[Cow colostrum: component composition, biological properties and application practice].

Bovine colostrum (ВС) has a high biological value, which allows it to be used for the development of new functional products. The aim of the study was to assess the possibility of using BC for the prevention and treatment of infectious and non-infectious diseases. Material and methods. The search for scientific information on the study of the component composition, immunobiological properties and the use of BC in clinical practice was carried out using the databases of the RSCI, CyberLeninka, ScienceDirect, PubMed. Results. The macro- and micronutrient composition of BC is presented, its changes over time from the moment of calving are described. A comparative analysis of the content of various components in milk and colostrum is presented. A detailed list of antimicrobial factors that increase nonspecific resistance and provide immunocorrective, antimicrobial and anti-inflammatory effects is submitted. The possibility of using BC in clinical practice as a part of complex therapy in the treatment of various infectious diseases, including severe acute respiratory syndrome caused by the new coronavirus infe ction SARS-CoV-2, as well as in cardiovascular diseases, allergies, autoimmune and oncological diseases, has been demonstrated. Conclusion. According to the literature, BC has a high safety profile and is applicable to all age groups of the population. Given the wide range of biological activity of BC components, a promising area of scientific research is the development of the products for therapeutic and prophylactic purposes, including dietary supplements, based on its ingredients, which have the desired properties for correcting the immune status, preventing non-communicable and infectious diseases, as well as for prevention of occupational diseases among persons working in harmful working conditions.

Comparative tests of quality of bacteriological investigation with Corynebacterium diphtheriae isolation.

The results of comparative experimental studies of identification of nontoxigenic C. diphtheriae strain by three different commercial laboratories are presented. A typical nontoxigenic strain of C. diphtheriae biovar mitis was used. For the studies, three lines of ten-fold dilutions of bacterial culture were prepared, followed by control planting on the medium and counting CFU/ml. In the experiment, tampons were pooled with a 24-hour bacterial culture of a nontoxigenic C. diphtheriae strain. Tampons were provided from three different laboratories - ∑-Transwab® with Ames liquid medium (from the first and second laboratories) and a viscose tampon with coal medium (from the third laboratory). After pooled, tampons were delivered to commercial laboratories. And as a result of the experiment, Corynebacterium spp. was identified in first laboratory (103 CFU/tamp), S. epidermidis (102 CFU/ml) - in second laboratory and nontoxigenic C. diphtheriae biovar gravis - in third laboratory. The study indicates that there is a need to the supervision of bacteriological investigations conducted in various laboratories. This will improve the quality of investigations on diphtheria infection and identify of diphtheria carrier, which is a reservoir of the causative agent of diphtheria, and will contribute to the maintenance of sanitary and epidemiological well-being in our country.

Digital analysis and quantitative assessment of the cervical surface with dysplasia.

The investigation aims - a quantitative assessment of cervical surface changes with digital analysis and computer technologies in dysplasia. Colposcopy was made in 90 women from 21 to 52 years (avr. age 33,9±8,13 y.o.) with mild epithelial dysplasia (CIN1), moderate dysplasia (CIN2), severe dysplasia (CIN3). The algorithm detected indicators which provide the cervical dysplasia classification on pre cytological and pre molecular-genetic patients investigations. The outcome of an algorithm was the identification of the cervix surface condition severity by an objective quantification. The cervical dysplasia type (CIN) was classified as IndGV values. The mild dysplasia (CIN1) had IndGV=8,5, moderate dysplasia (CIN2) - IndGV=13, severe dysplasia (CIN3) - IndGV=15,6. The cervical affected surface area (IndInt) equalled 0,17 in CIN1, 0,19 in CIN2, 0,22 in CIN3. A change severity has a direct relation with a grey color value. It demonstrates quantify classification in digital analysis. The algorithm is used in real-time mode and no requires considerable material outlays. This makes it possible to use an algorithm after clinical examination and predict patient management.

PCR-based diagnosis of whooping cough in the Russian Federation.

