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A scalable, spin-free approach to generate enhanced induced pluripotent stem cell–derived natural killer cells for cancer immunotherapy 一种可扩展的无自旋方法,可生成用于癌症免疫疗法的增强型诱导多能干细胞衍生自然杀伤细胞。
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-09-13 DOI: 10.1111/imcb.12820
Gustavo R Rossi, Jane Sun, Cheng-Yu Lin, Joshua KM Wong, Louisa Alim, Pui Yeng Lam, Kiarash Khosrotehrani, Ernst Wolvetang, Seth W Cheetham, Emily B Derrick, Akwasi Amoako, Christoph Lehner, Andrew J Brooks, Paul A Beavis, Fernando Souza-Fonseca-Guimaraes

Natural killer (NK) cells play a vital role in innate immunity and show great promise in cancer immunotherapy. Traditional sources of NK cells, such as the peripheral blood, are limited by availability and donor variability. In addition, in vitro expansion can lead to functional exhaustion and gene editing challenges. This study aimed to harness induced pluripotent stem cell (iPSC) technology to provide a consistent and scalable source of NK cells, overcoming the limitations of traditional sources and enhancing the potential for cancer immunotherapy applications. We developed human placental–derived iPSC lines using reprogramming techniques. Subsequently, an optimized two-step differentiation protocol was introduced to generate high-purity NK cells. Initially, iPSCs were differentiated into hematopoietic-like stem cells using spin-free embryoid bodies (EBs). Subsequently, the EBs were transferred to ultra-low attachment plates to induce NK cell differentiation. iPSC-derived NK (iNK) cells expressed common NK cell markers (NKp46, NKp30, NKp44, CD16 and eomesodermin) at both RNA and protein levels. iNK cells demonstrated significant resilience to cryopreservation and exhibited enhanced cytotoxicity. The incorporation of a chimeric antigen receptor (CAR) construct further augmented their cytotoxic potential. This study exemplifies the feasibility of generating iNK cells with high purity and enhanced functional capabilities, their improved resilience to cryopreservation and the potential to have augmented cytotoxicity through CAR expression. Our findings offer a promising pathway for the development of potential cellular immunotherapies, highlighting the critical role of iPSC technology in overcoming challenges associated with traditional NK cell sources.

自然杀伤(NK)细胞在先天性免疫中发挥着重要作用,在癌症免疫疗法中大有可为。传统的 NK 细胞来源(如外周血)受到可用性和供体变异性的限制。此外,体外扩增可能导致功能耗竭和基因编辑难题。本研究旨在利用诱导多能干细胞(iPSC)技术,提供稳定、可扩展的NK细胞来源,克服传统来源的局限性,提高癌症免疫疗法的应用潜力。我们利用重编程技术开发了人类胎盘iPSC系。随后,我们引入了一个优化的两步分化方案来生成高纯度的NK细胞。首先,利用无旋胚状体(EB)将iPSC分化成造血类干细胞。iPSC 衍生的 NK(iNK)细胞在 RNA 和蛋白质水平上都表达常见的 NK 细胞标记(NKp46、NKp30、NKp44、CD16 和 eomesodermin)。嵌合抗原受体(CAR)构建体的加入进一步增强了它们的细胞毒性潜力。这项研究证明了生成具有高纯度和增强功能的 iNK 细胞的可行性,它们对冷冻保存的适应性得到了改善,并有可能通过 CAR 表达增强细胞毒性。我们的研究结果为开发潜在的细胞免疫疗法提供了一条前景广阔的途径,凸显了 iPSC 技术在克服传统 NK 细胞来源相关挑战方面的关键作用。
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引用次数: 0
The expanding universe of type I regulatory T cell biology: a new role in cancer immunotherapy 不断扩展的 I 型调节性 T 细胞生物学:癌症免疫疗法中的新角色。
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-09-11 DOI: 10.1111/imcb.12822
Jason F Nideffer, Prasanna Jagannathan

In this article, we discuss new findings which suggest that type I regulatory T (Tr1) cells can interfere with cancer vaccine efficacy in mice by exerting strong regulatory control over antitumor immune responses.

