RESUMEN
The article substantiates possibility of application of point enzyme-linked immunosorbent assay (dot-technique) for detecting viral antigens in samples from patients. To diagnose adenovirus infection conjugate of virus-specific monoclonal antibodies and peroxidase of horse-radish were used The chromatographic rectification of conjugate from free peroxidase permits diminishing background coloring of nitrocellulose membrane and therefore to increase sensitivity. The application of direct conjugates on the basis of virus-specific monoclonal antibodies increases specifcity of dot-technique and significantly shortens time period of analysis. As in case of application of direct conjugates on the basis of polyclonal serum, samples from patients require preliminary processing with detergent for preventing non-specific reactions. The dot-technique demonstrates good coincidence with data of polymerase chain reaction and after clinical trials it can be used in diagnostic of human viral infections.
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Infecciones por Adenoviridae/diagnóstico , Adenoviridae/aislamiento & purificación , Anticuerpos Monoclonales/química , Anticuerpos Antivirales/química , Antígenos Virales/sangre , Immunoblotting/métodos , Adenoviridae/química , Adenoviridae/inmunología , Infecciones por Adenoviridae/inmunología , Infecciones por Adenoviridae/virología , Especificidad de Anticuerpos , Pruebas de Inhibición de Hemaglutinación , Peroxidasa de Rábano Silvestre/química , Humanos , Inmunoconjugados/química , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Studies comparing the efficacy of dawn simulation to conventional bright light for the treatment of seasonal affective disorder (in parallel groups) have yielded conflicting results. This crossover study investigated treatment outcomes and long-term treatment preference. METHODS: Forty winter depressives were treated for a week with bright light (4.300lx for 30-45min shortly after awakening) or dawn simulation (gradually increasing light during the last 30min of sleep achieving 100lx before alarm beep, with the dawn simulator placed closer to the open eyes for a further 15min: 250lx). The depression level was self-rated using SIGH-SAD-SR. RESULTS: Depression scores reduced similarly following bright light and dawn simulation: for 43.8% and 42.2% (medians), respectively; efficacy ratio was 23:17. The preference was also similar (21:19). Among those who preferred bright light, the most common reason was that they perceived the bright light to be more effective (19/21; it was more effective, p=0.0096; this subgroup tended to have more severe depression) and ease of use (6/21). Among those who preferred the dawn simulator, the reasons were a more "natural" action (9/19), device compactness and/or time-saving (10/19) and in 4 cases where bright light caused eyestrain. LIMITATIONS: Not overhead naturalistic light for dawn simulation, self-rating of depression. CONCLUSIONS: Dawn simulation is similarly effective to bright light in the treatment of winter depression. Patients with more severe depression tended to report greater improvement with bright light; in such cases, this would outweigh the non-clinical advantages of dawn simulation.
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Prioridad del Paciente , Fototerapia/métodos , Trastorno Afectivo Estacional/terapia , Adulto , Anciano , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Afectivo Estacional/psicología , Resultado del Tratamiento , Adulto JovenRESUMEN
Recently, due to spread of dangerous and especially dangerous infections much attention is given to development of complex approaches to their prophylaxis and therapy. Data on use of immune modulators, cytokines, probiotics, preparations of plant origin for non-specific prophylaxis of especially dangerous infections are analyzed in the review, and expediency of their combined use with specific and emergency prophlaxis of these diseases is evaluated.
