Sustained adaptive immunity in the mucosa

粘膜的持续适应性免疫

• 批准号: 9055619
• 负责人: Linda S Cauley
• 金额: $ 47.55万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9055619
• 关键词: Adjuvant; Adsorption; Alveolus; Antibodies; Antibody Formation; Antibody Response; Antigen Presentation; Antigen-Antibody Complex; Antigens; Apoptosis; Area; B-Lymphocytes; Blood Circulation; CD8B1 gene; Cellular Immunity; Cessation of life; Characteristics; Chronic; Complex; Cytotoxic T-Lymphocytes; Data; Environment; Epithelium; Gene Expression; Goals; Government; Health; Human; Immigration; Immune; Immune response; Immunity; Immunoglobulin A; Immunoglobulin Class Switching; Infection; Infectious Agent; Inflammation; Inflammatory Response; Influenza; Instruction; Kinetics; Life; Longevity; Lung; Lymphocyte; Mass Vaccinations; Mediating; Membrane; Methods; Modeling; Mucous Membrane; Nutrient; Pattern; Peptides; Peripheral; Play; Population; Predisposition; Principal Investigator; Process; Production; RNA; Reaction; Reagent; Recovery; Regulation; Residual state; Respiratory System; Respiratory tract structure; Role; Signal Transduction; Source; Staining method; Stains; Structure of germinal center of lymph node; Surface; T-Lymphocyte; T-Lymphocyte Epitopes; T-Lymphocyte Subsets; Testing; Time; Tissues; Transforming Growth Factor beta; Vaccination; Vaccines; Variant; Viral; Virus; Virus Diseases; adaptive immunity; biodefense; chemokine; cytokine; immune activation; influenza virus strain; influenzavirus; innovation; lymph nodes; microbial; migration; pathogen; prevent; programs; respiratory infection virus; respiratory virus; response

The mucosal surfaces are covered by a thin epithelium which is adapted for selective adsorption of essential nutrients, but is a weak physical barrier against the outside environment. Because this epithelium can be easily breached many infectious agents use the mucosal tissues as gateways into the body. These pathogens include several highly pathogenic respiratory viruses which pose a constant threat to human health. The fragile membranes ofthe alveoli make the lungs particulariy vulnerable to immune damage. We will use a heterosubtypic reinfection model to examine the mechanisms that help protect the lungs from these infections. Previous studies have shown that local populations of cytotoxic T lymphocytes (CTL) and IgA antibodies in the respiratory tract can provide immunity between different stains of influenza virus. Our data indicate that these mechanisms are facilitated by mild antigen-driven inflammation, which helps pathogen-specific CTL stay near the mucosal surface between repeated viral infections and augments local antibody production. The goals ofthe current study are to investigate how a tightly regulated cytokine response promotes enduring T and B cell mediated heterosubtypic immunity. We will focus on the cytokines that trigger innate immune activation, as well as long-term TGF-beta production which plays a pivotal role in immune regulation in the lungs. RELEVANCE (See instructions): Influenza viruses are highly contagious pathogens that are in constant circulation in human populations. High death tolls make these infections a top priority for mass vaccination programs but accumulating data indicate that the current vaccination approaches are not optimized to generate enduring immunity. Our data indicate that T cell mediated immunity in the lungs can be prolonged by a mild inflammatory response.

粘膜表面被薄薄的上皮覆盖，该上皮适合选择性吸附必不可少的 营养素，但是针对外部环境的弱物理障碍。因为这个上皮可以是 很容易违反许多传染性剂，将粘膜组织用作进入人体的门户。这些 病原体包括几种高度致病的呼吸道病毒，对人构成持续威胁 健康。肺泡的脆弱膜使肺部尤其容易受到免疫损伤。我们 将使用异源性再感染模型来检查有助于保护肺部免受的机制 这些感染。先前的研究表明，细胞毒性T淋巴细胞（CTL）和 呼吸道中的IgA抗体可以在流感病毒的不同污渍之间提供免疫力。我们的 数据表明这些机制是通过轻度抗原驱动的炎症促进的，这有助于 病原体特异性的CTL保持在反复的病毒感染之间的粘膜表面附近 抗体产生。当前研究的目标是研究如何严格调节的细胞因子 反应促进了持续的T和B细胞介导的异源性免疫。我们将专注于细胞因子 这引发了先天免疫激活以及长期的TGF-β产生，在 肺部的免疫调节。 相关性（请参阅说明）： 流感病毒是人群中持续循环的高度传染性病原体。 高死亡人数使这些感染成为大规模疫苗接种计划的重中之重，但积累了数据 表明当前的疫苗接种方法未被优化以产生持久的免疫力。我们的数据 表明T细胞介导的肺部免疫力可以通过轻度炎症反应延长。