本文讨论的新发现表明,I型调节性T细胞(Tr1)可通过对抗肿瘤免疫反应施加强有力的调节控制,干扰小鼠体内癌症疫苗的疗效。
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引用次数: 0
Improving the Quality of Adolescent and Youth-Friendly Health Services Through Integrated Supportive Supervision in Four Nigerian States. 通过在尼日利亚四个州开展综合支持性监督,提高青少年健康服务的质量。
IF 2.5 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-05-21 DOI: 10.9745/GHSP-D-22-00169
Dorcas Akila, Akinola Oluwasegun, Krishna Bose, Olukunle Omotoso, Adewale Adefila, Lisa Mwaikambo

Background: Although the unique sexual and reproductive health needs of adolescents and youth (AY) are widely recognized, the challenge remains how to integrate adolescent- and youth-friendly health services (AYFHS) effectively within a systems-based approach that is both feasible and scalable. This article provides preliminary evidence from 4 Nigerian states that sought to overcome this challenge by implementing capacity-strengthening approaches centered around a shortened quality assurance (QA) tool that has become part of the state health system's routine supportive supervision process and follow-up quality improvement (QI) activities.

Methods: A shortened QA tool was administered to assess and track the performance of 130 high-volume health facilities across 5 domains to serve its AY population with quality contraceptive services. Facility-based providers (N=198) received training on adolescent and youth sexual and reproductive health, AYFHS, and long-acting reversible contraceptive methods. To corroborate checklist findings, we conducted exit interviews with 754 clients (aged 15-24 years) who accessed contraceptive services from the facilities that met the World Health Organization's minimum standards for quality AYFHS.

Results: In the 4 states, the QA tool was applied at baseline and 2 rounds, accompanied by QI capacity strengthening after each round. At baseline, only 12% of the 130 facilities in the 4 states scored met the minimum quality standards for AYFHS. After 2 rounds, 88% of the facilities met the minimum standards. AY client volume increased over this same period. All 4 states showed great improvements; however, the achievements varied by state. The exit interview feedback supported client satisfaction with the services provided to AY.

Conclusion: Integrating QA followed by QI within Nigeria's family planning supportive supervision system is not only feasible but also impacts the quality of AYFHS and contraceptive uptake by clients aged 15-24 years.

背景:尽管青少年和青年(AY)独特的性健康和生殖健康需求已得到广泛认可,但如何将青少年和青年友好型健康服务(AYFHS)有效地整合到以系统为基础的方法中,使其既可行又可扩展,仍然是一项挑战。本文提供了尼日利亚 4 个州为克服这一挑战而采取的初步措施,这些州实施了以简短质量保证(QA)工具为中心的能力强化方法,该工具已成为州卫生系统常规支持性监督程序和后续质量改进(QI)活动的一部分:方法:采用简化的质量保证工具来评估和跟踪 130 家高服务量医疗机构在 5 个领域中的表现,以便为其青壮年人口提供优质的避孕服务。医疗机构的服务提供者(198 人)接受了有关青少年性健康和生殖健康、AYFHS 和长效可逆避孕方法的培训。为了证实核对表的结果,我们对 754 名客户(15-24 岁)进行了离职访谈,他们都曾在符合世界卫生组织青少年生殖健康优质服务最低标准的机构接受过避孕服务:在这 4 个州,质量保证工具在基线阶段和两轮阶段都得到了应用,并在每轮阶段后加强了质量保证能力。在基线阶段,4 个州 130 家医疗机构中只有 12% 的医疗机构达到了青少年家庭保健服务的最低质量标准。两轮评估后,88%的机构达到了最低标准。在同一时期,"青少年家庭健康服务 "的客户量也有所增加。所有 4 个州都取得了巨大进步,但各州取得的成绩不尽相同。离职访谈反馈支持客户对 AY 服务的满意度:在尼日利亚的计划生育支持性监督系统中整合质量保证和质量改进,不仅是可行的,而且还能提高 AYFHS 的质量和 15-24 岁客户的避孕率。
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引用次数: 0
Oxidized thioredoxin 1 places a leash on NLRP1 inflammasome activity 氧化硫氧还蛋白1限制NLRP1炎症小体的活性。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-11-10 DOI: 10.1111/imcb.12710
Jeremy KY Yap, Stefan Emming, Kate Schroder

