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Advances in innate immune memory of macrophages 巨噬细胞先天免疫记忆研究进展
Pub Date : 2022-06-28 DOI: 10.37349/ei.2022.00060
S. Khan, M. U. Khan
Immunity is usually classified into two categories: innate immunity and adaptive immunity, distinguished by the process and characteristics of the immunological impact. It was widely assumed that only adaptive immunity possessed memory features; however, current research has revealed that innate immunity, like adaptive immunity, possesses memory properties as well. “Trained immunity”, also known as “innate immune memory”, is a phenomenon that occurs when the immune system’s innate cells are stimulated and then undergo epigenetic reprogramming and metabolic alterations. When it comes to innate immunity, macrophages are essential since they have immunological memory capabilities and play a significant role in the body’s immunity. The concept of innate immune memory expands the definition of immunological memory and offers a broader view of immune response research. This article reviews the properties, mechanism, and significance of macrophage innate immune memory in disease.
免疫通常分为两类:先天免疫和适应性免疫,其区别在于免疫影响的过程和特征。人们普遍认为,只有适应性免疫才具有记忆特征;然而,目前的研究表明,先天免疫和适应性免疫一样,也具有记忆特性。“训练免疫”,也称为“先天免疫记忆”,是一种当免疫系统的先天细胞受到刺激,然后经历表观遗传重编程和代谢改变时发生的现象。当涉及到先天免疫时,巨噬细胞是必不可少的,因为它们具有免疫记忆能力,并在身体免疫中发挥重要作用。先天免疫记忆的概念扩展了免疫记忆的定义,并为免疫反应研究提供了更广阔的视野。本文综述了巨噬细胞先天免疫记忆的性质、机制及其在疾病中的意义。
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引用次数: 2
Cytokines and pregnancy complications: modulation for prevention and treatment 细胞因子与妊娠并发症的防治
Pub Date : 2022-06-27 DOI: 10.37349/ei.2022.00059
R. Raghupathy
“There is many a slip twist the cup and the lip” is a proverb that dates back to the 3rd century. This proverb comes to mind while writing a review on pregnancy loss; so many complications can occur between fertilization and development of the embryo through the long period of gestation until successful delivery of the baby. These include failure of implantation of the embryo, spontaneous miscarriage in the first trimester, pre-eclampsia in the second trimester, premature rupture of fetal membranes, pre-term labour, and pre-term delivery. The maternal immune system which does a phenomenal job of protecting the host from a daunting variety of infections, sometimes also mounts adverse reactions that complicate pregnancy and endanger the fetus. Maternal immune reactions that can adversely affect pregnancy have been shown to be mediated by lymphocytes, macrophages and natural killer cells, and by cytokines secreted by these cellular effectors. This review summarizes the deleterious effects of cytokines leading to recurrent spontaneous miscarriage, pre-eclampsia and pre-term delivery, which are the major complications of pregnancy. It then goes on to discuss the potential use of progesterone and dydrogesterone, an orally-administered progestogen, as immunomodulatory molecules that can be considered for the prevention and/or treatment of these complications.
“杯子和嘴唇之间有很多失误”是一句可以追溯到3世纪的谚语。这句谚语是在写一篇关于流产的评论时想到的;从受精到胚胎发育,在漫长的妊娠期直到成功分娩,都会出现许多并发症。其中包括胚胎植入失败、妊娠早期自然流产、妊娠中期先兆子痫、胎膜早破、早产和早产。母体免疫系统在保护宿主免受各种令人生畏的感染方面发挥了非凡的作用,有时还会产生不良反应,使妊娠复杂化并危及胎儿。可能对妊娠产生不利影响的母体免疫反应已被证明是由淋巴细胞、巨噬细胞和自然杀伤细胞以及这些细胞效应物分泌的细胞因子介导的。本文综述了细胞因子导致复发性自然流产、先兆子痫和早产的有害影响,这些都是妊娠的主要并发症。然后,它继续讨论孕酮和dydrogesterone(一种口服孕激素)作为免疫调节分子的潜在用途,可以考虑用于预防和/或治疗这些并发症。
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引用次数: 1
Polycystic ovary syndrome and immune deregulation: what do hormones want to say? 多囊卵巢综合征与免疫失调:激素想说什么?
