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Lassa virus: characterization of infectious agent, biological models for pathogenesis studies and variants of vaccine 拉沙病毒:传染因子的特征、发病机制研究的生物学模型和疫苗变体
Pub Date : 2021-02-26 DOI: 10.15789/1563-0625-LVC-2060
E. I. Kazachinskaya, V. S. Aripov, A. V. Zaikovskaya, A. Shestopalov
Lassa virus (LASV) is classified into genus Mammarenavirus of Arenaviridae family. This virus is etiological agent of Lassa fever (LF) which is widespread in Africa. On average, in four out of five infected people, LF occurs without symptoms. The annual incidence ranges from 100,000 to 500,000 registered clinical cases, at a mortality rate of 1-2%. Among hospitalized patients with severe symptoms of hemorrhagic fever, this figure may be from 14 to 89.5%. Signs of an adverse outcome in LF are open bleeding and disorders of CNS (convulsions, tremor, disorientation and coma). Death occurs from multiple organ failure. Severely ill people recover slowly and may have relapses and complications such as pneumonia, myocarditis, psychosis, and hearing loss.Transmission of the virus in endemic territories occurs by alimentary way, air-dust and airborne droplets from a zoonotic source – rodents of the species African multimammate rat (Mastomys natalensis), by accidental contacts of people with their secretions (urine, feces, saliva) as well as when butchering carcasses and eating rodents. These animals are characterized by asymptomatic carrier and life-long persistence of the virus. Cases of transmission of the virus from person to person through the blood or other body fluids of patients are described. A sick person is contagious for two months, because the virus circulates in the blood despite high levels of antibodies. Infection of medical staff occurs during emergency surgical operations, or when the rules of contact precautions are not observed. Currently, with the ongoing LF outbreak in Nigeria, since 2016, hospitals have registered mortality rates of 22 and 8% for patients and health workers, respectively. During 1969-2016, 33 imported cases of this disease were described from West Africa to non-endemic territories (in the USA, Canada, Great Britain, the Netherlands, Germany, Israel and Japan). The mortality rate among these patients was 39%.The lack of prophylactic vaccines and specific therapeutic drugs is the major challenge for the prevention of LF. Thus, this review considers biological models (cell cultures and animals) that are suitable for studying the pathogenesis of this disease, preclinical studies of the specific activity and harmlessness of candidate vaccines, as well as options for these developments based on the platforms such as inactivated LASV and its DNA, the reassortant of Mopeia arenavirus, and measles virus attenuated strains, recombinant and replication-defective viruses (smallpox vaccine, Venezuelan equine encephalitis, bovine vesicular stomatitis, adenovirus of chimpanzee) and virus-like particles.
拉沙病毒(LASV)属于沙病毒科母沙病毒属。该病毒是在非洲广泛传播的拉沙热(LF)的病原体。平均而言,在五分之四的感染者中,LF没有症状。年发病率在10万至50万登记临床病例之间,死亡率为1-2%。在有严重出血热症状的住院患者中,这一数字可能在14%至89.5%之间。LF不良结局的迹象是开放性出血和中枢神经系统障碍(抽搐、震颤、定向障碍和昏迷)。多器官衰竭导致死亡。病情严重的人恢复缓慢,可能会有复发和并发症,如肺炎、心肌炎、精神病和听力丧失。该病毒在流行地区的传播是通过食物方式、空气粉尘和人畜共患源——非洲多母鼠(Mastomys natalensis)的啮齿动物——的空气飞沫,通过意外接触人类的分泌物(尿液、粪便、唾液)以及在屠宰啮齿动物尸体和食用啮齿动物时发生。这些动物的特点是无症状携带者和终生存在病毒。描述了病毒通过患者血液或其他体液在人与人之间传播的病例。病人的传染性持续两个月,因为尽管抗体水平很高,病毒仍在血液中循环。医务人员感染发生在紧急外科手术期间,或未遵守接触预防规则时。目前,随着尼日利亚自2016年以来持续爆发的LF疫情,医院登记的患者和卫生工作者死亡率分别为22%和8%。1969-2016年期间,报告了从西非向非流行地区(美国、加拿大、英国、荷兰、德国、以色列和日本)输入的33例该病病例。这些患者的死亡率为39%。缺乏预防性疫苗和特异性治疗药物是预防LF的主要挑战。因此,本综述考虑了适合研究该病发病机制的生物学模型(细胞培养和动物)、候选疫苗特异性活性和无害性的临床前研究,以及基于灭活LASV及其DNA、莫皮亚沙粒病毒和麻疹病毒减毒株重组、重组和复制缺陷病毒(天花疫苗、委内瑞拉马脑炎、牛水疱性口炎,黑猩猩腺病毒)和病毒样颗粒。
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引用次数: 0
Популяционный состав CD4 + 5RA/ CD4 + 5RO позитивных T-лимфоцитов и цитокиновый профиль у детей с аллергическими респираторными заболеваниями 阳性T淋巴细胞CD4+5RA/CD4+5RO的人群组成和过敏性呼吸道疾病儿童的细胞因子特征
Pub Date : 2021-02-26 DOI: 10.15789/1563-0625-PCO-2009
А И Турянская, Н. Г. Плехова, В А Сабыныч, Е. В. Просекова
The changing states of T cell populations responsible for the chronic course of allergic inflammation and diseases, including allergic bronchial asthma, are not yet sufficiently characterized. The aim of this study was to detect phenotypic changes in the CD45RA/CD45RO positive T lymphocytes and the level of regulatory cytokines (TNFα, IFNγ, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17А, IL-17F) in allergic respiratory diseases (ARD) in children. In blood of 90 children aged 3-11 (60 children with ARD and 30 healthy peers) were studied of the immune cellular populations and cytokine indices. The levels of IL-4, IL-8, IL-10, IL-13, IL-17A and IL-17F in blood serum of children with bronchial asthma and allergic rhinitis differed from appropriate indices in control group (p = 0.001). The quantity of CD3 + CD8 + CD45RACD45RO + cells, T helpers (p < 0.05) and Th effectors simultaneously expressing both isoforms of the CD45RA + and CD45RO receptor in peripheral blood of children with ARD significantly exceeded those in control group (p < 0.001). In healthy children, Th17 population (CD3 + CD4 + CD196 lymphocytes) comprised 9.49±1.6% of CD3 + CD4 + of cells, the number of such lymphocytes was significantly increased to 14.5±0.77 in children with allergic diseases (p < 0.001). Absolute numbers of Th17+ cells were 93.0±9.30 and 127,0±72.0 cells/µl respectively (p = 0.002). Indicators of CD4CD45RO positive memory cells in children with ARD was determined as significantly lower (p < 0.001), whereas quantity of CD3 + CD19 + proved to be higher (p < 0.05) than in healthy peers. Absolute counts of these cells did not differ between the groups. The number of CD8 + CD45RO + T lymphocytes was significantly higher in children with allergic diseases (p < 0.025). This research shows that the quantitative ratio of CD3 + CD8 + CD45RA + and CD3 + CD8 + CD45RO + populations of T cells, and increased levels of cytokines, synthesizable via Th2 and Th17, in peripheral blood may be helpful for understanding genesis of allergic respiratory diseases, and extends our knowledge on immune mechanisms of allergic disorders for individualization of therapeutic programs.
