Defining the antibody interface between Mycobacterium tuberculosis and host immunity
定义结核分枝杆菌与宿主免疫之间的抗体界面
基本信息
- 批准号:10365049
- 负责人:
- 金额:$ 41.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-23 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAerobicAnaerobic BacteriaAntibodiesAntibody DiversityAntigensBacteriaBacterial InfectionsBindingBiological AssayCD4 Positive T LymphocytesCapillary ElectrophoresisCell physiologyCellsCellular ImmunityCessation of lifeChemicalsChronicCommunicable DiseasesDataDiagnosticDiseaseDisease ProgressionEnvironmentEnzymesExhibitsFab domainFc ReceptorFc domainFlow CytometryGoalsGrowthHumanHumoral ImmunitiesHypoxiaImmuneImmune responseImmunityImmunoglobulin GImmunologyIn VitroIndividualInfectionInflammasomeLinkLysosomesMeasuresMicrobeModelingMolecularMycobacterium tuberculosisMycobacterium tuberculosis antigensOutcomePathway interactionsPatternPhagocytosisPhysiologicalPopulationPropertyPublishingResearchRiskRoleSerodiagnosesSignal PathwaySignal TransductionT-LymphocyteTestingTherapeuticTuberculosisVaccine DesignVaccinesViral AntibodiesVisionWorkadaptive immune responseantibody-dependent cell cytotoxicityantimicrobialbasechronic infectionclinically significantdisease heterogeneityglycosylationin vitro Modelin vivoin vivo Modelinhibitor/antagonistlatent infectionmacrophagemonocytemouse modelpermissivenesspressurepreventreceptorrecruitresponsesmall hairpin RNAtuberculosis immunityvaccine development
项目摘要
Project Summary/Abstract:
Tuberculosis (TB) kills 1.5 million people per year. Efforts to reduce this number have been hindered by the lack
effective diagnostics and a protective vaccine underpinned by gaps in the understanding of the immune response
in TB disease. While cellular immunity is important, the humoral immune response to infection by Mycobacterium
tuberculosis (Mtb) is poorly understood. Antibodies, specifically IgG, are critical components of the adaptive
immune response which have been indispensable in our understanding of infectious diseases and vaccine
development. Antibodies function through the combination of recognizing antigens by the Fab domain and the
recruitment of immune effector responses via the Fc domain. Variability in the Fc domain by isotype, subclass,
and post translational glycosylation impact engagement with Fc receptors on immune cells that alter function in
clinically significant manners. We have published that the antibody Fc domain diverges between individuals with
latent infection who appear healthy and able to restrict bacteria compared to active TB disease which is
permissive to Mtb replication. These distinctions are linked to differential Mtb burden in an in vitro primary human
monocyte derived macrophage model of infection. How exactly antibodies might function in this context and its
physiological relevance are questions that this proposal begins to address. The specific aims are 1: Determine
how the Mtb antigenic repertoire impacts polyclonal IgG functions, 2: Identify the macrophage pathways by which
the IgG Fc modulates Mtb survival, 3: Examine the in vivo effect of polyclonal IgG on chronic Mtb infection. The
scientific objective of this proposal is to determine how polyclonal IgG contributes to restrictive and permissive
host states for Mtb. The central hypothesis is that polyclonal IgG from individuals with active TB disease induces
a host state permissive to bacterial growth. The overall goal is to understand fundamental mechanisms of
humoral immunity in TB through antibodies to inform diagnostic, therapeutic and vaccine design.
项目概要/摘要:
结核病每年造成150万人死亡。减少这一数字的努力因缺乏
有效的诊断和保护性疫苗,以免疫反应的理解为基础
在结核病中。虽然细胞免疫是重要的,但对分枝杆菌感染的体液免疫应答是重要的。
结核病(Mtb)是知之甚少。抗体,特别是IgG,是适应性免疫系统的关键组成部分。
免疫反应是我们理解传染病和疫苗所不可缺少
发展抗体通过由Fab结构域识别抗原和由Fab结构域识别抗原的组合来发挥功能。
通过Fc结构域募集免疫效应子应答。Fc结构域的同种型、亚类、
和翻译后糖基化影响与免疫细胞上Fc受体的接合,
有临床意义的举止我们已经发表了抗体Fc结构域在个体之间存在差异,
与活动性结核病相比,
允许Mtb复制。这些差异与体外原代人结核分枝杆菌负荷差异有关。
单核细胞衍生的巨噬细胞感染模型。抗体在这种情况下是如何发挥作用的,
生理相关性是这个建议开始解决的问题。具体目标是:1.确定
Mtb抗原库如何影响多克隆IgG功能,2:确定巨噬细胞途径,
IgGFc调节Mtb存活。3:检查多克隆IgG对慢性Mtb感染的体内作用。的
该提案的科学目的是确定多克隆IgG如何有助于限制性和允许性
Mtb的东道国。中心假设是来自活动性结核病个体的多克隆IgG诱导了
允许细菌生长的宿主状态。总的目标是了解的基本机制,
结核病的体液免疫通过抗体来告知诊断、治疗和疫苗设计。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Lenette Lu其他文献
Lenette Lu的其他文献
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{{ truncateString('Lenette Lu', 18)}}的其他基金
Defining the antibody interface between Mycobacterium tuberculosis and host immunity
定义结核分枝杆菌与宿主免疫之间的抗体界面
- 批准号:
10493365 - 财政年份:2021
- 资助金额:
$ 41.68万 - 项目类别:
Defining the antibody interface between Mycobacterium tuberculosis and host immunity
定义结核分枝杆菌与宿主免疫之间的抗体界面
- 批准号:
10672290 - 财政年份:2021
- 资助金额:
$ 41.68万 - 项目类别:
Antibody Mediated Mechanisms of Immune Modulation in Tuberculosis
结核病免疫调节的抗体介导机制
- 批准号:
9294245 - 财政年份:2017
- 资助金额:
$ 41.68万 - 项目类别:
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