Function Of Immunocompetent Cells Research Articles

PD-1 AND Tim-3 Expression on different subpopulations of monocytes in chronic often recurrent herpesvirus infection

More than half of the world’s population is infected with the herpes simplex virus. In most cases, infection is not accompanied by symptoms, but in some people the disease occurs as a chronic infection with frequent and severe relapses. One of the most likely reasons for this may be a dysregulation of the immune system. In recent years, the role of checkpoint molecules, in particular PD-1 and Tim-3, in the regulation of the immune response and the functions of immunocompetent cells has been actively studied. Activation of PD-1 and Tim-3 on T cells has previously been shown to suppress the immune response. PD-1 and Tim-3 are also expressed on other immune cells, in particular monocytes. However, the expression of these molecules on monocytes during chronic viral infections has not been previously studied. The study was aimed at assessing the level of PD-1 and Tim-3 expression on various populations of monocytes in patients with chronic often recurrent herpesvirus infection. Twenty-six patients were recruited into the study. All patients received antiviral and immunomodulatory therapy in the immunological department. The number of classical, intermediate, and non-classical monocytes and the expression of PD-1 and Tim-3 on monocytes, were assessed by flow cytometry before and after the therapy. Monocytes were isolated from peripheral blood, and subpopulations were divided according to the level of expression of CD14 and CD16. In patients with herpes, a reduced number of monocytes was observed in comparison with healthy donors. The relative number of PD-1-positive monocytes, the mean fluorescence intensity of PD-1 and Tim-3, and the number of double-positive cells were reduced in herpes patients in all three monocyte subpopulations examined. Three months after therapy, the response to the therapy was assessed; patients who did not have a single recurrence of herpes within 3 months were considered to respond. Responding patients had a lower initial content of double-positive cells among intermediate and non-classical monocytes. The decrease in the level of PD-1 and Tim-3 positive monocytes during herpesvirus infection revealed in the present study may indicate the involvement of monocytes deficient in the expression of checkpoint molecules in the pathogenesis of the disease.

Minerals and their role in the optimal functioning of the immune system – literature review

An adequate supply of minerals in the diet is crucial for the proper functioning of the immune system. This applies to both the mechanisms of innate and adaptive immunity, and in particular, the pro- and anti-inflammatory balance of the body. For most people, a balanced diet is sufficient to provide the body with adequate amounts of minerals. However, certain groups are particularly at risk of deficiencies in these nutrients. These include people who perform frequent and intense sports training when the body does not have an opportunity to regenerate properly. The aim of this paper was to discuss the role of minerals in the suitable functioning of the immune system. The following review of the latest literature focuses on the role of magnesium, zinc, iron and selenium as the components of greatest importance in immunology. The effects of a deficiency of these minerals and their impact on the maturation and function of immunocompetent cells, antibody production, cytokine production and immune pathways are discussed. The review was based on the available data collected in the PubMed database and in the Google Scholar search engine using the keywords: “the role of magnesium in the immune system”, “the role of zinc in the immune system”, “the role of iron in the immune system”, the role of selenium in the immune system”, “mineral deficiencies in athletes”, “impact of intense physical exercise on the immune system”.

Immune system rejuvenation—approaches and real achievements

Interest in the mechanisms of aging of the immune system has not faded over the past 100 years, and it is caused by the immune-mediated development of age-related pathology, including autoimmune organ damage, reduced vaccination efficiency, atherosclerosis, the development of cardiovascular pathology, etc. In contrast to many other organs and systems, the immune system aging begins at an early age and has more pronounced changes that lead to the development of secondary pathology, which significantly affects life expectancy. But an effective strategy to restore immune function has not been developed yet. During this time, the mechanisms of age-related dysfunction of organs and cells of both the adaptive and innate immune systems were studied in detail—thymus involution, a decrease in the potential of hematopoietic stem cells, impaired differentiation and functions of immunocompetent cells, as well as the ways of their interaction. Numerous potential therapeutic targets have been identified and various approaches have been used to implement such therapeutic interventions. The review is devoted to replacement therapy using transplantation of hematopoietic stem cells (HSCs) and young lymphoid cells and tissues, cellular and systemic factor exchange in heterochronic parabiosis, and some other widely used life extension approaches. It has been proven that cell therapy using young cells to rejuvenate the old immune system, unfortunately, often turns out to be ineffective because it does not eliminate the root cause of age-related changes. The phenomenon of inflamm-aging that develops with age can significantly affect both the aging of the organism in general and the functioning of immunocompetent cells in particular. Therefore, the most promising direction in the restoration of immune functions during aging is systemic approaches that have a complex effect on the organism as a whole and can slow down the aging process.