负责过敏性炎症和疾病(包括过敏性支气管哮喘)慢性病程的T细胞群的变化状态尚未充分表征。本研究旨在检测儿童变应性呼吸系统疾病(ARD)患者CD45RA/CD45RO阳性T淋巴细胞及调节细胞因子(TNFα、IFNγ、IL-4、IL-6、IL-8、IL-10、IL-13、IL-17А、IL-17F)水平的表型变化。对90例3 ~ 11岁儿童(60例ARD患儿和30例健康儿童)血液中免疫细胞群和细胞因子指标进行了研究。支气管哮喘和变应性鼻炎患儿血清IL-4、IL-8、IL-10、IL-13、IL-17A、IL-17F水平与对照组比较差异有统计学意义(p = 0.001)。ARD患儿外周血中同时表达CD45RA +和CD45RO受体两种亚型的CD3 + CD8 + CD45RACD45RO +细胞、T辅助细胞(p < 0.05)和T效应细胞数量显著高于对照组(p < 0.001)。在健康儿童中,Th17群(CD3 + CD4 + CD196淋巴细胞)占CD3 + CD4 +细胞总数的9.49±1.6%,变应性疾病儿童Th17淋巴细胞数量显著增加至14.5±0.77个(p < 0.001)。Th17+细胞的绝对数量分别为93.0±9.30和127.0±72.0个细胞/µl (p = 0.002)。与正常儿童相比,ARD患儿CD4CD45RO阳性记忆细胞指标明显降低(p < 0.001), CD3 + CD19 +水平明显升高(p < 0.05)。这些细胞的绝对计数在两组之间没有差异。变应性疾病患儿CD8 + CD45RO + T淋巴细胞数量显著增高(p < 0.025)。本研究表明,外周血中CD3 + CD8 + CD45RA +和CD3 + CD8 + CD45RO +群体的定量比例,以及通过Th2和Th17合成的细胞因子水平的升高,可能有助于了解过敏性呼吸系统疾病的发生,并扩展我们对过敏性疾病免疫机制的认识,为个体化治疗方案提供依据。
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引用次数: 0
In vitro phenotypic re-orientation of functionally important neutrophil subpopulations and their microbicidal activity in the children with purulent inflammatory diseases influenced by glucosaminil muramildipeptide 糖氨基muramildipeptide影响化脓性炎性疾病患儿中功能重要的中性粒细胞亚群的体外表型重定向及其杀微生物活性
Pub Date : 2021-02-26 DOI: 10.15789/1563-0625-IVP-2136
I. Nesterova, G. Chudilova, M. Mitropanova, V. Pavlenko, L. Lomtatidze, S. Kovaleva, V. Tarakanov, N. Barova
Numerous studies over last decade have shown that functional capacity of neutrophil granulocytes (NG) determines the course and outcome of many diseases. Identification of phenotypic variants of functionally significant NG subpopulations is a new approach allows us to assess the adequacy or deficiency of NG involvement into infectious inflammation processes at molecular level. An opportunity of reorienting a deficient NG subpopulational phenotype in purulent inflammatory diseases due to the rearrangement of the receptor set induced by various immunotropic substances may serve as a key to recovery of normal NG functioning. Our aim was to study the effect of glucosaminylmuramyldipeptide (GMDP) under in vitro conditions upon the phenotypic profile of four functionally significant subpopulations, i.e.,  CD62L + CD63 - NG, CD62L + CD63 + NG and CD64 - CD32 + CD16 + CD11b + NG, CD64 + CD32 + CD16 + CD11b + NG,  along with assessment of expression density of appropriate membrane molecules and NG microbicidal activity in the children with purulent inflammatory diseases. 90 samples of peripheral blood (PC) were taken from children 2 to 4 years old, including 12 children with minor purulent infection (MPI), and 7 children were studied as conditionally healthy controls. Their peripheral blood was incubated for 60 minutes at 37 °C with GMP (10 -6 g/l). Using flow cytometry technique, the relative numbers of some NG subpopulations, i.e.,  CD64 - CD16 + CD32 + CD11b + NG, CD64 + CD16 + CD32 + CD11b + NG, CD62L + CD63 - NG, CD62L + CD63 + NG  were evaluated, and the phenotype features of each subpopulation were investigated according to the density of appropriate membrane molecule expression (MFI). In parallel, phagocytic and microbicidal activity of NG was tested in these study groups. The obtained data indicate for presence of for distinct NG subpopulations, both in healthy children and in children with MPI. We have revealed phenotypic transformation of the four studied NG subpopulations from MPI patients including disturbed phagocytic and microbicidal functions of the cells. Using of this in vitro system, we have shown that the transformed phenotype of the four functionally significant NG subpopulations of MPI patients was re-arranged under GMDP treatment. At the same time, the number of  CD62L + CD63 + NG and CD64 - CD32 + CD16 + CD11b + NG  subpopulations was increased, along with decreased amounts of CD64 + CD32 + CD16 + CD11b + NG and CD62L + CD63 - NG subpopulations, being accompanied by restoration of microbicidal activity of NGs. The obtained data allow us to accomplish current understanding of immunotropic effects of GMDP, and to extend the potential scope of its experimental and clinical application. The new data on GMDP effects revealed by in vitro system, i.e. phenotype rearrangement of functionally significant NG subpopulations  CD64 - CD16 + CD32 + CD11b + , CD64 + CD16 + CD32 + CD11b + , CD62L + CD63 - , CD62L + CD63 +  in atypical purulent inf