Pub Date : 2022-06-27 DOI: 10.37349/ei.2022.00058
Betcy Susan Johnson, M. Laloraya
Polycystic ovary syndrome (PCOS) is one of the most frequently observed endocrinopathies among women of reproductive age that redound to subfertility. The specific etiology of this heterogenic syndrome remains ambiguous. Metabolic complications, hormonal imbalance, deregulation in the immune system and their interrelationship make PCOS more complex. Hyperandrogenism and chronic low-grade inflammation modulate each other and enhance the self-perpetuation of PCOS. Even though there are many literature studies on PCOS and immune deregulation, this review focuses on the endocrine-immune nexus and how the altered endocrine system is embroiled in the immunopathology of PCOS.
多囊卵巢综合征(PCOS)是育龄妇女中最常见的内分泌疾病之一,会导致生育能力低下。这种异质性综合征的具体病因尚不明确。代谢并发症、激素失衡、免疫系统失调及其相互关系使多囊卵巢综合征更加复杂。雄激素过度和慢性低度炎症相互调节,增强多囊卵巢综合征的自我延续。尽管有许多关于多囊卵巢综合征和免疫失调的文献研究,但这篇综述的重点是内分泌-免疫关系,以及改变的内分泌系统如何参与多囊卵巢综合症的免疫病理学。
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引用次数: 0
A multispectral immunohistochemistry panel to investigate γδ T cells and butyrophilin molecules in the tumour microenvironment 肿瘤微环境中γδ T细胞和嗜丁酸蛋白分子的多光谱免疫组化研究
Pub Date : 2022-06-16 DOI: 10.37349/ei.2022.00057
Jessica da Gama Duarte, Luke T. Quigley, Elnaz Tavancheh, Simone Ostrouska, A. Behren
Conventional immunohistochemistry methods though once fundamental for the individual staining of cell markers, have now been superseded by multispectral immunohistochemistry (mIHC). mIHC enables simultaneous detection of multiple cell markers in situ using single formalin-fixed paraffin-embedded (FFPE) tissue sections. In addition to conserving patient tissue specimens, the ability to visualise more than one marker on individual cells allows for further refining of cell phenotypes, and provides insight into cell-to-cell interactions and spatial arrangements across single tissue sections. Here, a comprehensive protocol is described for the in situ interrogation of γδ T cells and phosphoantigen-presenting butyrophilin (BTN) molecules (BTN2A1 and BTN3A1) in human FFPE tissue using Opal™ tyramide signal amplification (TSA)-based mIHC. It is demonstrated that an effectively optimised Opal™-TSA 7-marker [CD3, Pan-γδ T cell receptor (TCR), granzyme B, BTN2A1, BTN3A1, tumour marker, 4’,6-diamidino-2-phenylindole (DAPI)] mIHC panel can be used to define the presence, localisation, and activation status of γδ T cells and the BTN2A1 and BTN3A1 ligands.
传统的免疫组织化学方法虽然曾经是细胞标记物单独染色的基础,但现在已经被多光谱免疫组织化学(mIHC)所取代。使用单个福尔马林固定石蜡包埋(FFPE)组织切片,mIHC能够同时检测多个细胞标记物。除了保存患者组织标本外,在单个细胞上可视化多个标记的能力允许进一步完善细胞表型,并提供洞察细胞间相互作用和跨单个组织切片的空间安排。本文描述了一种基于Opal™酪酰胺信号放大(TSA)的mIHC对人FFPE组织中γδ T细胞和磷酸抗原呈递嗜丁酸蛋白(BTN)分子(BTN2A1和BTN3A1)的原位审讯的综合方案。结果表明,有效优化的Opal™-TSA 7标记物[CD3, Pan-γδ T细胞受体(TCR),颗粒酶B, BTN2A1, BTN3A1,肿瘤标记物,4 ',6-二氨基-2-苯基吲哚(DAPI)] mIHC面板可用于定义γδ T细胞和BTN2A1和BTN3A1配体的存在,定位和激活状态。
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引用次数: 0
Inviting regulatory T cells to pregnant endometrium: friends or foes in adverse pregnancy outcomes? 诱导调节性T细胞进入妊娠子宫内膜:不良妊娠结局的朋友还是敌人?
