固有淋巴细胞研究进展

固有淋巴细胞(innate lymphoid cells,ILC)是一群来源于共同淋巴前体(common lymphoid progenitor,CLP),具有固有类细胞特征的淋巴细胞。ILC由多种细胞亚群构成,主要包含NK细胞、Th2ILC和RORγt+ILC,参与组织构建、修复和再生,维持组织稳态,参与固有免疫应答,抗致病菌、寄生虫感染。本文就各类ILC的表型、功能及其与疾病的关系作一综述。     

ILC 细胞与自身炎症性疾病

固有淋巴细胞(ILCs)是一群参与固有免疫的异质性淋巴细胞,多分布于黏膜屏障部位,接受局部微环境细胞因子的信号后,通过分泌细胞因子及其他介质,发挥早期的免疫监视和免疫调节作用。ILCs细胞多为组织驻留淋巴细胞,参与黏膜免疫的形成,在淋巴细胞的发育、组织损伤的修复及上皮屏障的维持方面发挥重要作用。但由于其数量或功能异常,将参与炎症、自身免疫性疾病、代谢性疾病、哮喘、过敏等多种疾病的发生发展。鉴于不同ILC亚群在免疫监视、组织修复、稳态维持和炎症应答中的重要作用,ILCs细胞有望成为免疫治疗或炎症相关疾病治疗的靶点。本文就ILC细胞亚群的表型、发育和功能特点、ILCs细胞在炎症、组织稳态和修复中的作用、与自身炎症性疾病发生发展的关系及相关治疗策略等新进展做一综述。     

Ι型固有淋巴细胞对慢性乙型肝炎的作用及机制

目的初步探讨固有淋巴细胞(ILCs)亚群如ILC1和ILC2(分别为适应性免疫应答中Th1和Th2的映像)对病原体感染的作用机制。方法收集临床慢性乙肝(CHB)患者和健康对照外周血和肝组织,运用流式细胞术、定量PCR和ELISA方法,检测CHB患者中ILC1和ILC2的频率、Ⅰ型和Ⅱ型转录因子和细胞因子水平,并与CHB患者临床指标进行相关性分析。结果CHB患者总ILCs中,ILC1转录因子T-bet、效应细胞因子IFN-γ、ILC1分化相关信号通路分子IL-12/IL-12R水平均显著升高。升高的ILC1亚群频率与CHB患者肝损伤显著相关,但与替比夫定疗效无明显关联。虽然ILC2相关的转录因子、细胞因子等在CHB中也升高,但升高的幅度均低于ILC1细胞。而且,ILC2细胞活性与HBV拷贝或肝损伤均没有显著关联。结论本研究结果提示了ILC1在CHB病理过程中的潜在促炎作用,以及ILC1及其相关分子可能是CHB诊断、预后甚至治疗的潜在干预靶标。     

固有淋巴细胞与临床疾病

ILC是一组新的淋巴细胞群,主要定位在黏膜组织、皮肤和黏膜相关的淋巴器官中。根据ILC表达和分泌的细胞因子不同,把它们分为NK细胞、ILC1、ILC2、ILC3和淋巴组织诱导物(lymphoid tissue induction, LTi)5个细胞亚群,它们在创伤愈合、炎症性肠病、抗感染免疫和肿瘤的发生、发展中起着重要作用。文章就其发育、调控以及与临床疾病关系的最新研究成果进行综述。     

Treg调控ILC2参与炎症性疾病的研究进展

二型固有淋巴细胞(ILC2)是一类表面缺乏特异性抗原识别受体的固有免疫细胞,可被IL-33、IL-25及胸腺基质淋巴细胞生成素(TSLP)等细胞因子活化而释放二型细胞因子,如IL-5和IL-13,进而发挥抗寄生虫感染作用。研究发现,ILC2的过度激活与哮喘、皮炎等炎症性疾病的发生密切相关,抑制ILC2的活化已成为治疗ILC2诱导疾病的重要策略。调节性T细胞(Treg)是一类重要的具有负向免疫调节功能的CD4⁺T细胞亚群,在改善炎症性疾病的进程中发挥重要作用。近年研究发现,Treg可通过多种方式调控ILC2的活化从而缓解炎症性疾病进程。本综述总结了Treg调控ILC2活化的作用机制及其在不同炎症性疾病中扮演的角色,以期为深入研究炎症性疾病中Treg与ILC2的相互作用和炎症性疾病的治疗提供参考。     