近十年来的大量研究表明,中性粒细胞(NG)的功能能力决定了许多疾病的过程和结局。鉴定功能显著的NG亚群的表型变异是一种新的方法,使我们能够在分子水平上评估NG是否充分或缺乏参与感染性炎症过程。在化脓性炎症疾病中,由于各种免疫物质诱导的受体组重排,有机会重新定位缺乏的NG亚群表型,这可能是恢复正常NG功能的关键。我们的目的是在体外条件下研究葡萄糖胺基甲基二肽(GMDP)对四个功能显著的亚群CD62L + CD63 - NG、CD62L + CD63 + NG和CD64 - CD32 + CD16 + CD11b + NG、CD64 + CD32 + CD16 + CD11b + NG的表型谱的影响,并评估相应膜分子的表达密度和NG在化脓性炎症性疾病儿童中的杀微生物活性。采集2 ~ 4岁儿童外周血(PC) 90份,其中轻度化脓性感染(MPI)患儿12份,有条件健康对照7份。外周血在37℃下用GMP (10 -6 g/l)孵育60分钟。利用流式细胞术技术,对不同NG亚群(CD64 - CD16 + CD32 + CD11b + NG、CD64 + CD16 + CD32 + CD11b + NG、CD62L + CD63 - NG、CD62L + CD63 + NG)的相对数量进行分析,并根据适当膜分子表达密度(MFI)分析各亚群的表型特征。同时,在这些研究组中检测了NG的吞噬和杀微生物活性。所获得的数据表明,在健康儿童和MPI儿童中存在不同的NG亚群。我们已经揭示了MPI患者的四个研究NG亚群的表型转化,包括细胞的吞噬和杀微生物功能受到干扰。利用这种体外系统,我们已经证明MPI患者的四个功能显著的NG亚群的转化表型在GMDP治疗下被重新排列。同时,CD62L + CD63 + NG和CD64 - CD32 + CD16 + CD11b + NG亚群数量增加,CD64 + CD32 + CD16 + CD11b + NG和CD62L + CD63 - NG亚群数量减少,同时NG的杀微生物活性恢复。获得的数据使我们能够完成当前对GMDP免疫效应的理解,并扩大其实验和临床应用的潜在范围。在儿童非典型化脓性炎症性疾病中,通过体外系统揭示的GMDP效应的新数据,即功能显著的NG亚群CD64 - CD16 + CD32 + CD11b +、CD64 + CD16 + CD32 + CD11b +、CD62L + CD63 -、CD62L + CD63 +的表型重排,可能在未来用于开发针对MPI儿童NG功能障碍的创新免疫治疗策略。
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引用次数: 0
Profile of cytokines in aqueous humor and trabecular meshwork cell culture in patients with pseudoexfoliation glaucoma 假性脱落性青光眼患者房水和小梁网细胞培养中细胞因子的变化
Pub Date : 2021-02-26 DOI: 10.15789/1563-0625-POC-2097
V. V. Rakhmanov, A. Yuryeva, T. S. Varganova, D. Sokolov, S. Chepanov, K. Markova, Y. Astakhov, S. Astakhov, S. Selkov
Glaucoma is one of the leading causes of irreversible blindness worldwide, being an age-related disease. Its pathogenesis still is not fully understood. A particular interest is attracted to evaluation of the cytokine concentrations in the trabecular meshwork cell culture, and in the aqueous humor (AH) taken from the same patient, since such data may allow to describe more completely the glaucomatous trabecular changes and to clarify the mechanisms of intercellular interactions in pseudoexfoliative (PEX) glaucoma. The purpose of this study was a comparative analysis of cytokine contents in AH and in trabecular tissue (TT) supernatants in the patients with PEX glaucoma. The study included 23 eyes of patients with PEX glaucoma. The material studied was AH and supernatant of TT cell culture. The cytokine concentration was measured using a flow cytofluorimeter FacsCantoII (BD, USA) using the CBA method. SPSS version 19 software (IBM, USA) was used for the statistical data processing. Concentrations of cytokines (TNFα, IFNγ, IL-1β, IL-6, IL-8, IL- 10, VEGF, GM-CSF) were determined in AH and in the TT supernatant for each of the patients with PEX glaucoma. Only IL-6 and VEGF concentrations in AH were higher than those in the TT supernatant in patients with PEX glaucoma. The IL-6 concentration positively correlated with the VEGF and IL-8 concentrations in the TT supernatant. Correlations between other cytokines in the TT supernatant and AH were also identified and analyzed. Multiple regression analysis revealed that the duration of glaucoma and the IFNγ and TNFα concentrations in AH may have a significant influence on the corneal endothelial cells, being associated with density reduction in patients with PEX glaucoma. The correlation analysis did not reveal any links between other clinical data (corneal thickness in the optical center, IOP level, age) and the cytokine concentrations in the studied tissues. The obtained results suggest that only simultaneous analysis of the cytokine concentrations in the TT supernatant and AH taken from the same patient may provide a more complete description of the cytokine imbalance and pathological processes occurring in the trabecular meshwork in PEX glaucoma patients. It has been shown that the changing cytokine ratios observed in PEX glaucoma may be associated with development of uniform structural and functional changes in all tissues of the anterior eye segment.
