Anti-viral immune responses in lymph node

淋巴结的抗病毒免疫反应

• 批准号: 8306012
• 负责人: ULRICH H VON ANDRIAN
• 金额: $ 238.65万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306012
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Address; Adenoviruses; Affinity; Anatomy; Animal Model; Animals; Antibodies; Antigen-Presenting Cells; Antigens; Antiviral Agents; B-Cell Activation; B-Lymphocytes; Behavior; Binding; Biological Models; Blood Circulation; Blood Vessels; Blood flow; Body measure procedure; Bone Marrow; CD4 Positive T Lymphocytes; Cell Communication; Cell physiology; Cells; Characteristics; Chronic; Clinical; Collaborations; Complement; Complement 3d Receptors; Complement Receptor; Coupling; Cytotoxic T-Lymphocytes; Data; Dendritic Cells; Deposition; Detection; Development; Disease; Drainage procedure; ERBB2 gene; Effectiveness; Event; Exposure to; Floor; Follicular Dendritic Cells; Functional disorder; Gatekeeping; Generations; Goals; HIV; HIV Antigens; Helper-Inducer T-Lymphocyte; Hematopoietic; Host Defense; Human; Humoral Immunities; Image; Imagery; Immune; Immune response; Immune system; Immunity; Immunization; Immunoglobulin Class Switching; Immunologic Memory; Immunologist; Individual; Infection; Inflammatory; Influenza; Injection of therapeutic agent; Intervention; Investigation; Kinetics; Knowledge; Lead; Learning; Left; Life; Ligands; Liquid substance; Lymph; Lymph Node Subcapsular Sinus; Lymphatic; Lymphatic System; Lymphocyte; Lymphocytic choriomeningitis virus; Mammals; Memory; Memory B-Lymphocyte; Microbe; Mind; Modeling; Molecular; Monoclonal Antibodies; Mouse Strains; Mucous Membrane; Mus; Mutation; Myelogenous; Natural Immunity; Organ; Outcome; Pan Genus; Pathway interactions; Pattern; Peripheral; Phagocytes; Phase; Phenotype; Physiological; Plant Roots; Play; Positioning Attribute; Prevention; Process; Property; Proteins; Reaction; Receptor Signaling; Recording of previous events; Regulation; Relative (related person); Research Personnel; Resistance; Reticular Cell; Role; Route; Series; Simplexvirus; Sinus; Site; Skin; Source; Stem cells; Stream; Streptococcus pneumoniae; Structure of germinal center of lymph node; Structure of subclavian vein; Surface; System; T cell response; T-Lymphocyte; Testing; Thoracic Duct; Time; Tissues; Travel; Vaccines; Vaccinia virus; Vesicular stomatitis Indiana virus; Viral; Viral Antigens; Viral Vaccines; Virion; Virus; Virus Diseases; Work; adaptive immunity; antigen challenge; base; capsule; cell motility; complement pathway; complement system; cytokine; evidence base; exhaust; improved; in vivo; influenzavirus; insight; intravital microscopy; lymph nodes; macrophage; microbial; mouse model; multi-photon; nanoparticle; new therapeutic target; novel therapeutics; particle; pathogen; prevent; programs; prophylactic; receptor; research study; response; stem; tool; vaccine development; virus pathogenesis

DESCRIPTION (provided by applicant): This Program entitled "Anti-viral Immune Responses in Lymph Nodes" seeks to gain a deeper understanding of the induction and regulation of immunological events that are elicited by viral antigens in lymph nodes (LNs). Many viruses and most conventional vaccines enter the body through the skin and travel via lymphatics to draining LNs. These organs are believed to have a critical role in the adaptive immune response to peripheral infections; therefore, understanding the cellular and molecular interactions that occur within LNs will provide insights that may be useful for improved vaccine development. Lymph-borne foreign matter entering LNs is captured and processed by antigen-presenting cells (APCs), which then present this material to B and T cells to elicit effector responses and long-lived immunological memory. The rules that determine how lymph-derived antigenic material is handled in LNs, especially in the context of ongoing infections, and what cells and molecules must interact to elicit a protective immune response (or fail to do so) are poorly understood. Why do some viruses (e.g. VSV in mice) induce a potent, multi-pronged protective immune response that eliminates the pathogen, while others (e.g. influenza) generate only transient protective immunity, and a few (e.g. HIV in humans) establish a chronic presence by continuously subverting and eventually exhausting the host's anti-viral defenses? The mechanisms behind these different outcomes are likely multi-factorial and depend upon differences in the way individual viruses interact with their hosts. To explore the dynamics of these interactions in living animals, all component projects of this Program will employ multi-photon intravital microscopy (MP-IVM) in intact LNs that will be offered in the Intravital Microscopy Core for time-and space-resolved visualization of the innate and adaptive immune response to lymph-borne virions. In Project 1, Dr. von Andrian will explore innate and adaptive immune responses to lymph-borne viral infections using VSV and several other viral pathogens. In Project 2. Drs. Sharpe and Wherry will visualize the effects of the negative costimulatory pathways, PD-1:PD-L1, PD-1:PD-L2 and PDL1 :B7.1 on antiviral immunity to influenza and LCMV. In Project 3. Dr. Carroll will dissect the role of complement and complement receptors in humoral immunity to influenza virus. Finally, in Project 4, Drs. Luster. Mempel and Tager will characterize the cellular dynamics and viral dissemination in HIV-infected lymph nodes of humanized mice. It is hoped that the mechanistic insights gained from these highly interactive and synergistic experiments will lead to new, evidence-based and knowledge-driven development strategies for anti-viral vaccines.