The aim was to determine how often the PCR method is used in different laboratories in Russia. In 2018, we conducted a questionnaire survey in diagnostic laboratories of medical organizations and the Centers of Hygiene and Epidemiology that performed PCR studies to identify microorganisms of the genus Bordetella in all 85 Russian regions. We found that in 2013 the PCR was used in 33 (38.8%) regions, but in 2017 the number of regions increased to 64 (75.3%). During 2013-2017 the study has not been applied in 21 regions. The number of PCR tests performed in the laboratories of medical organizations was significantly different. There has been an increase in the number of tests for the diagnosis of pertussis among people with clinical signs of infection and among contact persons in foci of infection. Compared to the Centers of Hygiene and Epidemiology, in medical organizations the rate of introduction of the PCR was higher. Between 2013 and 2017 the proportion of samples containing DNA B.pertussis decreased, but the proportion of samples containing DNA of other representatives of the genus Bordetella increased. Moreover, in the case of isolation DNA Bordetella spp. clinicians diagnose «Whooping cough, other unspecified organism¼, since there is no information on the species of the pathogen. Thus, in order to improve the diagnosis of pertussis, it is necessary to optimize PCR tests by including target genes that allow to identify of currently relevant DNAs of different representatives of the genus Bordetella.

Status and problems of bacteriological diagnosis of diphtheria infection in the Russian Federation.

The purpose of the work was to assess the state of bacteriological diagnosis of diphtheria infection in Russia in order to establish possible reasons for the decrease in the release of C. diphtheriae. The Reference Center for Monitoring the Pathogens of Measles, Rubella, Mumps, Pertussis and Diphtheria in 2018 in 85 subjects of Russia conducted a questionnaire of laboratories of medical organizations and the Centers for Hygiene and Epidemiology of Rospotrebnadzor, carrying out bacteriological studies for diphtheria infection. It was found that the number of studies conducted over the five-year period decreased by 1.2 times. The tendency to decrease the number of bacteriological studies for diphtheria is observed in the territories of almost all federal districts. In 99% and 29% of cases, the institutions of the FBUZ Centers for Hygiene and Epidemiology and medical organizations (MO) and use in their work documents regulating bacteriological studies for diphtheria infection. In a number of territories, the list of documents used includes documents that are invalid or do not define such studies. Most organizations use dry tampons when examining for diphtheria, however, 13.1% and 53.4% of FBUZ Centers for Hygiene and Epidemiology and medical organizations (respectively) use commercial transport environments, which does not comply with regulatory documentation. Analysis of the quality of work of bacteriological laboratories showed shortcomings at the stage of preparation of media (use of donor blood, or absence of addition of blood and potassium tellurite), Elek tests (addition of horse serum or absence of serum to the medium), setting of incomplete biochemical series (absence of tests for urease and nitrate reductase), absence of standard control strains, incomplete volume of internal laboratory quality control. Given the continuing circulation of the pathogen in various countries of the world and in our country, as well as the possibility of imported cases of infection from endemic regions, the analysis was aimed at drawing the attention of specialists to the problem of improving the quality of laboratory diagnosis of diphtheria in Russia.

[The human lectin supersystems possessing probiotic and protective actions.]

The potential of useful for human immunobiological supersystems of lectins (SSL) recognizing carbohydrates and glycoconjugates of molecular or supramolecular protein/(oligo)peptide-containing constituents of biotopes is described. SSL recognize, reversibly bind, delivery to biotopes, orient natural or synthetic polymeric, polyvalent glycoconjugates (imitators of natural glycopolymers) at the cell surface. The key features of SSL are indicated and described. The possibilities of application and prospects of SL of probiotics, complement С4 system and protein hormones (on example of erythropoietins) in prognostics and diagnostics of pathologies, prophylaxis and therapy of diseases and medical biotechnology are evaluated.

[Lectin populations of NK cells against tumors coupled to viral infections (review of literature).]