Features of the cytokine profile under its modification with technogenic factors in conditions of experiment in vitro (on the example of benz(a)pyrene and SARS-CoV-2 vaccine antigen)

Introduction. The immune system plays the key role in the formation of adaptive responses and is the most sensitive to environmental exposures. An immune response under exposure to viruses or other factors is induced by toll-like receptors stimulating production of pro-inflammatory cytokines. Simultaneous exposure to exogenous chemical pollutants in ambient air modifies the adaptation process.
 Materials and methods. An in vitro experiment was accomplished on samples of peripheral blood. The study focused on a mixed population of immune-competent cells (n=64 samples). Effects produced by exogenous factors (benz(a)pyrene, SARS-CoV-2) and managing elements (interleukin-1β, cortisol) were considered influencing factors. All the lymphocyte cultures were incubated for 72 hours; after that, the quantitative content of cytokines in the samples was determined by the ELISA tests.
 Results. The inhibition of cytokines was experimentally demonstrated when the SARS-CoV-2 vaccine antigen was introduced into cell culture in combination with cortisol and an immunomodulator (IL-6, IL-10), and a significant decrease in the level of INF-gamma in samples with the addition of IL-1β was also noted. Benz(a)pyrene exerted a catalytic effect on the cytokine-producing function of immunocompetent cells with an increase in the production of IL-6 and IFN-gamma relative to spontaneous production. Suppression of cytokines (IL-6, IFN-gamma, and IL-10) was observed in samples containing vaccine antigens SARS-CoV-2, compared with the spontaneous level, which suggests the formation of possible mechanisms of post-vaccination complications.
 Limitations. The study has no limitations associated with the use of the selected methods or characteristics of the research objects.
 Conclusions. Experimental modelling in vitro made it possible to estimate the additive effects of the mixed action of benz(a)pyrene and SARS-CoV-2 (vaccine antigen) on protein molecules and hyperproduction of inflammatory modulators was evaluated. The study aimed to facilitate investigation of the examined mechanism and development of relevant programs for preventing risks of negative effects produced on health by chemical and biological factors.

Clinical and pathogenetic significance of immunity factors in congenital generalized infection caused by the herpes simplex virus

Intrauterine infections are serious diseases that largely determine the level of infant mortality. Newborns who have had intrauterine infections often have long-term consequences, leading to disability. One of the intrauterine infections is a congenital infection caused by the herpes simplex virus (neonatal herpes). Neonatal herpes occurs less frequently (1:2000 live births) than cytomegalovirus fection, but the clinical symptoms in this disease are characterized by multiorgan damage.Purpose. To determine the role of immune factors in the development of congenital generalized HSV infection.Material and methods. Twenty-two newborns with a severe form of congenital generalized infection caused by the herpes simplex virus infection were examined (group I). The control group consisted of 26 healthy newborns born to women with uncomplicated pregnancy and childbirth. Determination of the population and subpopulation composition of peripheral blood lymphocytes and monocytes, the level of expression of activation markers, T-regulatory cells (Treg) was carried out by laser fl w cytometry using reagents from Immunotex (France), Caltag (USA), HyCultbiotechnology (Netherlands): FITC (fl escein isothiocyanate) — labeled CD3+, CD4+, CD8+, CD 16+, CD19+, CD282+ and PE (phycoerythrin)-labeled CD95+, CD25+, CD14+. Determination of the number of lymphocytes that have entered apoptosis using a diagnostic kit including Annexin-V, labeled with FITC and propidium iodide (PI), (Caltag, USA). The concentration of IFN-γ, IFN-α, IL-12 in the blood serum of newborns was determined by ELISA using BenderMedsistems test systems.Results. The development of a congenital generalized infection caused by the herpes simplex virus is associated with a lack of IFN-α, IFN-γ, IL-12 production, a decrease in the number of monocytes expressing TLR-2, a decrease in the relative number of CD8+, CD16+ lymphocytes, CD25+ activation markers, on the surface of NK cells, in combination with an increase in CD16 + CD95 +, AnnexinV + PI +, the number of Tregs.Conclusion. The results of the work indicate suppression of the early stages of the innate immune response, impaired effector function of immunocompetent cells, apoptosis processes