Pub Date : 2022-06-13 DOI: 10.37349/ei.2022.00056
S. Cheng, Zhengke Wang, Surendra Sharma
Among decidual immune cells, regulatory T cells (Tregs) have been unanimously recognized as central contributors to tolerance and maintenance of healthy pregnancy. Numerical and functional downregulation of Tregs or disturbed interaction of Tregs with trophoblasts and other immune cells have been linked to early pregnancy loss such as idiopathic infertility and miscarriage and later-onset adverse pregnancy outcomes including preeclampsia. This review focuses on the mechanisms for regulating the generation, expansion, and function of Tregs, the roles of Tregs in maintaining maternal immune tolerance through crosstalk with trophoblasts and other decidual regulatory immune cells, and how Tregs may play foes to pregnancy and contribute to the programming of pregnancy-related complications. Therapeutic options for implantation failure and adverse pregnancy outcomes are now part of the emerging significance of Tregs in pregnancy tolerance and maintenance.
在个体免疫细胞中,调节性T细胞(Tregs)被一致认为是耐受和维持健康妊娠的核心贡献者。Tregs的数量和功能下调或Tregs与滋养细胞和其他免疫细胞的相互作用紊乱与早期妊娠丢失(如特发性不孕症和流产)以及迟发性不良妊娠结局(包括先兆子痫)有关。本文综述了Tregs的产生、扩增和功能调控机制,Tregs通过与滋养细胞和其他个体调节性免疫细胞的串扰在维持母体免疫耐受中的作用,以及Tregs如何成为妊娠的敌人并参与妊娠相关并发症的编程。植入失败和不良妊娠结局的治疗选择现在是Tregs在妊娠耐受性和维持中的新意义的一部分。
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引用次数: 0
The influence of reproductive hormones on systemic lupus erythematosus 生殖激素对系统性红斑狼疮的影响
Pub Date : 2022-06-07 DOI: 10.37349/ei.2022.00055
R. Sachdeva, R. Pal
Humans are afflicted by a wide spectrum of autoimmune disorders, ranging from those affecting just one or a few organs to those associated with more systemic effects. In most instances, the etiology of such disorders remains unknown; a consequence of this lack of knowledge is a lack of specific treatment options. Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disorder; pathology is believed to be antibody-mediated, and multiple organs are targeted. Periods of disease “flares” are often followed by long periods of remission. The fact that SLE is more commonly observed in females, and also that it more particularly manifests in females in the reproductive age group, has quite naturally drawn attention to the potential roles that hormones play in disease onset and progression. This review attempts to shed light on the influences that key hormones might have on disease indicators and pathology. Databases (Google Scholar, PubMed) were searched for the following keywords (sometimes in certain combinations), in conjunction with the term “lupus” or “SLE”: autoantibodies, recurrent abortion, polycystic ovarian syndrome (PCOS), preeclampsia, pre-term delivery, estrogens, progesterone, androgens, prolactin, leptin, human chorionic gonadotropin (hCG). Cited publications included both research articles and reviews.
人类受到广泛的自身免疫性疾病的折磨,从只影响一个或几个器官的疾病到与更系统性影响相关的疾病。在大多数情况下,这种疾病的病因仍然未知;这种缺乏知识的后果是缺乏具体的治疗选择。系统性红斑狼疮(SLE)是典型的系统性自身免疫性疾病;病理学被认为是抗体介导的,并且多个器官是靶向的。疾病“发作”后往往会有很长一段时间的缓解期。SLE在女性中更常见,而且在育龄女性中更为明显,这一事实很自然地引起了人们对激素在疾病发作和进展中发挥的潜在作用的关注。这篇综述试图阐明关键激素可能对疾病指标和病理学产生的影响。在数据库(Google Scholar,PubMed)中搜索以下关键词(有时是某些组合),并结合术语“狼疮”或“SLE”:自身抗体、复发性流产、多囊卵巢综合征(PCOS)、先兆子痫、早产、雌激素、孕酮、雄激素、泌乳素、瘦素、人绒毛膜促性腺激素(hCG)。引用的出版物包括研究文章和评论。
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引用次数: 0
Sensing of viral lung infections by cGAS-STING cGAS STING检测病毒性肺部感染
Pub Date : 2022-05-30 DOI: 10.37349/ei.2022.00052
L. Fang, M. Roth