The biology of the NACHT domain and leucine-rich repeat (NLR) and pyrin domain-containing 1 (NLRP1) inflammasome has perplexed researchers since this inflammasome was first described about two decades ago. The identification of oxidized thioredoxin 1 (TRX1) as a suppressor of NLRP1 recently linked cellular redox homeostasis to NLRP1 inflammasome signaling. Now, Zhang et al. present a molecular structure of TRX1-bound NLRP1 with unprecedented detail. This structure gives key insight into regulatory mechanisms governing NLRP1 activation and offers enormous potential for structure-based anti-inflammatory drug design.

自从大约20年前首次描述这种炎症小体以来,NACHT结构域和富含亮氨酸重复序列(NLR)以及含有pyrin结构域的1(NLRP1)炎症小体的生物学一直困扰着研究人员。氧化硫氧还蛋白1(TRX1)作为NLRP1抑制剂的鉴定最近将细胞氧化还原稳态与NLRP1炎症小体信号传导联系起来。现在,张等人。以前所未有的细节呈现了TRX1结合的NLRP1的分子结构。该结构为NLRP1激活的调控机制提供了关键见解,并为基于结构的抗炎药设计提供了巨大潜力。
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引用次数: 0
Immunology across two islands: understanding the research landscape of Aotearoa (New Zealand) 跨越两个岛屿的免疫学:了解Aotearoa(新西兰)的研究景观。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-11-03 DOI: 10.1111/imcb.12709
Joanna R Kirman, Robert Weinkove, Jessica G Borger

In the unique landscape of immunology research in New Zealand, this article explores the collaborative networks spanning the two main islands, through a conversation with Associate Professor Joanna Kirman and Dr Robert Weinkove. The discussions delve into their dynamic collaborations with countries such as Asia, Australia and the United States, from their laboratories at the University of Otago and the Malaghan Institute of Medical Research, respectively, provides insight into the translational research landscape of New Zealand, and the integration of Māori culture into all aspects of scientific research and clinical practise. Kirman's work in understanding immunological memory in tuberculosis and Weinkove's research in cancer immunotherapies, particularly CAR-T cells, are highlighted. The natural beauty and accessibility of New Zealand supports its research diversity.