Concentration of anti-inflammatory cytokines in supernatants of peripheral blood cell cultures in children with autoimmune and infectious diseases

Cytokines belong to the class of signaling molecules, being involved into regulation of proliferation, differentiation and effector functions of immunocompetent cells. The ratio of pro- and anti-inflammatory cytokines is important for development of any inflammatory process. IL-1ra, IL-4, IL-10 are among the most important anti-inflammatory cytokines. Their function is to limit and suppress immune response in inflammatory processes of any etiology. In this respect, the aim of this study was to evaluate production of the anti-inflammatory cytokines IL-1ra, IL-4 and IL-10 by peripheral blood cells in children with autoimmune and infectious diseases. Patients and methods: Pediatric parients (2-17 years old) participated in the study including those with juvenile idiopathic arthritis (n = 101); unspecified reactive arthropathy (n = 24); systemic lupus erythematosus (SLE, n = 14); chronic viral hepatitis C (n = 24). 33 healthy children (n = 33) comprised the control group. Heparinized blood samples were diluted with glutamine-containing medium RPMI-1640. Control samples were not treated by any stimulants, and the stimulated samples were supplied with phytohemagglutinin (20 mkg/ml). The samples of diluted blood were incubated for 24 hours (37 C, 5% CO2). The supernates were frozen once. The concentrations of IL-1ra, IL-4 and IL-10 in these cell supernatants were determined by ELISA technique (Vector-Best, Russia). Results: It was found that the spontaneous production of anti-inflammatory cytokines (IL-1ra, IL-4 and IL-10) didnt differ, or was lower in the groups of patients with SLE, juvenile idiopathic arthritis and hepatitis C if compared with control group. SLE is an autoimmune disease, whereas juvenile arthritis is of mixed autoimmune-autoinflammatory etiology. Chronic hepatitis C is a viral disease, but autoimmune responses may manifest at the chronic stage of the disorder. Decreased production of anti-inflammatory cytokines could be an evidence for autoimmune mechanisms of these diseases, despite their different etiology. More intensive spontaneous production of IL-1ra and IL-10 in children with unspecified reactive arthropathy may suggest some compensatory reactions which inhibit development of inflammation in this disorder. IL-1ra, IL-4 and IL-10 production in stimulated cultures didnt differ between all groups of the patients, or it was lower in comparison with healthy children. Decrease cytokine production in groups of children with different diseases suggests exhausted functional reserve of immunocompetent cells caused by their chronic activation.

Hematopoiesis, Inflammation and Aging-The Biological Background and Clinical Impact of Anemia and Increased C-Reactive Protein Levels on Elderly Individuals.

Anemia and systemic signs of inflammation are common in elderly individuals and are associated with decreased survival. The common biological context for these two states is then the hallmarks of aging, i.e., genomic instability, telomere shortening, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. Such aging-associated alterations of hematopoietic stem cells are probably caused by complex mechanisms and depend on both the aging of hematopoietic (stem) cells and on the supporting stromal cells. The function of inflammatory or immunocompetent cells is also altered by aging. The intracellular signaling initiated by soluble proinflammatory mediators (e.g., IL1, IL6 and TNFα) is altered during aging and contributes to the development of both the inhibition of erythropoiesis with anemia as well as to the development of the acute-phase reaction as a systemic sign of inflammation with increased CRP levels. Both anemia and increased CRP levels are associated with decreased overall survival and increased cardiovascular mortality. The handling of elderly patients with inflammation and/or anemia should in our opinion be individualized; all of them should have a limited evaluation with regard to the cause of the abnormalities, but the extent of additional and especially invasive diagnostic evaluation should be based on an overall clinical evaluation and the possible therapeutic consequences.