Lower respiratory tract infections caused over 4 million deaths per year worldwide, especially in low-income countries. Viral respiratory infections often occur as rapidly spreading seasonal endemic or epidemic, and sometimes due to new respiratory viruses including corona viruses. The first level of host defense against viral infection is based on the innate immune system and intracellular killing mechanisms. The latter is activated by the release of viral DNA or RNA into the cytosol of the infected cells during the initial phase of virus replication. Viral DNA and RNA are recognized by the cyclic guanosine monophosphate (cGMP)-adenosine monophosphate (AMP) synthase (cGAS)–stimulator of interferon (IFN) genes (STING) sensing pathway, leading to the activation of type-I and -III IFN synthesis, with the aim to limit viral replication. However, the efficacy of the cGAS-STING sensing mechanism seems to vary with different viruses, and therefore, so is the efficacy of the host defense mechanism. Viral DNA can be sensed by different proteins including DNA-dependent activator of IFN regulating factor (DAI), cGAS, and toll-like receptor-9 (TLR-9). Viral RNA is recognized by retinoid acid-inducible gene 1 (RIG-1), TLR-7 and TLR-8. The question if cGAS also recognizes viral RNA remains unclear. The activation of IFN synthesis by cGAS is initiated by the recognition of purines and pyrimidines and their enzymatic conversion into cGMP and cyclic AMP (cAMP), followed by the activation of STING. In addition, it is indicated that several viruses can evade the cGAS-STING signaling and escape the host defense. This review aims to summarize the role of cGAS-STING as a host defense mechanism against viral respiratory tract infections.
下呼吸道感染每年在全球造成400多万人死亡,尤其是在低收入国家。病毒性呼吸道感染通常作为快速传播的季节性地方病或流行病发生,有时是由包括冠状病毒在内的新型呼吸道病毒引起的。宿主对病毒感染的第一级防御是基于先天免疫系统和细胞内杀伤机制。后者在病毒复制的初始阶段通过将病毒DNA或RNA释放到受感染细胞的胞质溶胶中而被激活。病毒DNA和RNA被环鸟苷单磷酸(cGMP)-腺苷单磷酸(AMP)合酶(cGAS)-干扰素(IFN)基因刺激因子(STING)传感通路识别,导致I型和III型IFN合成的激活,目的是限制病毒复制。然而,cGAS-STING传感机制的功效似乎因不同的病毒而异,因此,宿主防御机制的功效也是如此。病毒DNA可以被不同的蛋白质感知,包括DNA依赖性IFN调节因子激活剂(DAI)、cGAS和toll样受体9(TLR-9)。病毒RNA被视黄酸诱导基因1(RIG-1)、TLR-7和TLR-8识别。cGAS是否也能识别病毒RNA的问题尚不清楚。cGAS对IFN合成的激活是由嘌呤和嘧啶的识别及其酶促转化为cGMP和环AMP(cAMP)引发的,然后是STING的激活。此外,研究表明,几种病毒可以逃避cGAS-STING信号并逃避宿主的防御。本综述旨在总结cGAS-STING作为宿主防御病毒性呼吸道感染机制的作用。
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引用次数: 1
Janus face of sepsis: a viewpoint Janus面对败血症:一个观点
Pub Date : 2022-05-24 DOI: 10.37349/ei.2022.00051
M. Bauer, R. Wetzker
Treatment of sepsis currently relies on eliminating the causal pathogen and supportive care, whereas almost no approaches to interfere with the defining event of a “dysregulated host response” are available. This review points to the striking correlation of two phenotypes of sepsis etiopathology with the concept of bipartite response patterns of higher organisms to microbial attacks. According to this concept, the phenotypes of sepsis can be interpreted as either resistance or tolerance responses to infection that got out of hand. This concept might allow focusing sepsis research and related patient studies on key conundrums of current sepsis research: how do resistance responses result in immunopathology and how can tolerance lead to systemic immunosuppression or even immunoparalysis? The heuristic vigor of these questions might inspire experimental efforts and clinical studies and ultimately advance the therapeutic armamentarium for sepsis care.