青光眼是一种与年龄有关的疾病,是世界范围内导致不可逆失明的主要原因之一。其发病机制尚不完全清楚。对小梁网状细胞培养和同一患者房水(AH)中细胞因子浓度的评估引起了特别的兴趣,因为这些数据可以更完整地描述青光眼小梁的变化,并阐明假脱落性青光眼(PEX)细胞间相互作用的机制。本研究的目的是比较分析PEX型青光眼患者AH和小梁组织(TT)上清中细胞因子的含量。该研究包括23只PEX型青光眼患者的眼睛。所研究的材料为AH和TT细胞培养的上清。使用流式细胞荧光仪FacsCantoII (BD, USA)采用CBA法测定细胞因子浓度。采用SPSS version 19软件(IBM, USA)进行统计数据处理。测定每例PEX型青光眼患者AH和TT上清液中细胞因子(TNFα、IFNγ、IL-1β、IL-6、IL-8、IL- 10、VEGF、GM-CSF)的浓度。PEX型青光眼患者AH中仅有IL-6和VEGF浓度高于TT上清。TT上清中IL-6浓度与VEGF、IL-8浓度呈正相关。TT上清液中其他细胞因子与AH的相关性也被鉴定和分析。多元回归分析显示,青光眼持续时间和AH中IFNγ和TNFα浓度可能对PEX型青光眼患者角膜内皮细胞有显著影响,与角膜内皮细胞密度降低有关。相关性分析没有显示其他临床数据(视中心角膜厚度、IOP水平、年龄)与研究组织中细胞因子浓度之间的任何联系。上述结果提示,只有同时分析同一患者TT上清和AH中的细胞因子浓度,才能更完整地描述PEX青光眼患者小梁网中细胞因子失衡和病理过程。研究表明,在PEX型青光眼中观察到的细胞因子比率的变化可能与前眼段所有组织的均匀结构和功能变化的发展有关。
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引用次数: 0
Immunological context of brain injury 脑损伤的免疫学背景
Pub Date : 2021-02-26 DOI: 10.15789/1563-0625-ICO-2011
N. Plekhova, I. Radkov, S. Zinoviev, V. B. Shumatov
The parameters of several populations of immune cells (T cell populations, macrophage subpopulations) in peripheral blood and brain were studied in a clinically significant model of mild traumatic brain injury among rats. The population of resident cells of innate immunity of microglia and brain astrocytes with local tissue damage is involved in the implementation of the inflammatory response, it is also shown that in case of trauma, blood leukocytes can overcome the blood-brain barrier and penetrate the brain parenchyma. The methods of flow cytometry and immunofluorescence were used. An increase in the number of monocytes and neutrophils up to 1 day, after a mild traumatic brain injury (TBI) with a subsequent decrease to the end of the observation period was noticed. It was determined, that the number of CD45+ cells, CD3+T cells decreased at 1 days post-injury (dpi), and rose slightly by 14 dpi, the percentage of CD4+T cells continuously declined from 7 to 14 dpi, while the percentage of CD8+T cells increased from 7 to 14 dpi. With mild traumatic brain injury in animals, a significant (3-10 times) decrease in the number of microvessels with a positive reaction to the presence of SMI 71 on the 8th and 14th day after head injury was observed. Intensive staining of SMI 71 microvessels was sometimes observed with an increase in the area of a positive reaction. Thin positive deposits of the reaction product are observed in the brain of healthy animals around the wall of the microvessel. In the damaged brain, CD45high/CD11b+ positive macrophages of the M1 subpopulation appeared in the brain tissue on the 2nd day after TBI and a significant amount was observed on the 8-14th day. In the corpus callosum and ipsilateral region of the striatum, the content of cells expressing CD16/11b+ reached a maximum 8 days after TBI, which correlated with a decrease in the positive response to the presence of endothelial antigen SMI 71. Thus, in the acute period of mild TBI, the presence of neuroimmunopathological processes is determined in the brain, which can subsequently result to the dysregulation of neuroimmune connections.