EFFECT OF IMUNOFAN INFLUENCE ON THE STRUCTURE OF THE TESTES, HORMONAL AND CYTOKINE PROFILE OF IMMATURE EXPERIMENTAL ANIMALS

The aim: It was the establishing the features of changes in the structure of the testes of experimental animals, as well as immunological, hormonal and cytokine parameters of blood plasma during stimulation. Materials and methods: The study was carried out on 60 white male immature rats. Imunofan was used at a dosage of 50 μg. The organs were weighed, the relative mass was calculated, and the linear dimensions were determined. The morphometriv parameters of the epitheliospermatogenic layer were measured. The number of supporting cells and interstitial endocrinocytes was counted, as well as the volume of cell nuclei. The level of reproductive hormones in the plasma and the concentration of cytokines were determined. Results: The results obtained indicate the development of readaptation processes in the testes after the use of the Imunofan against the background of environmental immunosuppression. The ability of the drug to stimulate the production of cytokines and hormones normalizes the function of immunocompetent cells, which is manifested in the stabilization of the immune homeostasis of the testes. Conclusions: In response to the immunostimulating effect of Imunofan, a pronounced reaction is observed on the part of the testes of immature animals, which is due to the sensitivity of morphogenetic processes in the organ to external influences and the formation of mechanisms of their regulation, characteristic of this period of ontogenesis.

IMMUNOCOMPETENT CELLS OF THE EPITHELIAL LAYER OF SKIN, CONJUNCTIVA AND ORAL CAVITY IN CONDITIONS OF DAMAGE, TRAUMA AND INJURY

Nowadays, the data on the topography, composition and functions of immunocompetent cells in the epidermis, as well as in the covering stratified epithelial lining of the conjunctiva and oral cavity have not been systematized. The interaction of these cells in the stratified (covering) epithelium during damage, trauma and injury remain poorly understood at immunohistochemical and electron microscopic manifestations. To clarify the role of the noted cells in the pathogenesis and sanogenesis in damage and injuries of skin, mucosal layer of conjunctiva and oral cavity it is advisable to study comprehensively corresponding samples of these epithelia in humans and in experiments on small laboratory animals with an emphasis on the expression of MIF and its receptor CD74.

Disturbance of serotonergic regulation of hematopoietic stem cells (HSCS CD 34+) and blood mononuclear cells (BMCS) in patients with multiple sclerosis (MS)

Background and goals. Serotonin is involved in the mechanisms of regulation of the function of immunocompetent cells through the receptor apparatus. The aim of the study was to evaluate the expression capacity (EC) of BMCs and HSCs under the influence of serotonin - creatine sulfate at a dose of 10−4 M in the “in vitro”test system(TS). Violation of the receptor apparatus of cells serotonin led to a change in their quantitative registration.

Immune properties of lactoferrin and its protective role in new coronavirus infection COVID-19

Thousands of studies have been conducted to study the new SARS-CoV-2 coronavirus, its infectious properties, transmission routes and all associated with the clinical manifestations and severity of COVID-19, especially with potential treatments. Lactoferrin is a member of the transferrin family, which is synthesized by epithelial cells of mammalian internal glands and is widely present in various secretory fluids such as milk, saliva, tears, and nasal secretions. Lactoferrin is one of the components of the innate humoral immunity, regulates the functions of immunocompetent cells and is a acute phase protein. Lactoferrin has strong antioxidant and anti-inflammatory properties. This review assesses the possibility of using lactoferrin as a supplement in immunocorrective therapy programs for viral diseases, including the novel coronavirus infection COVID-19.

COMPARATIVE CHARACTERISTICS OF CHANGES IN HEMO - AND LYMPHOMICROCIRCULATORY VESSELS OF ILEUM ACCUMULATED LYMPHOID NODES OF RATS IN THE CASE OF APPLICATION OF INFUSION SOLUTIONS IN EXPERIMENTAL BURN DISEASE