Analysis of the human NK (natural killers) cells and their functionally different populations in connection to tumor processes accompanied with viral infections is presented. Receptor lectins (non-immunoglobulin proteins and their complexes recognizing polysaccharides, glycoconjugates and glycopattern-containing molecules) play important role in regulation of innate immunity. Communicative diversity of NK-cell populations (in which lectins cofunction to other receptors) is directed against tumors and viruses. Effectiveness and selectivity of action of NK cell populations can be increased in cooperation together with adaptive immunity. Evaluations of occurrence, redistribution (also under influence of cytokines) and contribution of NK-populations (depending on lectin receptors recognition coupled to multifunctions of receptors) in respect of increasing antitumor and antiviral immune responces are given. The data indicate extended prospects of lectin receptors (coupled to other type receptors) containing NK populations of the network compartment of innate immunity upon realization of different variants of organism protection in cooperation with cellular and humoral immunity. Such NK populations are the basis for further intercellular interactions. Innate immunity Cross-Talk, involving the leader NK cell populations acting according to humoral immunity mechanisms, acts on duty regime (importance for therapy of chronic pathology) that results in providing optimal combined antitumor and antiviral cytokine and cytotoxic responses according to the principle of action as «network-in-network¼. The influence network of lectin, Ig-like, cytotoxic, other regulator NK populations (also throuph redistribution of production of cytokines by immunocompetent cells) is perspective for forming early prolongated antitumor and antiviral processes of different types in organism. It is of importance to consider CD diversity of receptor repertuar of lectin, Ig-like and other NK populations revealing different ontogenesis as well as to seach patient key NK-populations to select and construct personally (or for contingents in cases of epidemiological significance) optimal therapeutic/prophylactic NK populations (like variants of CAR-T). Aforementioned data indicate perspectiveness of NK cell populations in development of new antitumor/antiviral effective and selective vaccine strategies, preparations and regimes of their applications. Probiotic lectins reveal features of perspective ligands cofunctioning to network of NK cell populations.

[Lectins and glycoconjugates in presentation of antigens and protection against patogens.]

The current data on using lectin receptors and glycoconjugates (GC) in study of pathways of intercellular communications within innate immunity network coupled to adaptive immunity wеre overviewed and systematized. A superfamily of GC-specific C-type lectin receptors (CLR), as a constituent of pattern recognizing receptors (PRR), involves in immunity to produce redistribution of groups of cytokines, chemokines and specific antibodies. CLR on surface of multiple subpopulations of antigen-presenting cells (APC) and other cells of immunity are under consideration (monocyte derived macrophages, macrophages, immature and mature dendritic cells, other myeloid cells, neutrophils, basophils, lymphocytes, etc.). CLR cofunction both each other and/or together with other PRR and immune receptors. CLR are favourable for quicker and GC-specific innate type presentation of important danger antigenic patterns (PAMP, MAMP, DAMP, SAMP, TAMP) using their specific targeting through currently/ adaptively optimal pathways within intercellular branched network of activated/ polarized subpopulations of cells mentioned above. CLR agonist GC (recombinant, synthetic, conjugates to carriers (adaptive proteins, etc.), assembled into nanoparticles and liposomes) can serve successful and specific adjuvants in vaccine strategies. CLR and GC pairs participate in on duty biocontrol of immunobiological supervising in organism, modulate/ switch recognition and protection cell pathways of immune responses (presentation, reciprocally organized protective attacks, rates and amplitudes of activation and inhibition of cell communicative chains). Lectins characterized both cell and cell communicative chain current functional biomarkering that is of importance for clinical diagnostics. The knowledge on CLR-GC pattern relationships is perspective for study and influence fine mechanisms of cell GC-targeting and immunity, improvement of traditional vaccines, development of GC-specific and highly effective pattern vaccines against different infections or tumors. New specific vaccine strategies are possible towards different biotopes in organism (also for mucosal opened cavities).

[COMPLEX IMMUNOGLOBULIN PREPARATION FOR THERAPY OF PERTUSSIS IN YOUNG CHILDREN].

AIM: Study the possibility of inclusion of complex immunoglobulin preparation (CIP) pos- sessing specific activity against pertussis exotoxins into complex therapy of pertussis infection in young children. MATERIALS AND METHODS: -2 groups of children with.pertussis younger than 3 years were examined. The main group (50 individuals) received CIPper os - 1 dose 1 - 2 times per day for 5 days, comparison group (34 children) received only basic therapy. Evaluation of clinical effectiveness of CIP was carried out, the content of anti-pertussis class G antibodies and total IgE in patients were studied. RESULTS: A good clinical effectiveness of the preparation was shown, as well as immune modulating activity against humoral immune response to pertussis infection. CONCLUSION: The detected positive effect of CIP on pertussis -course in children has indicated a principally novel use of this per oral drug form.