在新西兰免疫学研究的独特景观中,本文通过与Joanna Kirman副教授和Robert Weinkove博士的对话,探索了横跨两个主要岛屿的合作网络。讨论深入探讨了他们分别在奥塔哥大学和马拉汉医学研究所的实验室与亚洲、澳大利亚和美国等国家的动态合作,深入了解了新西兰的转化研究前景,将毛利文化融入科学研究和临床实践的各个方面。重点介绍了Kirman在理解结核病免疫记忆方面的工作,以及Weinkove在癌症免疫疗法,特别是CAR-T细胞方面的研究。新西兰的自然美景和可及性支持了其研究的多样性。
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引用次数: 0
100 years of Immunology & Cell Biology 100 免疫学和细胞生物学。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-11-01 DOI: 10.1111/imcb.12707
Adrian Liston
<p>It is a special honor to be penning an editorial to introduce our final issue this year, the 100th years of publication of <i>Immunology & Cell Biology</i>.</p><p>I am hardly alone among Australian and New Zealand immunologists in having a special place in my heart for <i>Immunology & Cell Biology</i>. The journal was founded 100 years ago in Adelaide as the <i>Australian Journal of Experimental Biology and Medical Science</i> but became <i>Immunology & Cell Biology</i> more recently under Ieva Kotlarski in 1987. I first studied immunology at the University of Adelaide in Ieva's last years prior to retirement, although by that time the journal had moved over to Canberra under Chris Parish's leadership. My career followed that of <i>Immunology & Cell Biology</i>, as I moved for my PhD in Chris Goodnow's lab to the John Curtain School of Medical Research, with the Parish lab just down the hallway. <i>ICB</i> was ubiquitous, with all students and staff receiving the monthly issue in their pigeonhole, making it one of the few journals that everyone flicked through the pages of. One of my very first papers found its home in <i>ICB</i>,<span><sup>1</sup></span> in a field on which I am still working today.</p><p>A special moment for me in my early career came through Chris Parish's request for me to review a paper for <i>ICB</i>. Reviewing papers with my supervisor was a common enough request, but a request direct to me, as a PhD student, felt entirely different, it was a moment where I felt that perhaps I was also a professional scientist. I will be forever grateful to Chris for being so inclusive of early career researchers, a theme which I hope to continue for the journal. I later served on the editorial board under Chris, and as Deputy Editors under Gabrielle Belz, at the pivotal point where Gabrielle created the sister journal <i>Clinical & Translational Immunology</i>.<span><sup>2</sup></span> I took a few years out from <i>ICB</i> service, in anticipation of a professional move to Cambridge, but when the opportunity arose to apply for Editor-in-Chief I thought “where better to invest my service time than in the journal that supported my early career.” I rejoined as Deputy Editor under Anne La Flamme, and observed her boundless energy, before taking up the EiC position myself earlier this year.