Relevance. Thermal burns of the skin cause the development of burns, the main factor of which is endogenous intoxication. The infusion of detoxification solutions is a mandatory component of the treatment of burns, as it corrects its course and prevents the development of certain stages and complications. According to the stage of the burn disease and the different direction of its links in its pathogenesis, infusion therapy should not only restore water-electrolyte balance and detoxify the body, but also contribute to the normalization and stabilization of vital (including immune) body functions.
 Objective: study of changes in the vessels of the hemo- and lymphomicrocirculatory system of Peyer's patches in burnt rats at the stages of burn disease, under conditions of intravenous infusion of isotonic sodium chloride solution and combined colloidal-hyperosmolar solutions (lactoprotein and sorbitolum).
 Materials and methods. The experiment was performed on 72 white rats. Experimental animals were divided into 4 groups (18 animals in each group). I, II, III - rats with skin burn trauma, which received a separate infusion of isotonic sodium chloride (I), lactoprotein with sorbitol (II) and hecoton (III), at a dose of 10 ml / kg. IV - intact animals (control group).
 Simulation of burn disease was performed by inflicting burn injury by applying to the lateral surfaces of the body of animals four copper plates, which were previously kept for 6 minutes in water with a constant temperature of 100 ° C. Histological and electron microscopic examination were performed. Light microscopy was used.
 Results. Intravenous administration of the applied infusion solutions caused various phase changes of the hemo- and lymphomicrocirculatory tract of Peyer's patches of the ileum of burnt rats, depending on the applied solution. In the case of infusion of burnt rats with 0.9% sodium chloride solution, the negative effects of burn disease were exacerbated, which were manifested by damage to the vascular wall of the hemo- and lymphocapillary channels, resulting in plasma and lymph seepage through the affected areas into the perivascular space. This process was accompanied by a violation of the rheological properties of blood, the formation of edema. The established "membrane-plastic effect" of lactoprotein with sorbitol revealed clear organ-specific features, which had manifestations of penetration through the damaged wall of microvascular electron-dense impregnations, which contributed to a significant thickening of the basement membrane in the wall of the blood capillary formation and its gradual formation of rounded membranous structure. This structure of variable electron density not only strengthened the vascular wall, but also served as a closure, helping to close the vascular lumen at the site of largest damage. The difference between the perinodal lymphatic capillaries in burnt rats infused with lactoprotein and sorbitol is characterized by the phenomenon of "overflow" of the lymphocapillary channel with cells in different functional states. In the case of infusion of hecoton solution, the effect of "overflow" of the lymphocapillary channel was not observed, which indicates adequate implementation of the immune function of immunocompetent cells.
 Conclusions. Intravenous infusion of colloid-hyperosmolar solutions causes various changes in the hemo- and lymphomicrocirculatory tract of Peyer's patches. Infusion of a 0.9% sodium chloride solution leads to a deepening of the negative consequences of burn disease, which manifests itself in the form of damage to the vascular wall of the hemo- and lymphocapillary channels. Infusion of solutions of lactoprotein with sorbitol and hecoton helps to preserve the vascular wall of the nodular lymphatic capillaries. When a solution of lactoprotein with sorbitol is applied around the damaged vessels of blood capillaries and venules, annular membrane formations are formed, which promote selective recirculation of structurally intact lymphocytes.

ДЕФИЦИТ LRBA: ОБЗОР ЛИТЕРАТУРЫ И ОПИСАНИЕ КЛИНИЧЕСКИХ НАБЛЮДЕНИЙ

Since the description of the first primary immunodeficiencies (PIDs) in the 50–60s of the last century, they have been the subject of intensive research aimed at elucidating their etiology and finding effective treatments. The development of next-generation sequencing (NGS) methods made it possible to reveal the genetic basis of many new forms of PID, which were previously attributed to various syndromes due to their clinical and immunological characteristics. An example of such a PID is the LRBA (the lipopolysaccharide-responsive and beige-like anchor protein) deficiency, sometimes called LATAIE [LRBA deficiency with autoantibodies, regulatory T (Treg) cell defects, autoimmune infiltration, and enteropathy]. The article provides information on the main role of the LRBA molecule in the functions of immunocompetent cells, describes immunological disorders and clinical manifestations of LRBA deficiency and the principles of treatment of diseases. Two own observations of LRBA deficiency are presented.