Ⅱ型固有淋巴样细胞和树突状细胞相互作用对Th2分化的影响

<正>近些年,尽管对Th2型免疫反应的相关研究不断深入,但Th2细胞初始分化的过程及机制仍不完全清楚。最近的研究发现一群新的固有免疫细胞,界于固有免疫和获得性免疫之间,被称为固有淋巴样细胞(Innate lymphoid cell,ILCs)[1]。其中,Ⅱ型固有淋巴样细胞(Innate lymphoid cells 2,ILC2s)与Th2细胞功能相似,能快速分泌Th2型细胞因子,在     

Ⅱ型固有淋巴细胞在特应性皮炎中作用机制的研究进展

Ⅱ型固有淋巴细胞(typeⅡinnate lymphoid cell,ILC2)是一种新型的固有淋巴细胞群体,活化后可以分泌大量的Th2型细胞因子IL-5、IL-13,主要介导Ⅱ型免疫应答,在抵御寄生虫感染、呼吸道疾病和组织修复中发挥了重要作用。特应性皮炎(atopic dermatitis,AD)是一种慢性复发性皮肤疾病,急性期病理过程主要表现为Th2细胞所介导的Ⅱ型免疫反应。近来发现,ILC2大量存在于人类皮肤的真皮层中,在AD患者的病损皮肤中数量增加并且呈现激活状态,提示ILC2参与了AD的发生发展过程。本文就ILC2在AD中作用机制的研究进展做一综述。     

人类肝脏NK 细胞与肝脏疾病

肝脏疾病的发生发展与免疫反应密切相关。自然杀伤(NK)细胞是固有免疫系统的重要淋巴细胞,在肝脏内的含量十分丰富。人类肝脏NK细胞与外周循环NK细胞的表型和功能差异较大,含有组织驻留特性的NK细胞亚群。NK细胞在抵御病毒感染与肿瘤免疫监视中发挥重要作用。近来研究表明,慢性肝脏疾病中NK细胞表型发生改变,且功能紊乱,不能有效控制病毒感染和肿瘤发展。本文总结了人类肝脏NK细胞的特性和亚群组成,探讨其与固有淋巴细胞(ILC)之间的联系,以及与肝脏疾病的关系,为肝脏疾病的治疗展现新思路。     

皮肤树突状细胞亚群研究进展

皮肤树突状细胞(DC)作为重要的抗原提呈细胞,在机体免疫应答或自身耐受的发生中扮演着非常重要的角色.皮肤免疫系统中定居着多种DC亚群,主要包括表皮层中的郎格汉斯细胞(LC)与真皮层中的各种真皮DC亚群.健康皮肤中的DC亚群主要有表皮LC、真皮DC(dDC)和浆细胞DC(pDC),dDC又分为Langerin+ dDC及Langerin-dDC等.但在炎症性皮肤,如过敏性皮炎、银屑病等病变皮肤中则存在着炎症性DC亚群.DC由于其复杂的异质性群体,导致了其各亚群的特殊化功能.皮肤DC亚群的特殊化功能,为皮肤性疾病的临床治疗及新型疫苗的研发设计等都提供了良好的新策略.     

Ⅲ型固有淋巴细胞中SIRT6在小鼠结肠炎中作用的初探

肠道组织高表达表观遗传调控因子沉默信息调节因子(silent information regulator 6, SIRT6),在UC患者及动物模型的结肠组织中,SIRT6的表达水平显著下调。关于SIRT6在调控肠道免疫平衡中的作用尚不清楚。新近发现的Ⅲ型固有淋巴细胞(group 3 innate lymphoid cell, ILC3)主要分布于肠道,对维持肠道免疫稳态非常重要。为探讨ILC3中SIRT6在结肠炎发生发展中的作用,应用FCM检测小鼠肠道组织中固有淋巴细胞(innate lymphoid cell, ILC)亚群比例,FACS分选ILC,荧光定量PCR检测Sirt6表达。结果发现,Sirt6在ILC3中有较高的表达丰度。运用Cre-loxp系统建立ILC3条件性敲除Sirt6小鼠模型,观察基础状态以及葡聚糖硫酸钠(dextran sulfate sodium salt, DSS)诱导性肠炎模型中小鼠的表型变化。结果显示,Sirt6在ILC3中缺失并不影响基础状态下小鼠的生长发育和肠道结构,但能显著提高小鼠对DSS诱导性结肠炎的抵抗能力。以上结果提示SIRT6通过调控ILC3影响肠炎的发生发展过程。     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.