Phagebiotics in treatment and prophylaxis of healthcare-associated infections.

We have developed a phagebiotic composition using 8 virulent bacteriophages (2 strains of each species) which are able to lyse Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. The unique character of the developed composition is ensured by particular properties of each bacteriophage comprising the preparation, including their range of lytic activity toward specific bacterial pathogens, morphology of their plaques, cycle of their development, restriction profile of their DNAs, specificity of their genomes (based on complete genome sequencing), and other properties. The preparation did not produce any signs of acute or chronic intoxication in the experimental animals. Therapeutic and prophylactic efficiency of the phagebiotic composition was demonstrated in the prevention and treatment of the experimental acute K. pneumoniae infection in mice. The investigations have shown that the preparation possesses a high therapeutic efficiency and is highly competitive with ciprofloxacin which is very effective against the infective strain K. pneumoniae. Our small-scale clinical trial was aimed to evaluate therapeutic effectiveness of the phagebiotic composition in an epidemiological emergency situation in an intensive care unit, caused by multi-resistant strains of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Seventy nine per cent of the initial samples from 14 patients' endotracheal aspirate, blood and urine were contaminated. Twenty-four hours after the 3-day phage therapy (20 ml of cocktail at a titer for each phage 108 pfu/ml were introduced intragastrically through a tube once a day) contamination level dropped to 21%. Hence the obtained results enabled us to create a new phagebiotic composition that may be used as an alternative to antibiotics to treat these healthcare-associated infections.

[The clinical markers of infection of bloodstream in out-patients].

The sampling of270 out-patients was examined to detect principal clinical symptoms under infection of bloodstream. The principal clinical symptoms the form of complaints were collected using specially developed questionnaire. The patients mentioned most frequently low-grade fever, shivering, furuncles of skin, unstable stool (diarrhea or constipation), diseases of upper respiratory ways. The microbiological diagnostic of infection of bloodstream included microscopy and inoculation of leukocyte layer of blood sample. At microscopy of blood smears microorganisms were detected in 98.5% of cases. The positive findings were presented by associations of various morphological forms in 82.6% of cases. The hemoculture was obtained from 55.2% of patients and characterized by polymicrobility in 35.7% of cases. The greatest number of hemoculture were obtained from patients with low-grade fever and shivering (53.4%), furuncles (55.8%), unstable stool (53.6%), diseases of upper respiratory ways (53.8%) that substantiate presence of infection of bloodstream.

[PROBLEMS TOWARDS MEASLES ELIMINATION IN RUSSIAN FEDERATION].

Introduction of live measles vaccines into daily practice resulted in a pronounced reduction of measles morbidity in many countries, that allowed WHO to develop the measles eradication program. Russian Federation has commenced realization of the eradication program for local measles cases in the country, (measles elimination) in 2002. and had achieved significant success by 2007. For 4 years (2007 -2010) the parameter of measles morbidity in Russian.Federation did not exceed the WHO measles elimination criteria - no more than 1 measles case per 1 million population. However, the situation for measles began to deteriorate from 2011, reflecting the growth of measles morbidity in many regions of the world. The main reason for measles morbidity growth was accumulation of a contingent,of individuals not immunized against measles against the background of internal and external population migration. Under the condition ofconstant maintenance of a high vaccination coverage of the population (above 95%) on thewhole territory of Russia, the objective of measles elimination in the country can be successively met.

[COMPOSITION OF POPULATION OF DIPHTHERIA CAUSATIVE AGENT STRAINS IN RUSSIA].