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Infecciones Bacterianas/inmunología , Infecciones Bacterianas/prevención & control , Citocinas/inmunología , Factores Inmunológicos/uso terapéutico , Bacterias/efectos de los fármacos , Bacterias/inmunología , Bacterias/patogenicidad , Infecciones Bacterianas/microbiología , Citocinas/uso terapéutico , Humanos , Factores Inmunológicos/inmunología , Fitoquímicos/inmunología , Fitoquímicos/uso terapéutico , Probióticos/uso terapéuticoRESUMEN
AIM: Study the mechanisms of formation of cell and humoral immunity against pertussis, diphtheria and tetanus in children immunized with immunobiological preparations (APDT vaccine and ADT anatoxin). MATERIALS AND METHODS: 30 practically healthy children (6 - 9 years of age) immunized with APDT and ADT-M preparations had TLR2, TLR4 expression determined in mononuclear cells (MNC). Vaccine preparations (APDT, ADT-M, AD-M, AT) and Corynebacterium diphtheriae gravis tox+, C. diphtheriae mitis tox- and Bordetella pertussis 345 were used as ligands. Cytokine production was determined in EIA. Content of anti-diphtheria, anti-tetanus and anti-pertussis antibodies--by PHA reaction and EIA. RESULTS: During stimulation with vaccines and B. pertussis 345 strain MNC were characterized by an increase (p < 0.05) of expression level of TLR2 and TLR4 and did not respond to stimulation with C. diphtheriae gravis tox+ and C. diphtheriae mitis tox- strains. Similar results were obtained during study of cytokine production (TNFalpha, IL-1, IL-6). A direct correlation between levels of antitoxic antibodies against diphtheria and tetanus (R = 0.486), antibacterial antibodies against pertussis and diphtheria was detected (R = 0.529). CONCLUSION: Analysis of cytokine production profile and determination of surface TLR expression can be used during evaluation of functional status of innate immunity cells and intensity of post-vaccinal immunity.
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Anticuerpos Antibacterianos/biosíntesis , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Difteria/prevención & control , Tétanos/prevención & control , Toxoides/inmunología , Tos Ferina/prevención & control , Anticuerpos Antibacterianos/inmunología , Bordetella pertussis/química , Bordetella pertussis/inmunología , Niño , Corynebacterium diphtheriae/química , Corynebacterium diphtheriae/inmunología , Difteria/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Femenino , Expresión Génica , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Inmunización , Interleucina-1/biosíntesis , Interleucina-1/inmunología , Interleucina-6/biosíntesis , Interleucina-6/inmunología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/microbiología , Masculino , Tétanos/inmunología , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/inmunología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/inmunología , Toxoides/administración & dosificación , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/inmunología , Tos Ferina/inmunologíaRESUMEN
Metastatic breast cancer cannot be treated successfully. Currently, the targeted therapies for metastatic disease are limited to human epidermal growth factor receptor 2 and hormone receptor antagonists. Understanding the mechanisms of breast cancer growth and metastasis is therefore crucial for the development of new intervention strategies. Here, we show that FER kinase (FER) controls migration and metastasis of invasive human breast cancer cell lines by regulating α6- and ß1-integrin-dependent adhesion. Conversely, the overexpression of FER in non-metastatic breast cancer cells induces pro-invasive features. FER drives anoikis resistance, regulates tumour growth and is necessary for metastasis in a mouse model of human breast cancer. In human invasive breast cancer, high FER expression is an independent prognostic factor that correlates with high-grade basal/triple-negative tumours and worse overall survival, especially in lymph node-negative patients. These findings establish FER as a promising target for the prevention and inhibition of metastatic breast cancer.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Integrina alfa6/metabolismo , Integrina beta1/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Actinas/metabolismo , Animales , Anoicis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Adhesión Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Matriz Extracelular/metabolismo , Femenino , Humanos , Ratones , Ratones Noqueados , Metástasis de la Neoplasia , Proteínas Tirosina Quinasas/genética , Interferencia de ARN , Carga TumoralRESUMEN