在具有临床意义的大鼠轻度创伤性脑损伤模型中,研究了外周血和脑中几种免疫细胞群(T细胞群、巨噬细胞亚群)的参数。局部组织损伤的小胶质细胞和脑星形胶质细胞的固有免疫驻留细胞群参与了炎症反应的实施,也表明在创伤情况下,血白细胞可以克服血脑屏障并穿透脑实质。采用流式细胞术和免疫荧光法。在轻度创伤性脑损伤(TBI)后1天内,单核细胞和中性粒细胞数量增加,随后在观察期结束时下降。结果表明,CD45+细胞、CD3+T细胞数量在损伤后1天(dpi)下降,并小幅上升14 dpi, CD4+T细胞百分比从7 - 14 dpi持续下降,而CD8+T细胞百分比从7 - 14 dpi持续上升。在轻度颅脑损伤动物中,观察到SMI 71在颅脑损伤后第8天和第14天呈阳性反应的微血管数量明显减少(3-10倍)。smi71微血管的强化染色有时观察到阳性反应面积的增加。在健康动物的大脑微血管壁周围观察到薄的阳性反应产物沉积。损伤脑组织中CD45high/CD11b+阳性巨噬细胞M1亚群出现于TBI后第2天,并在第8-14天大量出现。在胼胝体和纹状体同侧区,表达CD16/11b+的细胞含量在脑损伤后8天达到最大值,这与内皮抗原SMI 71存在的阳性反应减少有关。因此,在轻度TBI的急性期,大脑中神经免疫病理过程的存在是确定的,这可能随后导致神经免疫连接的失调。
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引用次数: 0
Opportunities for immunocorrection aiming for reduction of morbidity in the areas with adverse occupational and environmental conditions 免疫矫正的机会,目的是在有不良职业和环境条件的地区减少发病率
Pub Date : 2021-01-10 DOI: 10.15789/1563-0625-ofi-2055
S. Petlenko, E. Golovacheva, O. Afanasieva
Previous studies have shown that prolonged professional contact with chemical xenobiotics contributes to sensitization of immune system and development of typical immunopathological processes, i.e., allergies and autoimmune diseases. Origin and severity of immune system disorders depends on the spectrum and duration of exposure to adverse factors and patterns of professional activity at the chemically hazardous facilities. The study of structural and functional changes in cellular, humoral and some factors of innate immunity in people working and living in areas with unfavorable environmental conditions revealed a number of immunological disorders that can be characterized as secondary immunodeficiency conditions, which may manifest with increased frequency of acute respiratory infections and other chronic diseases. Much attention is given to prevention and treatment of secondary immunodeficiency conditions, which are associated with decreased numbers of lymphocytes expressing CD3, CD4, CD8. The purpose of the study was determined by recent positive experience of using highly effective drugs based on thymic regulatory peptides affecting various steps of homeostasis, in order to correct immune disorders caused by exposure to radiation and other toxic substances. The aim of this study was to evaluate changes in immunity and effectiveness of immune correction by means of immunotropic drugs, i.e., Thymogen nasal spray, and Cytovir-3 capsules, in the cohorts living and working under the conditions of heavy chemical exposure. We observed 249 persons aged 18 years to 63 years recruited from the employees of the “Polygon “Krasny Bor” State Enterprise. The people had longterm professional contacts with the components of industrial toxic waste were under examination. Group 1 consisted of the administration staff, group 2 included drivers of special cargo transport. The control group consisted of 137 employees at the car enterprises in Saint Petersburg. The duration of follow-up observation was 1 year. The patients with a detected decrease in cellular immunity received immunotropic drugs based on alpha-glutamyl-tryptophan (Thymogen nasal spray dosed (Thymogen, 62 persons), or combined encapsuleted Cytovir-3 drug (Cytovir, 31 cases). 14 days after finishing the course, a second immunological study was conducted. Following the immunotropic therapies, the subjects showed an increase in relative content of CD3+, CD4+, and CD8+subpopulations, normalization of functional oxygen-dependent metabolism of polymorphonuclear neutrophil granulocyte system in the NBT test, as well as harmonization of the content of serum immunoglobulin contents. The one-year follow-up showed high effectiveness of these drugs, as shown by decreased incidence of acute infectious and lower exacerbation rates of chronic respiratory and gastrointestinal diseases. For the group 1 with working experience of 1 to 5 years, the persons who received Thymogen exhibited lower incidence of acute respi
先前的研究表明,长期接触化学外源药物会导致免疫系统的致敏和典型免疫病理过程的发展,即过敏和自身免疫性疾病。免疫系统紊乱的起因和严重程度取决于接触有害因素的范围和持续时间,以及化学危险设施的专业活动模式。在环境条件不利的地区工作和生活的人群中,对先天免疫细胞、体液和某些因素的结构和功能变化的研究揭示了一些可表征为继发性免疫缺陷状况的免疫紊乱,其表现可能是急性呼吸道感染和其他慢性疾病的频率增加。继发性免疫缺陷疾病与表达CD3、CD4、CD8的淋巴细胞数量减少有关,人们对继发性免疫缺陷疾病的预防和治疗给予了很大的关注。这项研究的目的是根据最近使用基于胸腺调节肽的高效药物的积极经验确定的,这些药物影响体内平衡的各个步骤,以纠正暴露于辐射和其他有毒物质引起的免疫紊乱。本研究的目的是评估在重化学暴露条件下生活和工作的队列中,免疫增强药物(如胸腺原鼻喷雾剂和细胞vir3胶囊)的免疫变化和免疫纠正的有效性。我们观察了从“Polygon”Krasny Bor国营企业雇员中招募的249名年龄在18至63岁之间的人。与工业有毒废物成分有长期职业接触的人员正在接受检查。第一组包括行政人员,第二组包括特殊货物运输的司机。对照组由圣彼得堡汽车企业的137名员工组成。随访观察1年。检测到细胞免疫功能下降的患者给予以α -谷氨酰色氨酸为主的促免疫药物(Thymogen鼻喷剂,62例)或联合包封的Cytovir-3药物(Cytovir, 31例)。疗程结束后14天,进行第二次免疫学研究。在免疫治疗后,受试者的CD3+、CD4+和CD8+亚群的相对含量增加,NBT试验中多形核中性粒细胞系统的功能性氧依赖代谢正常化,血清免疫球蛋白含量趋于一致。一年的随访显示,这些药物的有效性很高,急性感染性疾病的发生率降低,慢性呼吸道和胃肠道疾病的加重率降低。对于具有1至5年工作经验的第1组,接受胸腺原治疗的人表现出较低的急性呼吸道病毒感染发生率(减少37%),如支气管肺疾病的发生率较低(比基线低25%)。长期在不利地区工作的患者(第二组),接受胸腺原治疗后,急性呼吸道疾病发病率降低了4倍,其他呼吸道疾病发病率降低了1.5倍,消化器官疾病发病率降低了1.75倍。在第一组和第二组工作经验达1年的人员中,接种了Cytovir-3后,SARS发病率分别下降了1.95倍和2.0倍。结果表明,及时发现复杂有害化学因素引起的免疫系统紊乱,并给予选择性免疫纠正治疗,可减少在不利环境下工作的人的急慢性发病率。
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引用次数: 0
Russian-language adaptation of the international nomenclature of International Consensus on Antinuclear Antibody (ANA) Patterns (ICAP) 抗核抗体(ANA)模式国际共识国际命名法的俄语改编
Pub Date : 2021-01-10 DOI: 10.15789/1563-0625-rvo-2067
O. Tkachenko, S. Lapin, A. Mazing, A. Totolian