</p><p>What magnificent timing! To be Editor-in-Chief as we enter our 100th year! I must say, I thought I knew <i>ICB</i> well, but my decades of interaction with the journal barely scratched the surface of its history. It wasn't until this year, preparing for our centenary, that I realized how profoundly <i>ICB</i> has shaped immunology, at a personal, national and international level. Early editors are mythical figures in Australian immunology – many current immunologists (including myself) were trained under the CJ Martin Fellowship, named after one of our early Editors-in-Chief, while Derrick Rowley, EiC decades later, founded the
我特别荣幸地为我们今年的最后一期——《免疫学》出版100周年——写一篇社论。细胞生物学。在澳大利亚和新西兰的免疫学家中,免疫学在我心中占有特殊地位的并不只是我一个人。细胞生物学。该杂志100年前在阿德莱德创刊,当时名为《澳大利亚实验生物学和医学科学杂志》,后来更名为《免疫学》。细胞生物学最近在1987年由Ieva Kotlarski教授。在Ieva退休前的最后几年,我在阿德莱德大学(University of Adelaide)学习了免疫学,尽管那时杂志已经搬到了堪培拉,由克里斯·帕里什(Chris Parish)领导。我的职业生涯紧随免疫学之后。细胞生物学,因为我从克里斯·古德诺的实验室搬到约翰·柯德医学院攻读博士学位,教区实验室就在走廊那头。ICB无处不在,所有的学生和教职员工都会在他们的文件夹里收到月刊,这使它成为少数几个人人都会翻阅的期刊之一。我最早的一篇论文是在ICB中找到的,我今天仍在研究这个领域。在我早期的职业生涯中,克里斯·帕里什(Chris Parish)邀请我为ICB审阅一篇论文,这对我来说是一个特殊的时刻。和我的导师一起审阅论文是很常见的要求,但作为一名博士生,直接向我提出的要求感觉完全不同,在那个时刻,我觉得自己也许也是一名专业科学家。我将永远感激克里斯对早期职业研究人员的包容,我希望这一主题能在杂志上继续下去。后来,我在克里斯手下担任编辑委员会成员,并在加布里埃尔·贝尔兹手下担任副编辑,在加布里埃尔创办姊妹期刊《临床》的关键时刻;翻译免疫学2我离开ICB工作了几年,期待着成为剑桥大学的专业人士,但当有机会申请总编辑时,我想“有什么比在支持我早期职业生涯的期刊上投入我的服务时间更好的地方呢?”在今年早些时候我开始担任EiC的职位之前,我重新加入了安妮·拉·弗莱姆(Anne La Flamme)的副主编,并观察到了她无限的活力。多好的时机啊!在我们进入100周年之际担任总编辑!我必须说,我以为我很了解ICB,但我与该杂志几十年的互动仅仅触及了它历史的表面。直到今年,在筹备我们的百年纪念时,我才意识到ICB在个人、国家和国际层面上对免疫学产生了多么深远的影响。早期的编辑是澳大利亚免疫学的神话人物-许多现在的免疫学家(包括我自己)都是在CJ马丁奖学金下接受培训的,该奖学金以我们早期的主编之一命名,而德里克罗利,EiC几十年后,创立了澳大利亚免疫学学会(今天的澳大利亚和新西兰免疫学学会的前身)。至于几十年来在ICB上发表的内容……我可能有偏见,但我认为很少有期刊(如果有的话)对免疫学的基本租户产生如此深刻的影响。从麦克法兰·伯内特(MacFarlane burnett)的克隆选择理论,到弗兰克·芬纳(Frank Fenner4)关于痘免疫的发现(最终以他领导的根除天花运动而告终),从唐·梅特卡夫(Don Metcalf)的菌落形成试验,到肯·肖尔曼(Ken Shortman)的密度梯度离心法,我们的杂志奠定了免疫学的基础。ICB的贡献还不止于此——格斯·诺萨尔关于生发中心形成的研究,凯文·拉弗蒂的“两信号假说”,OT-II转基因小鼠的产生,以及用于淋巴细胞增殖的CFSE方法的发明——都首先发表在ICB上。我对国际清算银行过去100年的贡献只做了皮毛,但幸运的是,我们有一个完整的问题来探讨贡献。我们的头条文章回顾了这100年来的人物和历史,我保证这篇文章读起来会很吸引人。如果你想了解更多关于某个特定时代的信息,我们有关于早期、中期和现代的更详细的文章。如果你想了解更多关于ICB是如何在二战潜艇封锁国际航运的背景下发展起来的,或者马克·米切尔是如何说服NHMRC在定量配给期间资助纸张供应的,看看吧。在这一期中,我们还深入探讨了一些使该杂志发展到今天的关键人物——包括凯文·拉弗蒂、比德·莫里斯、玛格丽特·贝尔德、多拉·卢什和艾伦·威廉·克里普斯。我们还对编辑团队进行了一次精彩的采访,他们使ICB的一切都发生了——对于任何对期刊幕后运作感兴趣的人来说,这是必须的最后,我们将重点关注ICB取得历史成就的几个关键领域——肿瘤免疫学、兽医免疫学和临床免疫学。我希望你们喜欢读这一期《国际商业银行》,就像我们喜欢制作它一样。 Adrian Liston是《免疫学》杂志的主编。细胞生物学。
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引用次数: 0
A Touch of Immunology: improving accessibility to the science of antibodies for people with blindness, low vision and diverse needs 免疫学:为失明、视力低下和各种需求的人提高抗体科学的可及性。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-10-31 DOI: 10.1111/imcb.12708
Jack Polmear, Liam Kealy, Hui Xu, Kim L Good-Jacobson