脓毒症的治疗目前依赖于消除致病病原体和支持性护理,而几乎没有任何方法可以干扰“宿主反应失调”的定义事件。这篇综述指出两种表型的脓毒症病因病理学的显著相关性与高等生物对微生物攻击的两部分反应模式的概念。根据这一概念,败血症的表型可以解释为对感染失控的耐药性或耐受性反应。这一概念可能使脓毒症研究和相关患者研究聚焦于当前脓毒症研究的关键难题:耐药反应如何导致免疫病理,耐受性如何导致全身免疫抑制甚至免疫瘫痪?这些问题的启发式活力可能会激发实验努力和临床研究,并最终推进败血症护理的治疗手段。
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引用次数: 0
Therapeutic and prophylactic applications of self-replicating RNA viruses 自我复制RNA病毒的治疗和预防应用
Pub Date : 2022-05-18 DOI: 10.37349/ei.2022.00050
K. Lundstrom
Self-replicating RNA viruses have been commonly used for preventive and therapeutic interventions in the fields of infectious diseases and cancers. Both RNA viruses with single-stranded RNA genomes of positive and negative polarity have been utilized. Expression of viral surface proteins from self-replicating RNA virus vectors has elicited strong immune responses and provided protection against challenges with lethal doses of pathogens in various animal models using recombinant viral particles, RNA replicons, or plasmid-based replicon vectors. Similarly, immunization with self-replicating RNA virus vectors expressing tumor antigens has induced tumor-specific antibody (Ab) responses, inhibited tumor growth, eradicated tumors, and protected immunized animals against tumor challenges. Clinical trials have demonstrated good safety and tolerance of self-replicating RNA viruses. Although the number of clinical trials is low, robust immune responses and protection against challenges with pathogens and tumor cells have been achieved. The Ervebo vaccine against Ebola virus disease has been approved by both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).
自复制RNA病毒通常用于传染病和癌症领域的预防和治疗干预。具有正极性和负极性单链RNA基因组的两种RNA病毒都已被利用。在使用重组病毒颗粒、RNA复制子或基于质粒的复制子载体的各种动物模型中,自复制RNA病毒载体的病毒表面蛋白的表达引发了强烈的免疫反应,并提供了对抗致命剂量病原体挑战的保护。类似地,用表达肿瘤抗原的自复制RNA病毒载体免疫诱导了肿瘤特异性抗体(Ab)反应,抑制了肿瘤生长,根除了肿瘤,并保护免疫动物免受肿瘤挑战。临床试验表明,自复制RNA病毒具有良好的安全性和耐受性。尽管临床试验的数量很少,但已经实现了强大的免疫反应和对病原体和肿瘤细胞挑战的保护。针对埃博拉病毒疾病的Ervebo疫苗已获得欧洲药品管理局(EMA)和美国食品药品监督管理局(FDA)的批准。
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引用次数: 1
SARS-CoV-2: overview of immune response, insights into vaccine platforms and their challenges 严重急性呼吸系统综合征冠状病毒2型:免疫反应概述、对疫苗平台的见解及其挑战
Pub Date : 2022-05-16 DOI: 10.37349/ei.2022.00049
B. Omar, Arpana Singh, Vanya Singh, Ashish Kothari, Manju O. Pai
The crown-like shaped viruses known as coronaviruses which were first reported in the 1960’s have caused three epidemics in the past two decades namely, coronavirus disease-19 (COVID-19), severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). SARS coronavirus 2 (SARS-CoV-2) was first reported in the latter half of December in Wuhan, a city of China, with people affected by deadly pneumonia with unknown etiology. Since then, the world has experienced two phases of virus spread with different symptoms and disease severity. This review embarks on the journey to investigate candidate molecules of this virus which can and are being investigated for various vaccine formulations and to discuss immunity developed against this virus.
20世纪60年代首次报道的冠状病毒,即冠状病毒,在过去20年中引起了三种流行病,即冠状病毒病-19(新冠肺炎)、严重急性呼吸综合征(SARS)和中东呼吸综合征。SARS冠状病毒2型(严重急性呼吸系统综合征冠状病毒2型)于12月下旬在中国武汉首次报告,患者感染了病因不明的致命肺炎。从那时起,世界经历了病毒传播的两个阶段,症状和疾病严重程度各不相同。这篇综述开始了研究这种病毒的候选分子的旅程,这些分子可以并且正在被研究用于各种疫苗配方,并讨论针对这种病毒产生的免疫力。
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引用次数: 0
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Exploration of immunology
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