Cancer treatments are increasingly focusing on the molecular mechanisms underlying the oncogenic processes present in tumors of individual patients. Fibroblast growth factor receptors (FGFRs) are among the many molecules that are involved in oncogenesis and are currently under investigation for their potential as drug targets in breast cancer patients. These receptor tyrosine kinases play a role in several processes including proliferation, angiogenesis, and migration. Alterations in these basal processes can contribute to the development and progression of tumors. Among breast cancer patients, several subgroups have been shown to harbor genetic aberrations in FGFRs, including amplifications of FGFR1, FGFR2, and FGFR4 and mutations in FGFR2 and FGFR4. Here, we review in vitro and in vivo models that have partly elucidated the molecular implications of these different genetic aberrations, the resulting tumor characteristics, and the potential of FGFRs as therapeutic targets for breast cancer treatment.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Descubrimiento de Drogas , Terapia Molecular Dirigida , Receptores de Factores de Crecimiento de Fibroblastos/fisiología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/fisiología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Carcinoma/diagnóstico , Carcinoma/genética , Descubrimiento de Drogas/métodos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Modelos Biológicos , Terapia Molecular Dirigida/métodos , Receptores de Factores de Crecimiento de Fibroblastos/genética , Receptores de Factores de Crecimiento de Fibroblastos/metabolismoRESUMEN
AIM: To study effect of neutrophilokines on functional activity of macrophages (Mph) during formation of immunity against cholera. MATERIALS AND METHODS: In order to obtain peritoneal neutrophils (Nph), 2 ml of 0.1% glycogen solution in buffered with phosphates sodium chloride solution was administered intraperitoneally to 100 outbred mice. Vibrio cholerae 1130 in dose 10 microbial cells/Nph and cholera toxin (CT) in dose 1 or 10 mcg/ ml were used as inducers of neutrophilokines synthesis. Obtained neutrophilokines were assessed on their effect on phagocytic activity of Mph, resistance of these cells to cytotoxic and apoptogenic effects of Vibrio cholerae and CT as well as effect on lysosomal apparatus of Mph. RESULTS: It was established that neutrophilokines induced by Vibrio cholerae and CT stimulate killer activity of Mph and lability of their lysosomal membranes, and suppress programmed death of these cells. CONCLUSION: Results of studies revealed immunoregulatory activity of neutrophilokines relative to Mph and demonstrated ability for cooperation between mono- and polynuclear phagocytes mediated by cytokines and, in particular, neutrophilokines.
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Toxina del Cólera/inmunología , Cólera/inmunología , Citocinas/biosíntesis , Macrófagos Peritoneales/inmunología , Neutrófilos/inmunología , Vibrio cholerae/inmunología , Animales , Apoptosis/inmunología , Lisosomas/inmunología , Ratones , Fagocitosis/inmunologíaRESUMEN
A procedure was proposed to evaluate the immunoregulatory activity of neutrophilokine fractions on a model of macrophages. It was established that all the fractions studied did not affect the absorptive capacity of these cells in both primary and secondary immune responses. At the same time, the majority of neutrophilokine fractions modulated the killer activity of macrophages: they potentiated or inhibited it. The proposed procedure for evaluating the regulatory effect of individual neutrophilokine fractions on a model of studying the killer activity makes it possible not only to characterize their activity, but also to identify helper and suppressor fractions, which discloses approaches to correcting an immune response by means of these fractions.
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Citocinas/inmunología , Macrófagos Peritoneales/inmunología , Neutrófilos/inmunología , Animales , Células Asesinas Inducidas por Citocinas/inmunología , Citocinas/metabolismo , Activación de Macrófagos , Macrófagos Peritoneales/metabolismo , Ratones , Neutrófilos/metabolismo , Fagocitosis , Vacuna contra la Peste/inmunología , Yersinia pestis/inmunologíaRESUMEN
Results of experimental study of regulatory effect of nutrophilokines induced by Yersinia pestis EV strain on population and subpopulation repertoire of lymphocytes and their functional activity during immune response against plague infection are presented. It was established that these neutrophilokines stimulate CD4+ and suppress CD8+ lymphocytes. Helper effect of neutrophilokines on functional activity of lymphocytes was more pronounced during secondary than during primary immune response.