AIM: Characteristics of clonal composition of Corynebacterium diphtheriae strain population in Russia using MLST, as well as evaluation of a possibility of using of this method during execu- tion of monitoring of diphtheria infection causative agent strains. MATERIALS AND METHODS: C. diph- theriae strains, isolated in Russia in 1957 - 2015 and sent to Gabrichevsky MRIEM reference centre for diphtheria and pertussis, were studied. Gentyping of C. diphtheriae using MLST was carried out based on sequencing of <> gene fragments. ST identification was carried out according to PubMLST Result. C. diphtheriae strains of 36 sequence-types (ST) were identi- fied on the territory of Russia - 27 previously known and 9 novel, detected for the first time. 2 sequence types ST25 and ST8 (22% and 18%) dominated. Inter-relation between phenotype. properties (toxigenicity. and biovar) and membership of C. diphtheriae strains in certain sequence- types was shown - toxigenic and non-toxigenic C. diphtheriae strains of various biovars were characterized by certain sequence-types. Changes of clonal composition of C. diphtheriae popula- tion in dynamics of epidemic process of diphtheria infection were.shown. CONCLUSION: Use of MLST allowed to characterized clonal composition of C. diphtheriae strains' population in Russia and has shown perspectives of use of this method to characterize population of diphtheria causative agent, detect epidemically significant strains and decipher foci of diphtheria infection.

[THE CONDITION AND TENDENCIES OF DEVELOPMENT OF CLINICAL AND SANITARY MICROBIOLOGY IN THE RUSSIAN FEDERATION AND PROBLEM OF IMPORT SUBSTITUTION].

The import substitution becomes one of the strategic tasks of national economy as a result of prolongation of economic sanctions concerning the Russian Federation of part of the USA, EU countries, Japan and number of other countries. It is not proper to be limited in import substitution only by goods because in conditions ofsanctions when access toforeign technologies is complicated Russia is needed to substitute foreign technologies by national designs in faster manner One of directions of effective import substitution is localization of production of laboratory equipment and consumables for clinical and sanitary microbiology on the territory ofthe Russian Federation and countries of Customs union. In Russia, in the field ofdiagnostic of dangerous and socially significant infections, all components for import substitution to implement gene diagnostic, immune diagnostic. bio-sensory and biochip approaches, isolation and storage of live microbial cultures, implementation of high-tech methods of diagnostic are available. At the same time, national diagnostic instrument-making industry for microbiology is factually absent. The few devices of national production more than on 50% consist of import components. The microbiological laboratories are to be equipped only with import devices of open type for applying national components. The most perspective national designs to be implemented are multiplex polimerase chain reaction test-systems and biochips on the basis of national plotters and readers. The modern development of diagnostic equipment and diagnostic instruments requires supplement of national collections of bacterial and viral pathogens and working-through of organizational schemes of supplying collections with strains. The presented data concerning justification of nomenclature of laboratory equipment and consumables permits to satisfy in fill scope the needs of clinical and sanitary microbiology in devices, growth mediums, consumables of national production and to refuse import deliveries without decreasing quality of microbiological analysis. This approach will ensure appropriate response to occurring challenges and new biological dangers and maintenance of biosecurity of the Russian Federation at proper level.

[THE ACTUAL APPROACHES TO PROBLEM OF IMPORT SUBSTITUTION IN TH FIELD OF PRODUCTION GROWTH MEDIUM].

The import substitution becomes one of strategic tasks of Russian economy as a result of imposition of economic sanctions on part of the USA, EU countries, Japan and number of other states. The development of structure and technology of production of national import substituted growth mediums permits satisfying needs of laboratory service of Russia inactive storage and to secure appropriate response to occurring challenges and new biological menaces and support bio-security of state at proper level. The presented data concerning substantiation of nomenclature of growth mediums and transport system permit satisfying in fullness the needs of clinical and sanitary microbiology in growth mediums of national production and to give up of import deliveries without decreasing of quality of microbiological studies.

[Quantitative and qualitative composition of axilla microbiota in practically healthy individuals].

AIM: Characteristics of quantitative and qualitative composition of cultured microorganisms isolated from axilla skin of practically healthy individuals. MATERIALS AND METHODS: 77 practically healthy individuals aged 18 to 40 years were examined. Species identification of microorganisms was carried out byculture-morphologic, tinctorial and biochemical properties using time-of-flight mass spectrometer and rpoB gene amplification with subsequent direct sequencing. RESULTS: Quantitative evaluation of microbial composition of axilla skin microbiota in most of the practically healthy individuals varied in the 4-5 lg CFU/ml interval, whereas seeding of skin by this microbiota at the level of 8 lg CFU/ml was not detected. 158 strains of 24 microorganism species were identified in this biotope. Most of these strains (68.9%) belonged to Corynebacterium genus, 21.6% of strains--to Staphylococcus genus, 7.6% of strains--to Micrococcus genus and 1.9% of strains--Candida albicans. 16 species of corynebacteria were isolated with predomination of C. tuberculostearicum (40.3%), C. amycolatum (18.4%) and C. ureicelerivorans (14.8%) strains. The microbial landscape in most of the examined individuals (77.9%) was presented by microorganism association. CONCLUSION: Quantitative and qualitative species composition of cultured microorganisms isolated from axilla skin biotope of practically healthy individuals was characterized for the first time.

