correct further study of the problem and conduct appropriate measures to preserve the health of the local population and the visiting contingent.

Susceptibility to 16 antimicrobial agents in 421 Klebsiella pneumoniae strains, isolated in a multidisciplinary medical centre from patients with nosocomial infections in 2015, was tested. The majority of studied strains were resistant to antibiotics: ampicillin/clavulanic acid (91.4%), ticarcillin/clavlanic acid (81.9%), piperacillin/tazobactam (69.4%), fluorochinolones (83.6%), III and IV generation of cephalosporines (79.8%), gentamycin (72.9%); one third (34.2%) demonstrated resistance to amikacin. K. pneumoniae strains demonstrated high level of carbapenem resistance (53.0% — to ertapenem, 42.8% — to meropenem and 37.1% — to imipenem), associated resistance to at least 3 different classes of antibiotics — caphalosporins, aminoglycozides, fluorochinolones, that amounted to more than half of the strains (57.7%), including 44.2% of the strains, additionally resistant to carbapenems. The lowest level of resistance was found to fosfomycin (8.5%) and tigecycline (7.4%), resistant cultures showed intermediate resistance with MIC 2 μg/ml to the latter. High diversity of antimicrobial resistance spectra was found, with high level of multidrug resistant strains (87.2%). Resistance to carapenems in K. pneumoniae isolated in the multidisciplinary medical center was determined by either bla_OXA-48 (59.3% of isolates, resistant to carbapenems) or bla_NDM-1 (40.7%).

February 14^th 2018 —  anniversary of the famous scientist, academician of the USSR Academy of Medical Sciences, great immunologist and microbiologist Vladimir Ilyich Ioffe the founder of the Russian school of clinical and epidemiological immunology. He created an authoritative Scientific School, anticipated many concepts of infectious immunology, justified and linked together theory, experiment and practical implementation of 3 fields of science: microbiology, immunology and epidemiology thus providing a fertile ground for breakthrough in infectious pathology. Ioffe has developed the principles of quantitative analysis of processes, created the methodology of titer tests to evaluate the strength of the body's defense system or organism allergization. His works have proved long before foreign scientists that scarlet fever and rheumatic fever were streptococcal infections, introduced immunogram as clinico-immunological characteristic of the patient’s disease, and reflected the patterns of disease development and manifestation. Ioffe’s publications provide comparative characteristics of experimental, clinical and epidemiological immunology as independent immunological scientific areas with its own content, aim and subject of research. Based on the wealth of experimental, clinico-immunological and epidemiological data Ioffe created such fundamental works as “Clinical and Epidemiological Immunology”, “Scarlet Fever”, “Whooping Cough”, “Immunology of Rheumatism”, which are still in the researchers’ focus of attention.