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Citocinas/inmunología , Neutrófilos/inmunología , Vacuna contra la Peste/inmunología , Peste/inmunología , Yersinia pestis/inmunología , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Citocinas/biosíntesis , Citotoxicidad Inmunológica , Activación de Linfocitos , Recuento de Linfocitos , RatonesRESUMEN
AIM: To study the role of active programmed cell death induced by Vibrio cholerae antigens in alteration of peritoneal macrophages of experimental animals. MATERIALS AND METHODS: Apoptosis was assessed by cytofluorometric analysis with propidium iodide using cytofluorometer "Coulter" as well as on characteristic morphological changes of cells in stained histological preparations. RESULTS: Performed experiments carried out by both methods provide evidence that V. cholerae and its antigens (cholera toxin, neuraminidase, chitinase, and lypopolysaccharide) cause apoptosis of mice peritoneal macrophages, which leads to their alteration. CONCLUSION: Our results demonstrate that programmed cell death of phagocytes is one of the causes of cytotoxic effect of V.cholerae and its antigens. Performed experiments show the role of apoptosis of macrophages in formation of postimmunization immunosuppression after vaccination against cholera.
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Apoptosis/inmunología , Toxina del Cólera/inmunología , Cólera/inmunología , Macrófagos/inmunología , Vibrio cholerae/inmunología , Animales , Antígenos Bacterianos/inmunología , Pruebas Inmunológicas de Citotoxicidad , RatonesRESUMEN
The transcription factor E2F1 plays key roles in skin homeostasis, and is essential for normal keratinocyte proliferation and epidermal regeneration after injury. We have previously established that, in differentiating keratinocytes, E2F1 activity is controlled by nuclear export and subsequent degradation. These events are triggered by differentiation-induced stimulation of protein kinase C and p38 mitogen-activated protein kinase (MAPK). However, the mechanisms that induce E2F1 export from the nucleus and the role of p38 MAPK in this process are poorly understood. We now describe a novel regulatory pathway for E2F1, which involves phosphorylation by p38. We demonstrate that E2F1 forms complexes with active p38 through regions that exclude the N-terminus of this transcription factor, and that p38 activity is a major contributor to the phosphorylation status of E2F1 in keratinocytes. Using in vitro kinase assays, we identified Ser403 and Thr433 as the residues phosphorylated by p38. The biological significance of these observations is underscored by the inability of E2F1 mutants lacking one or both of these residues to be exported from the nucleus and degraded when keratinocytes receive differentiation stimuli, which results in impaired keratinocyte maturation.
Asunto(s)
Diferenciación Celular , Factor de Transcripción E2F1/metabolismo , Queratinocitos/citología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Línea Celular , Análisis Mutacional de ADN , Factor de Transcripción E2F1/genética , Queratinocitos/metabolismo , Ratones , Fosforilación , Eliminación de Secuencia , Serina/genética , Serina/metabolismo , Treonina/genética , Treonina/metabolismoRESUMEN
Biochemical and immunobiologic characteristics of fractions of neutrophilokines during primary and secondary immune response against plague infection are presented. Fractions were obtained using gel chromatography from neutrophilokines complex induced by vaccine strain of Yersinia pestis. It was revealed that fractions of neutrophilokines regulate IL-2 synthesis by Th1-helpers, IL-4 and IL-5 synthesis by Th2-helpers and also expression of IL-2 receptors by immunocompetent cells. Helper effect of neutrophilokines' fractions was more pronounced during secondary immune response.