Antinuclear antibodies (ANAs) represent a spectrum of autoantibodies targeted for various nuclear and cytoplasmic components of the cells. Indirect immunofluorescence assay (IIF) is the main detection method for “antinuclear factor”. A positive ANA test is usually reported as a titer and a pattern of fluorescence. The ANA patterns refers to the distribution of staining produced by antibodies that react with antigens located in nucleus and cytoplasm of HEp-2 cells. To standardize nomenclature and descriptions of the various fluorescence patterns of antinuclear factor (ANF), the Initiative of the International Consensus on ANA Patterns (ICAP) group was developed in 2014. The aim of ICAP is to promote consensus regarding nomenclature of ANA patterns, a microphotograph database, as well as classification depending on the employee skills. Information on the main characteristics, as well as specific clinical associations of the patterns is available at www.ANApatterns.org. In ANA classification trees, the patterns are indicated by the #AC (anticell pattern) alphanumeric code, being divided into nuclear, cytoplasmic and mitotic groups. Depending on the clinical significance and/or ease of recognition, this nomenclature focuses on the differences between the patterns described by specialists at competent and expert levels. Of the nuclear types, the most significant are homogeneous, speckled, dense fine-speckled, centromere, nucleolar, nuclear dots. The cytoplasmic types may be discerned into fibrillar, speckled, mitochondrial, Golgi, rods and rings. On leaders, behalf of the ICAP translation team is headed by the Full Member of Russian Academy of Sciences, Professor A.A. Totolian, under the auspices of the Russian Research Society of Immunologists. In this article, we present the Russianlanguage adaptation of the ICAP nomenclature, in order to ensure unification and standardization of ANA detection results in the patients with autoimmune diseases.
抗核抗体(anti - nuclear antibodies, ANAs)是针对细胞的各种核和细胞质成分的一系列自身抗体。间接免疫荧光法是检测“抗核因子”的主要方法。ANA试验阳性通常报告为滴度和荧光模式。ANA模式是指抗体与HEp-2细胞细胞核和细胞质中的抗原发生反应后产生的染色分布。为了规范抗核因子(ANF)各种荧光模式的命名和描述,2014年制定了抗核因子(ANF)模式国际共识倡议(ICAP)小组。ICAP的目的是促进关于ANA模式命名的共识,一个显微照片数据库,以及根据员工技能的分类。有关这些模式的主要特征以及具体临床关联的信息可在www.ANApatterns.org上获得。在ANA分类树中,模式由#AC(反细胞模式)字母数字代码表示,分为核群、细胞质群和有丝分裂群。根据临床意义和/或易识别性,本命名法侧重于专家在胜任水平和专家水平上描述的模式之间的差异。在核类型中,最重要的是均匀型、斑点型、密集细斑点型、着丝粒型、核仁型和核点型。细胞质类型可分为纤维状、斑点状、线粒体、高尔基体、棒状和环状。在俄罗斯免疫学家研究学会的主持下,俄罗斯科学院正式成员A.A. Totolian教授代表ICAP翻译小组。在这篇文章中,我们提出了ICAP命名法的俄文改编,以确保自身免疫性疾病患者ANA检测结果的统一和标准化。
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引用次数: 0
Interaction of bacterial extracellular microvesicles with eukaryotic cells. 细菌胞外微泡与真核细胞的相互作用。
Pub Date : 2021-01-10 DOI: 10.15789/1563-0625-iob-2079
D. S. Shlykova, V. Pisarev, A. M. Gaponov, A. Tutelyan
Bacterial extracellular microvesicles (BMV) are formed by nonpathogenic, pathogenic and opportunistic bacteria. BMV are spherical bilayer-membrane organelles containing different cargoes: lipopolysaccharides, pathogen associated molecular patterns (PUMP), DNA, RNA, signal molecules, proteins, antibiotic resistance factors, virulence factors, toxins providing various immune response options and conducive to the survival and pathogen dissemination in the human body. BMVs secretion play an important role in the ability of microorganisms to cause various diseases. BMV are involved in biofilms formation, help bacteria to obtain nutrition in a nutrient-poor conditions, to evade the host's immune response, provide communication and surviving in a stressful environment during infection inside the host. The heterogeneity of the biogenesis mechanisms causes differences in the BMV and their characteristics including virulence rate. BMVs host cells entering is mediated by several mechanisms and helps to activate innate and adaptive immune reactions. This review focuses on interaction study of BMV with various eukaryotic cells types including neutrophils, dendritic cells, macrophages, epithelial, endothelial cells. This interaction depends on bacteria species, type of target cell and number of vesicles and can lead to different responses: non-immunogenic, pro-inflammatory, cytotoxic. Subcellular and molecular mechanisms related to the involvement of extracellular microvesicles in host's immune response modulation are presented. Stimulation of immune response is provided by increased secretion of proinflammatory cytokines and chemokines. In some cases BMV use mechanisms to evade immune surveillance: anti-inflammatory cytokines secretion, alterations of phagocytosis and chemotaxis of macrophages, increasing the proteolytic cleavage of CD14 on the macrophage surface, alterations of antigen-presenting function of dendritic cells, T-cell proliferation suppression, reducing the pro-inflammatory cytokines secretion, evasion of host-immune cells direct interactions, destruction of neutrophilic traps. These features allow bacterial cells to survive in the human body, increase their invasive potential, and reduce the excessive inflammatory reactions leading to death of the pathogen itself and life-threatening damage of tissues and organs of the host. Further studies of these mechanisms will improve existing therapeutic approaches to the infectious diseases treatment.