Immunology for all: Most scientific communication has historically been limited to visual imagery and the written or spoken word, often in the form of dense articles obscured by jargon. Clear communication of science is vital to enable the public to engage with important scientific discoveries and to limit medical distrust. However, scientific communication is often executed in a way which neglects people with blindness, low vision and diverse needs. Our aim for the exhibit at the Monash Sensory Science Exhibition on Autoimmunity 2023 at Monash University was to develop novel, tactile and informative models to help better communicate the scientific principles that underpin autoimmune disease and immunology. As B-cell biologists, we decided to focus our exhibit for this workshop on antibody-mediated autoimmunity. Antibodies are key components of the immune system, providing protection against a range of diverse pathogens. However, in the context of autoimmunity, they can also drive pathology.

所有人的免疫学:历史上,大多数科学交流都局限于视觉图像和书面或口头单词,通常以被行话掩盖的密集文章的形式进行。科学的清晰交流对于让公众参与重要的科学发现和限制医学上的不信任至关重要。然而,科学交流往往忽视了盲人、低视力和多样化需求的人。我们在莫纳什大学2023年莫纳什自身免疫感官科学展上展出的目的是开发新颖、触觉和信息丰富的模型,以帮助更好地传达支撑自身免疫疾病和免疫学的科学原理。作为B细胞生物学家,我们决定将此次研讨会的展览重点放在抗体介导的自身免疫上。抗体是免疫系统的关键组成部分,可以抵御各种各样的病原体。然而,在自身免疫的背景下,它们也可以驱动病理学。
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引用次数: 0
Allan William Cripps: a mucosal immunologist and mentor from beginning to end 艾伦·威廉·克里普斯:粘膜免疫学家,从始至终的导师。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-10-27 DOI: 10.1111/imcb.12706
Maree Gleeson, Nicholas P West

Allan Cripps was internationally recognized in the field of mucosal immunology, in particular the relationship between respiratory diseases and mucosal immunization strategies. Allan's career spanned scientific and applied research, commercialization, health education, and evolved into leadership roles in public-health and academic administration. Allan published over 400 papers and mentored over 40 research higher degree candidates. Allan was renowned for his mentorship, that did not end with the awarding of a PhD or Master's degree, but continued across a lifetime of professional engagement. Allan's key contributions to immunology included characterizing the ontogeny of the human mucosal immune system, understanding the impact of respiratory infections and otitis media in children, developing diagnostic technologies and mucosal vaccine strategies, and identifying the roles of the common mucosal immune system in human health. In this biography for the 100th anniversary of the Journal, we follow his journey of discovery and contributions to immunological research.

Allan Cripps在粘膜免疫学领域,特别是呼吸道疾病与粘膜免疫策略之间的关系方面获得了国际认可。艾伦的职业生涯横跨科学和应用研究、商业化、健康教育,并发展成为公共卫生和学术管理领域的领导角色。艾伦发表了400多篇论文,指导了40多名研究生。艾伦以导师制而闻名,导师制并没有以博士或硕士学位的授予而结束,而是持续了他一生的职业生涯。Allan在免疫学方面的主要贡献包括表征人类粘膜免疫系统的个体发育,了解儿童呼吸道感染和中耳炎的影响,开发诊断技术和粘膜疫苗策略,以及确定常见粘膜免疫系统在人类健康中的作用。在这本纪念《华尔街日报》100周年的传记中,我们关注他的发现之旅和对免疫学研究的贡献。
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引用次数: 1
A long and winding road: the history of Immunology & Cell Biology from 1936 to 1987 漫长而曲折的道路:免疫学和细胞生物学的历史从1936年到1987年。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-10-25 DOI: 10.1111/imcb.12704
Judith M Greer

This piece for the 100th year of publication of Immunology & Cell Biology focuses on the contributions of two long-serving Editors-in-Chief, Mark Mitchell (1936–1963) and Derrick Rowley (1963–1987). This was a period of growth and consolidation for the journal, through sometimes challenging and changing times. Some of the notable works published in the journal during this time are also highlighted.

这篇发表于《免疫学与细胞生物学》100周年的文章聚焦于两位长期担任主编的Mark Mitchell(1936-1963)和Derrick Rowley(1963-1987)的贡献。这是该杂志成长和巩固的时期,经历了有时充满挑战和变化的时代。在此期间发表在该杂志上的一些著名作品也被重点介绍。
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引用次数: 1
History of Veterinary Immunology in New Zealand 新西兰兽医免疫学史。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-10-22 DOI: 10.1111/imcb.12705
Bryce M Buddle

Knowledge gained from veterinary immunology has played an important role in the control of microbial and parasitic diseases in New Zealand through the development and use of vaccines and diagnostic tests. In this article celebrating the 100th anniversary of the Journal, I follow the development of important discoveries in veterinary immunology which have led to major advances in the control of animal diseases.

通过开发和使用疫苗和诊断测试,从兽医免疫学中获得的知识在新西兰控制微生物和寄生虫病方面发挥了重要作用。在这篇庆祝《动物免疫学杂志》创刊100周年的文章中,我关注兽医免疫学的重要发现的发展,这些发现导致了动物疾病控制的重大进展。
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引用次数: 1
期刊
Immunology & Cell Biology
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