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Citocinas/inmunología , Neutrófilos/inmunología , Peste/inmunología , Yersinia pestis/inmunología , Animales , Cromatografía en Gel , Citocinas/química , Citocinas/aislamiento & purificación , Inmunización , Inmunización Secundaria , Ratones , Peso Molecular , Receptores de Interleucina-2/biosíntesis , Bazo/inmunología , Células TH1/inmunología , Células Th2/inmunología , Timo/inmunologíaRESUMEN
E2F factors modulate a plethora of cell functions, including proliferation, differentiation, DNA repair and apoptosis. We have shown that differentiation in primary epidermal keratinocytes leads to E2F1 downregulation via activation of protein kinase C and p38 mitogen-activated protein kinase. We now demonstrate that E2F1 downregulation in differentiating keratinocytes involves its ubiquitination, as well as proteasomal degradation subsequent to CRM1-dependent nuclear export. E2F1 nuclear export specifically in response to differentiation requires regions adjacent to the cyclin A-binding domain in the N-terminus of this protein. Significantly, inhibition of p38 interferes with nuclear export and degradation of E2F1 during differentiation, but has no effect on E2F1 in undifferentiated cells. Thus, induction of differentiation in epidermal keratinocytes activates a specific program for post-transcriptional downregulation of E2F1, which involves signaling through p38 and activation of nuclear export pathways.
Asunto(s)
Diferenciación Celular/genética , Núcleo Celular/metabolismo , Factor de Transcripción E2F1/metabolismo , Carioferinas/metabolismo , Queratinocitos/citología , Receptores Citoplasmáticos y Nucleares/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Transporte Activo de Núcleo Celular , Animales , Núcleo Celular/química , Células Cultivadas , Citoplasma/química , Citoplasma/metabolismo , Regulación hacia Abajo , Factor de Transcripción E2F1/análisis , Factor de Transcripción E2F1/genética , Activación Enzimática , Queratinocitos/química , Queratinocitos/metabolismo , Ratones , Mutación , Complejo de la Endopetidasa Proteasomal/metabolismo , Estructura Terciaria de Proteína , Transducción de Señal , Ubiquitina/metabolismo , Proteína Exportina 1RESUMEN
E2F transcription factors regulate proliferation, differentiation, DNA repair and apoptosis. Tight E2F regulation is crucial for epidermal formation and regeneration. However, virtually nothing is known about the molecular events modulating E2F during epidermal keratinocyte differentiation. Elucidation of these events is essential to understand epidermal morphogenesis, transformation and repair. Here we show that, in differentiating keratinocytes, Ca(2+)-induced protein kinase C (PKC) activation downregulates E2F1 protein levels. Further, we have identified PKC delta and eta as those isoforms specifically involved in induction of E2F1 proteasomal degradation. We also demonstrate that E2F1 downregulation by novel PKC isozymes requires activation of p38beta mitogen-activated protein kinase (MAPK). This is the first example of regulation in the E2F transcription factor family by activation of PKC and MAPK in the context of biologically significant differentiation stimuli in epithelia.
Asunto(s)
Diferenciación Celular , Factor de Transcripción E2F1/metabolismo , Queratinocitos/citología , Proteína Quinasa C/metabolismo , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Activación Enzimática , Queratinocitos/enzimología , Queratinocitos/metabolismo , RatonesRESUMEN
An automated hematological analyzer, prototype of a quick microbiological diagnostics system, was tested positively for the ability to differentiate microbial cells (six test-strains with different morphological and tinctorial properties) by geometry and dye intensity.
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Procesamiento Automatizado de Datos , Microbiología/instrumentación , Humanos , Microscopía/instrumentaciónRESUMEN
The evaluation of the complex of neutrophilokines whose synthesis was induced by Yersinia pestis vaccine strain EV on the production of lymphokines in the process of the formation of primary and secondary immunity to plague is presented. As revealed in this study, neutrophilokines regulate the synthesis of IL-2 by T helpers of type 1, IL-4 and IL-5 by T helpers of type 2, IL-1 by B lymphocytes, as well as the expression of receptors IL-2 by immunocompetent cells. The helper effect of neutrophilokines is more pronounced in the secondary immune response.