Relapsing-remitting multiple sclerosis: clinical and immunological aspects of the pathology on the example of molecules Sema4D and CD72

To study the expression of Sema4D (CD100), receptor CD72 and a role of Sema4D-CD72-dependent signal in the control of the functions of immunocompetent cells in relapsing-remitting multiple sclerosis (RRMS). We studied 76 patients, including 52 with RRMS (41 in remission and 11 in exacerbation), 35 women (67.3%) and 17 men (32.7%) aged 18-55 years, who did not receive disease-modifying drugs, and 24 healthy donors. A controlled clinical and immunological examination of patients with RRMS was carried out proving the involvement of the Sema4D molecule and its CD72 receptor in pathological reactions in this autoimmune disease. The use of SemaD as a target in the treatment of RRMS is scientifically substantiated. In case of a positive decision on the use of anti-Sema4D drugs, it will be necessary to take into account the effects of semaphorin not only in the central nervous system, but also in the immune system of patients with RRMS.

Modern Conceptions about the Mechanisms of Interaction Between Biofilm and Cellular Immunity Factors

Features of the cellular immune response in the presence of a microbial biofilm are well described in the literature. Based on numerous studies, it became possible to establish a number of patterns: mature biofilms are better protected from immune factors, the effectiveness of antibiofilm strategies depends on species of the microorganisms, forming the biofilm, and, accordingly, on the composition of the biopolymer matrix. For example, rhamnolipids and alginate of Pseudomonas aeruginosa exert a significant negative effect on the function of immunocompetent cells. The bacteria of biofilms became able to turn to their advantage many of the protective reactions developed by the immune system and fixed evolutionarily, applying them for the growth and development of the microbial consortium.

Modern Conceptions about the Mechanisms of Interaction Between Biofilm and Cellular Immunity Factors

Features of the cellular immune response in the presence of a microbial biofilm are well described in the literature. Based on numerous studies, it became possible to establish a number of patterns: mature biofilms are better protected from immune factors, the effectiveness of antibiofilm strategies depends on species of the microorganisms, forming the biofilm, and, accordingly, on the composition of the biopolymer matrix. For example, rhamnolipids and alginate of Pseudomonas aeruginosa exert a significant negative effect on the function of immunocompetent cells. The bacteria of biofilms became able to turn to their advantage many of the protective reactions developed by the immune system and fixed evolutionarily, applying them for the growth and development of the microbial consortium.

Immunomodulatory effects of some Namibian plants traditionally used for treating inflammatory diseases

Ethnopharmacological relevanceAcanthosicyos naudininus, Gomphocarpus fruticosus, and Cryptolepis decidua are, according to the knowledge of traditional healers, used in Namibia to treat inflammatory disorders such as pain, fever and skin rashes.Aim of the study: The present study was conducted to evaluate the immunomodulatory effects and the possible underlying mechanisms of action of the plant extracts on peripheral blood mononuclear cells (PBMCs) such as T-lymphocytes. Materials and methodsMethanolic and EtOAc extracts of A. naudinianus, G. fruticosus and C. decidua were analysed for their immunomodulatory potential. PBMCs were isolated from the blood of healthy donors and incubated with the plant extracts at concentrations 100, 30, 10, 3, 1 and 0.3 μg/mL. Effects on proliferation and viability of activated human lymphocytes were assessed in comparison to ciclosporin A by flow cytometry using carboxyfluorescein succinimidyl ester (CFSE) and WST-1 assay. Flow cytometry by annexin V/propidium iodide (PI) staining was performed to investigate the necrotic/apoptotic effect of the plant extracts on mitogen-activated human lymphocytes. In addition, analysis of the influence of plant extracts on the regulatory mechanisms of T-lymphocytes was performed using activation marker and cytokine production assays. An HPLC-PDA-ELSD-ESIMS profile was recorded for each of the extracts. ResultsT-lymphocyte proliferation was inhibited in a dose-dependent manner by the extracts of A. naudinianus, G. fruticosus, and C. decidua in concentrations not causing apoptosis or necrosis. This effect was mediated by inhibition of lymphocyte activation, specifically the suppression of CD25 and CD69 surface receptor expression. Moreover, the extracts suppressed effector functions, as indicated by reduced production of IFN-γ and IL-2. Based on the HPLC profile, possible responsible compound classes could be identified for the extracts of A. naudinianus (cucurbitacins) and C. decidua (indole alkaloids), but not for G. fruticosus. ConclusionsThe data show that the extracts of A. naudinianus, G. fruticosus and C. decidua have in vitro immunomodulatory activity and they interfere with the function of immunocompetent cells, suggesting an anti-inflammatory mode-of-action. The present chemical determination and pattern recognition results explain the therapeutic potency. However, further studies to investigate the therapeutic potential of the plants in inflammatory disorders should be done.