描述（由申请人提供）：该计划标题为“淋巴结中的抗病毒免疫反应”，旨在更深入地了解淋巴结病毒抗原（LNS）引起的免疫事件的诱导和调节。许多病毒和大多数常规疫苗通过皮肤进入人体，并通过淋巴管传播到排水LN。据信这些器官在对周围感染的适应性免疫反应中起关键作用。因此，了解LN中发生的细胞和分子相互作用将提供可能有助于改善疫苗发育的见解。进入LNS的淋巴传播异物被抗原呈递细胞（APC）捕获并处理，然后将此材料呈现给B和T细胞，以引起效应子反应和长期寿命的免疫记忆。确定淋巴衍生的抗原材料在LN中如何处理的规则，尤其是在持续感染的背景下，以及细胞和分子必须相互作用以引起保护性免疫反应（或不这样做）。为什么某些病毒（例如，小鼠中的VSV）引起有效的，多管齐的保护性免疫反应，消除病原体，而另一些病毒（例如，流感）仅产生短暂的保护性免疫，而少数（例如，人类的HIV）（例如，人类的HIV）通过连续颠覆和耗尽了主持人的抗杀伤力来建立持续的持续存在？这些不同结果背后的机制可能是多因素的，并且取决于单个病毒与宿主相互作用的方式的差异。为了探索活动物中这些相互作用的动态，该程序的所有组件项目将在完整的LN中采用多光子内内玻璃体内显微镜（MP-IVM），这些显微镜将在插入式显微镜核心中提供，以实现对淋巴结蛋白病毒体的先天和适应性免疫反应的时间和空间分辨的可视化。在项目1中，冯·安德里安（Von Andrian）博士将使用VSV和其他几种病毒病原体探索对淋巴传播病毒感染的先天和适应性免疫反应。在项目2中。 Sharpe和Wherry将可视化阴性共刺激途径的影响PD-1：PD-L1，PD-1：PD-L2和PDL1和PDL1：B7.1对流感和LCMV的抗病毒免疫。在项目3中。卡洛尔博士将剖析补体和补体受体在对流感病毒的体液免疫中的作用。最后，在项目4中，博士。光泽。 MEMPEL和TAGER将表征人文化小鼠的HIV感染淋巴结中的细胞动力学和病毒传播。希望从这些高度互动和协同的实验中获得的机械见解将导致针对抗病毒疫苗的新的，基于证据和知识驱动的发展策略。

项目成果

Ontogenetic regulation of leukocyte recruitment in mouse yolk sac vessels.

小鼠卵黄囊血管中白细胞募集的个体发育调控。

• DOI: 10.1182/blood-2012-07-447144
• 发表时间: 2013
• 期刊: Blood
• 影响因子: 20.3
• 作者: Sperandio,Markus;Quackenbush,ElizabethJ;Sushkova,Natalia;Altstätter,Johannes;Nussbaum,Claudia;Schmid,Stephan;Pruenster,Monika;Kurz,Angela;Margraf,Andreas;Steppner,Alina;Schweiger,Natalie;Borsig,Lubor;Boros,Ildiko;Krajewski,Nele
• 通讯作者: Krajewski,Nele

Complement and humoral immunity.

• DOI: 10.1016/j.vaccine.2008.11.022
• 发表时间: 2008-12-30
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Carroll MC

Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women.

• DOI: 10.4049/jimmunol.1501684
• 发表时间: 2015-12-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Griesbeck M;Ziegler S;Laffont S;Smith N;Chauveau L;Tomezsko P;Sharei A;Kourjian G;Porichis F;Hart M;Palmer CD;Sirignano M;Beisel C;Hildebrandt H;Cénac C;Villani AC;Diefenbach TJ;Le Gall S;Schwartz O;Herbeuval JP;Autran B;Guéry JC;Chang JJ;Altfeld M
• 通讯作者: Altfeld M

Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation.

• DOI: 10.1038/nature13199
• 发表时间: 2014-06-05
• 期刊: Nature
• 影响因子: 64.8