[Activity of B and D factors of complement alternative pathway in children with atopic dermatitis].

AIM: Development of enzyme immunoassay detection of B and D factors of complement alternative pathway functional activity for solving diagnostic and prognostic problems of patient therapy. Study activity of these factors in blood sera of children with atopic dermatitis before and after therapy for elucidation of the role of complement alternative pathway in pathogenesis of this disease. MATERIALS AND METHODS: Children aged 6 months to 18 years with atopic dermatitis were examined for functional activity of B and D factors in blood sera before and after therapy by the developed methods. RESULTS: The developed enzyme immunoassay methods for determination of functional activity of B and D complement alternative pathway showed high sensitivity and reliability. In children with atopic dermatitis factor B and D activity was significantly lower than normal before treatment. After treatment these activity increased significantly (p < 0.004) and in the case of D factor--up to normal. CONCLUSION: The data obtained in the study indicates the presence of complement alternative pathway activation in atopic dermatitis in children and the possibility of use of factor B and D functional activity analysis for diagnostic and prognostic purposes.

[Comparative analysis of informative-diagnostic properties of mucosa immune-reactivity parameters].

AIM: Study the features of immune-reactivity expression in mucosa depending on their topicity and etiopathogenesis of the pathological process. MATERIALS AND METHODS: Data from 30 clinically healthy children and 77 children with acute and recurrent diseases of respiratory tract: 51--with acute and 15--with chronic bronchitis; as well as 132 women: 41--with active stage of acute urogenital chlamydia infection, 29--with recurrent chronic process, 30--with non-recurrent form and 32 clinically healthy women were analyzed. Saline and urogenital tract mucosa discharge was analyzed for IgG, sIgA and secretory component, IL-1beta, 4, 6, 8, 9, 10, 12, IFNgamma, TNFalpha and GM-CSF, TLR-2, TLR-3, TLR-4, TLR-8 gene expression levels as well as content of lysozyme, total protein and leucocytes. RESULTS: Solidity, universality and practically single-stage triggering of mucosa immune reaction mechanisms to intervention by foreign agents regardless of their localization was confirmed. A dependence of immune-reactivity expression on the form of pathologic process, its localization and qualitative and quantitative characteristics of the infectious agents was clearly seen. The highest level of clinical-laboratory and immunological parameters is inherent for patients with acute processes in urogenital tract (cervical canal and urethra), especially cause by mixed infections. CONCLUSION: Immune diagnostic parameters of mucosa among which TLR system is especially notable have high information properties allowing not only diagnostics of inflammatory process but also differentiating its form and character our course.

[Sensitivity of corynebacterium diphtheriae strains to antibacterial preparations].

AIM: Study the prevalence and mechanisms of resistance in circulating C. diphtheriae strains. MATERIALS AND METHODS: 664 C. diphtheriae strains isolated in 1987 - 2013 in various regions of Russia and sent to the reference center of Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology were the object of the study. Antibiotic sensitivity of the strains was studied by disk-diffusion and E-test methods using 10 antimicrobial preparations. Nucleotide sequence analysis was carried out by using BLAST program and EMBL/GenBank database. RESULTS: Most of the studied strains turned out to be sensitive to all the antibacterial preparations used. 1.2% of C. diphtheriae strains turned out to be resistant to penicillin and 6.0% had intermediate level of resistance. 0.4 - 0.6% of the strains had intermediate level of resistance to macrolides, and 4.0 - 4.4% were resistant. 2.0% of the strains had multiple resistance. Erm(X)-specific PCR carried out in this study showed that all the C. diphtheriae strains resistant to macrolide antibiotics carry erm(X) gene. CONCLUSION: The results of the study indicate a fairly high level of prevalence for C. diphtheriae strains resistant to antibiotics.

[Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.