Combined effect of silver nanoparticles and aluminium chloride, butylparaben or diethylphthalate on the malignancy of MDA-MB-231 breast cancer cells and tumor-specific immune responses of human macrophages and monocyte-derived dendritic cells

The aim of this study was to assess whether silver nanoparticles (AgNP) or selected cosmetic ingredients may modify functions of various immunocompetent cell populations. To this end, the effect of two AgNP (size of 15 nm or 45 nm), alone and in combination with aluminium chloride, butyl paraben, di-n-butyl phthalate or diethyl phthalate was assessed on: (1) migration and invasion of MDA-MB-231 human breast cancer cells; (2) M1/M2 polarization of phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages (M0) and (3) activation/maturation of monocyte-derived dendritic cells (DCs). The results of this study showed that neither any of the test chemicals alone nor the mixtures significantly changed the migration or invasion ability of MDA-MB-231 cells following, both 72-h and 21-day exposure. Analysis of the expression of marker genes for both M1 (IL-1B, CXCL9, TNF) and M2 (DCSIGN, MRC1) polarization revealed that the chemicals/mixtures did not activate M1/M2 differentiation of the M0 macrophages. In addition, no significant changes were observed in the expression of CD86, HLA-DR and CD54 surface markers and phagocytic activity of DCs following 48-h exposure to AgNP alone or in combination with test compounds.Our study suggests that AgNP alone or in combination with tested cosmetic ingredients do not alter function of immunocompetent cells studied.

Ishrana kritično obolelih pacijenata - uloga glutamina u imunomodulaciji ishranom

Glutamine is a nonessential amino acid, conditionally essential in stressful conditions (catabolism/hyper catabolism). The lungs, liver, brain, and skeletal muscles take part in specific glutamine synthesis pathways. Plasma concentration of this amino acid is about 50% of total amino acid concentration and about 60% of free amino acids in the body. It is a significant source of energy for all cells, including immune cells. Glutamine can be used as a substrate for nucleotide synthesis. In the last few decades, advanced technology significantly changed the treatment of critically ill patients. Mechanical ventilation, blood products transfusion, renal replacement therapy, invasive monitoring, and many other technical procedures prolong the life of patients by changing and modulating homeostasis and developing new pathways and mechanisms of adaptation - allostasis. Systemic inflammatory response and immunomodulatory activity are part of complex underlying mechanisms involved in allostasis. Nutrition is an important part of the strategy for the treatment of critically ill patients. Based on recently published results, few nutrients (omega-3 fatty acids, arginine, glutamine), when added to the standard formula for enteral and parenteral nutrition, reduce intensive care unit (ICU) stay, infection rate, and the duration of mechanical ventilation in critically ill patients. Glutamine has a high immunomodulatory capacity, as fuel for muscles and a "shuttle" for nitrogen, protecting lung and gut function as well as the function of immunocompetent cells. The most vulnerable systems in COVID-19 patients are respiratory and renal. Despite no universally accepted strategy, treatment with glutamine could have an important role in protecting the cellular integrity of immune cells, alveolar-capillary, and enteral membrane.

Immune paradigm and immunosuppressive dominance in the pathogenesis of major diseases of the modern man

The article discusses the determining role of immunopathogenesis of the main diseases of the modern man (cancer, atherosclerosis, autoimmune, allergic and infectious diseases). In this regard, the concept of «immune paradigm» is introduced. There is evidence that any pathology is based on the classical immune response to the antigen, whether auto- or xenoantigen, with all stages of its development and parallel changes in the state of immune tolerance: its breakdown in cases of autoimmune and allergic diseases and atherosclerosis; its establishment in cases of cancer and infectious diseases. In the meantime, it is emphasized that the immunopathogenesis is based on insufficient or increased function of immunocompetent regulatory cells with suppressive activity. Here the concept of «immunosuppressive dominant» is introduced. Finally, we discuss the need for fundamental changes in treatment of these diseases, with a focus on molecular and cellular immunotherapy methods and development of integrated approaches to their application.