细菌细胞外微泡(BMV)由非致病性、致病性和机会性细菌形成。BMV是一种球形的双层膜细胞器,含有不同的货物:脂多糖、病原体相关分子模式(pathogen associated molecular patterns, PUMP)、DNA、RNA、信号分子、蛋白质、抗生素耐药因子、毒力因子、毒素,提供各种免疫反应选择,有利于病原体在人体内的生存和传播。bmv的分泌在微生物引起各种疾病的能力中起着重要作用。BMV参与生物膜的形成,帮助细菌在营养不良的条件下获得营养,逃避宿主的免疫反应,在宿主感染期间提供通讯和在紧张环境中生存。生物发生机制的异质性导致BMV及其毒力率等特征存在差异。bmv宿主细胞的进入是由多种机制介导的,并有助于激活先天和适应性免疫反应。本文综述了BMV与中性粒细胞、树突状细胞、巨噬细胞、上皮细胞、内皮细胞等真核细胞相互作用的研究进展。这种相互作用取决于细菌种类、靶细胞类型和囊泡数量,并可导致不同的反应:非免疫原性、促炎性、细胞毒性。介绍了细胞外微泡参与宿主免疫应答调节的亚细胞和分子机制。刺激免疫反应是由促炎细胞因子和趋化因子的分泌增加提供的。在某些情况下,BMV利用机制逃避免疫监视:抗炎细胞因子分泌,巨噬细胞吞噬和趋化性的改变,增加巨噬细胞表面CD14的蛋白水解裂解,树突状细胞抗原呈递功能的改变,t细胞增殖抑制,减少促炎细胞因子分泌,逃避宿主免疫细胞的直接相互作用,破坏嗜中性粒细胞陷阱。这些特点使细菌细胞能够在人体内存活,增加其侵袭潜力,并减少过度的炎症反应,导致病原体本身死亡和对宿主组织和器官的危及生命的损害。对这些机制的进一步研究将改进现有的传染病治疗方法。
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引用次数: 0
Influence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch model 链球菌精氨酸脱亚胺酶对小鼠气囊模型白细胞浸润的影响
Pub Date : 2021-01-10 DOI: 10.15789/1563-0625-IOS-2075
Э. А. Старикова, И. В. Кудрявцев, Л. А. Бурова, А. М. Лебедева, Дж. Т. Мамедова, И. С. Фрейдлин
Numerous pathogens express arginine deiminase, an enzyme that catalyzes the hydrolysis of L-arginine in a chain of biochemical reactions aimed at the synthesis of ATP in bacterial cells. L-arginine is a semi-essential, proteinogenic amino acid that plays an important role in regulating the functions of the immune system cells in mammals. Depletion of L-arginine may cause a weakening of the immune reaction. In order to improve the conditions of dissemination, many pathogens use a strategy of L-arginine depletion in the microenvironment of host cells. Bacterial arginine deiminase can be a pathogenicity factor aimed for dysregulating the processes of inflammation and immune response. In general, the effect of arginine deiminase on immune cells may result into disturbed production of regulatory proinflammatory molecules, such as NO, and related substances, inhibition of activation, migration and differentiation of individual leukocyte subsets. The aim of this study was to investigate the effect of arginine deiminase on the formation of inflammatory infiltrate in murine air pouch model of streptococcal infection. Materials and methods: The study was performed using S. pyogenes M49-16 expressing arginine deiminase and its isogenic mutant S. pyogenes M49-16delArcA with inactivated arginine deiminase gene. The flow cytometry analysis of the inflammatory infiltrate leukocytes subpopulation in mice infected with the original strain of S. pyogenes M49-16 and its isogenic mutant S. pyogenes M49-16delArcA at different periods of infection was performed. It was shown that the inflammation reached its peak 6 hours after streptococcal inoculation, being more pronounced in mice infected with the mutant strain. Тhis finding was affirmed by a simultaneous and more pronounced increase in the absolute numbers of all leukocyte subsets in the focus of inflammation in this group of mice when compared to mice infected with original bacterial strain. Despite the decrease in the absolute number of all leukocyte types in the inflammatory infiltrate in both groups of mice for 24 hours, this trend was more pronounced in the group of mice infected with mutant microbial strain. Comparison of the inflammatory infiltrates developing in mice infected with original versus mutant strains showed that arginine deiminase may be a pathogenicity factor leading to dysregulation of protective immune response, due to impaired migration of white blood cells to the site of infection.