Asunto(s)
Citocinas/farmacología , Linfocinas/biosíntesis , Neutrófilos/inmunología , Peste/inmunología , Yersinia pestis/inmunología , Animales , Linfocitos B/inmunología , Vacunas Bacterianas/inmunología , Citocinas/aislamiento & purificación , Inmunidad Celular , Inmunización , Interleucina-1/biosíntesis , Interleucina-2/biosíntesis , Interleucina-4/biosíntesis , Interleucina-5/biosíntesis , Ratones , Peste/sangre , Peste/prevención & control , Receptores de Interleucina-2/metabolismo , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
In experiments on isolated rat and rabbit right atrium, a new class III antiarrhythmic drug RG-2 (0,01-1 microM) was shown to have anticholinergic action competing with 0.2-1 mM carbachol. RG-2 (0.1-1 microM) produced dose-dependent increase of APD90% in rat and rabbit atrial cells and had no effects on other action potential parameters. In presence of carbachol RG-2 produced significantly greater increase of APD90% and caused significant increase of APD50%. Thus RG-2 exerts anticholinergic action, which can take important part in RG-2 antiarrhythmic activity.
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Antiarrítmicos , Atrios Cardíacos , Potenciales de Acción/efectos de los fármacos , Animales , Antiarrítmicos/farmacología , Antagonistas Colinérgicos , Atrios Cardíacos/efectos de los fármacosRESUMEN
The purpose of the case study was elaboration of methods for removing the false-positive results in the detection of virus antigens that cause acute respiratory lesions both in the plane and dot-membrane variations of immune-enzyme assays of monoclonal antibodies. Modeled experiments showed that the non-specific staining of biological samples, in which the above viral antigen are looked for, is preconditioned by a direct reaction of the substrate with its own oxidizing enzymes and by the binding of monoclonal antibodies with biological macromolecules free of any viral adherence and sorbated in the solid phase. Approaches to solving such issues are described in the paper. They comprise the inhibition of the own oxidizing activity of wash-outs by the substrate and the application of detergents. Different detergents were comparatively analyzed and the optimal compounds were chosen for each variation of immune-enzyme test-systems. The described techniques ensure more reliable results in the viral antigen detection by immune-enzyme assay.
Asunto(s)
Anticuerpos Monoclonales/química , Detergentes/química , Técnicas para Inmunoenzimas/métodos , Animales , Reacciones Cruzadas , Células HeLa , Hemaglutininas Virales/análisis , Humanos , Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/análisis , Ratones , Polisorbatos/químicaRESUMEN
The results of the comparative analysis of the cytokine inducing activity of Yersinia pestis EV antigens are presented. Y. pestis fraction 1A (F1A) and lipopolysaccharide (LPS) were shown to induce mono- and neutrophilokines, regulating cooperative interaction of phagocytes in the process of immunity formation to plague. Neutrophilokines and monokines exceed in their capacity for inducing F1A such acknowledged inductor as Escherichia coli LPS. As revealed by the comparative evaluation of Y. pestis EV LPS and E. coli LPS, neutrophilokines synthesized under the action of the former preparation, have greater influence on the inhibition of the macrophage migration from the infection focus as well as on digestive activity of these cells (in secondary immune response) and on the labilization of the lysosome membranes of macrophages than neutrophilokines induced by E. coli LPS. At the same time they produce a lesser modulating effect on the killer and chemotactic activity of neutrophils, as well as on the expression of FC receptors (FcR) on their surface in comparison with monokines, synthesized under the influence of E. coli LPS.
Asunto(s)
Antígenos Bacterianos/inmunología , Citocinas/biosíntesis , Yersinia pestis/inmunología , Animales , Recuento de Células , Movimiento Celular , Citocinas/inmunología , Cobayas , Humanos , Lipopolisacáridos/farmacología , Lisosomas/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Fagocitosis , Receptores Fc/análisisRESUMEN
A study was made of the Yersinia pestis EV induced monokine complex influence on neutrophil (Nph) functional activity in the course of antiplague immunity formation. The obtained monokines essentially enhance Nph killing, chemotactic activities and Fc-receptor expression, and stimulate lysosome membrane labilization of these cells. The helper effect of the Y. pestis EV induced monokines on Nph functional activity is more pronounced during the secondary immune response, than in the course of the primary one.