许多病原体表达精氨酸脱亚胺酶,这种酶在一系列生化反应中催化l -精氨酸的水解,目的是在细菌细胞中合成ATP。l -精氨酸是一种半必需的蛋白质生成氨基酸,在哺乳动物免疫系统细胞的功能调节中起着重要作用。l -精氨酸的消耗可能会导致免疫反应的减弱。为了改善传播条件,许多病原体在宿主细胞微环境中使用l -精氨酸耗竭策略。细菌精氨酸脱亚胺酶可能是一种旨在调节炎症和免疫反应过程的致病性因子。一般来说,精氨酸脱亚胺酶对免疫细胞的作用可能导致调节性促炎分子(如NO)及其相关物质的产生受到干扰,抑制单个白细胞亚群的激活、迁移和分化。本研究旨在探讨精氨酸脱亚胺酶对小鼠链球菌感染气袋模型炎性浸润形成的影响。材料和方法:以表达精氨酸脱亚胺酶的S. pyogenes M49-16及其同基因突变体S. pyogenes M49-16delArcA为研究对象,其精氨酸脱亚胺酶基因失活。用流式细胞术分析了原株化脓性链球菌M49-16及其等基因突变株化脓性链球菌M49-16delArcA感染小鼠不同时期的炎性浸润白细胞亚群。结果表明,接种链球菌6小时后炎症达到高峰,在感染突变菌株的小鼠中更为明显。与感染原始菌株的小鼠相比,这组小鼠炎症焦点中所有白细胞亚群的绝对数量同时且更明显地增加,证实了Тhis的发现。尽管两组小鼠炎症浸润中所有白细胞类型的绝对数量在24小时内都有所下降,但这种趋势在感染突变菌株的小鼠组中更为明显。对感染原始菌株和突变菌株的小鼠炎症浸润的比较表明,精氨酸脱亚胺酶可能是导致保护性免疫反应失调的致病因素,原因是白细胞向感染部位的迁移受损。
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引用次数: 0
Features of ophthalmic pathology in autoimmune diseases 自身免疫性疾病的眼部病理特征
Pub Date : 2021-01-10 DOI: 10.15789/1563-0625-foo-2036
M. Lukashenko, N. Basantsova, A. Shishkin
Incidence of the ophthalmic complications in autoimmune diseases is stably increasing over recent years, as well as overall increase in the number of autoimmune pathologies around the world, along with novel diagnostic approaches. According to the WHO estimates, the number of patients with visual impairment is estimated at 285 million people for 2010, causing blindness in 39 million cases. Among autoimmune diseases, diabetes mellitus, sarcoidosis and Behcet’s disease are most often complicated by these conditions. Dry eye syndrome is the most common eye complication associated with these diseases. Our aim was to describe eye complications in type I diabetes, sarcoidosis, and Behcet’s disease, as well as show the importance of research in the area, and to develop common criteria for the care of patients with ophthalmic conditions. The review considers main pathogenetic links, ethnic and genetic factors of ocular pathologies in autoimmune disorders, the main issues of timely diagnosis and the use of various schemes of conservative therapy. The results obtained upon analysis of the literature contain demonstrate the possible autoimmune nature of such eye pathologies, as uveitis and dry eye syndrome in diseases such as type 1 diabetes mellitus, sarcoidosis, and Behcet’s disease. Despite the ongoing research, there are many unresolved issues in the study of pathogenesis, as well as in therapeutic strategy. Therefore, the treatment of autoimmune eye diseases is a difficult task today, including treatment of the underlying disease, and local therapy of the visual organ. Since the primary immunopathology in the mentioned autoimmune diseases requires further studies, it is not possible to accurately predict the course of eye disease, possible complications and outcomes at the present time. Currently, there is only scarce information for creating uniform criteria for the treatment of uveitis and dry eye syndrome in autoimmune diseases. Their further development can contribute to establishment of the principles of medical care, in order to improve efficiency of treatment and quality of life in the patients. Further research and accumulation of data in the field are needed.
近年来,自身免疫性疾病的眼科并发症发生率稳步上升,同时全球自身免疫性疾病的数量也在不断增加,新的诊断方法也在不断涌现。据世卫组织估计,2010年视力障碍患者人数估计为2.85亿人,造成3900万例失明。在自身免疫性疾病中,糖尿病、结节病和白塞氏病最常并发这些疾病。干眼综合征是与这些疾病相关的最常见的眼部并发症。我们的目的是描述1型糖尿病、结节病和白塞氏病的眼部并发症,并表明该领域研究的重要性,并制定眼科疾病患者护理的共同标准。本文综述了自身免疫性疾病眼部病变的主要发病联系、种族和遗传因素、及时诊断的主要问题以及各种保守治疗方案的使用。通过对文献的分析得出的结果表明,诸如1型糖尿病、结节病和白塞病等疾病的葡萄膜炎和干眼综合征等眼病可能具有自身免疫性。尽管研究正在进行,但在发病机制和治疗策略的研究中仍有许多未解决的问题。因此,自身免疫性眼病的治疗是一项艰巨的任务,包括对潜在疾病的治疗和视觉器官的局部治疗。由于上述自身免疫性疾病的原发免疫病理有待进一步研究,目前尚无法准确预测眼病的病程、可能的并发症和转归。目前,对于自身免疫性疾病中葡萄膜炎和干眼综合征的统一治疗标准,只有很少的信息。它们的进一步发展有助于建立医疗保健原则,以提高治疗效率和患者的生活质量。这一领域需要进一步的研究和数据积累。
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Medical immunology (London, England)
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