Unique aspects of respiratory immunity

呼吸道免疫的独特之处

• 批准号: 7807755
• 负责人: Troy D Randall
• 金额: $ 37.38万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7807755
• 关键词: Adult; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Antigens; Architecture; Area; Asthma; Autoimmune Diseases; B-Lymphocytes; Back; Blood; Blood Cells; Breathing; Bronchus-Associated Lymphoid Tissue; Cells; Chronic; Chronic lung disease; Data; Dendritic Cells; Development; Disease; Equilibrium; Exposure to; Failure; Habits; Health; Helper-Inducer T-Lymphocyte; Human; Hyperplasia; Immune response; Immune system; Immunity; Immunology; Inflammation; Inflammatory; Inflammatory Response; Influenza; Kinetics; Lead; Lung; Lung diseases; Lymphocyte; Lymphoid; Lymphoid Tissue; Mediastinal lymph node group; Memory; Morbidity - disease rate; Mus; Neonatal; Organ; Outcome; Pathology; Phenotype; Play; Property; Recruitment Activity; Research; Respiratory System; Respiratory Tract Infections; Respiratory physiology; Respiratory tract structure; Role; Stimulus; Stromal Cells; T memory cell; T-Lymphocyte; Testing; Virus Diseases; base; cell type; chemokine; lymph nodes; migration; mortality; neonate; pathogen; prevent; research study; respiratory; response; scaffold; therapy development; trafficking

The lung is constantly exposed to a variety of inhaled antigens and pathogens to which the immune system must respond. In particular, respiratory immune responses must be robust enough to eliminate respiratory pathogens, but must also be controlled enough so that the resulting inflammation does not interfere with lung function. A failure to achieve balance between immunity and inflammation leads to failed immunity and to a variety of idiopathic, progressive or chronic lung diseases. Understanding the mechanisms that keep pulmonary immunity and the associated inflammatory response in check, and yet prepared to respond quickly to potentially deadly or disease-causing pathogens is important to developing rational approaches to intervening in many pulmonary diseases. However, pulmonary immunology is an understudied area of lung research and little has been done to characterize the pulmonary immune system per se. Local lymphoid tissues, such as inducible Bronchus Associated Lymphoid Tissue (iBALT), are likely to play a central role in respiratory immune responses. However, the role of iBALT in respiratory immunity is poorly understood. Our preliminary data demonstrate that iBALT primes influenza-specific T and B cells in the absence of conventional lymphoid organs. Surprisingly, respiratory immune responses generated exclusively in iBALT lead to less morbidity and mortality, suggesting that iBALT may confer anti-inflammatory properties on local immune responses. In contrast, other studies correlate the presence of iBALT with the pathology associated with autoimmune disease or chronic respiratory infections. Thus, the role of iBALT in respiratory immunity remains enigmatic. Interestingly, respiratory inflammation in neonates appears to more efficiently elicit iBALT than inflammation in adults, suggesting that there is a developmental window for the formation of iBALT. We will test the hypothesis that the formation of iBALT in neonates will permanently change the architecture and function of the lung and that these changes will be manifest as (i) altered sensitivity to respiratory antigens, (ii)changes in the number, phenotype and migratory habits of dendritic cells in the lung, (iii)changes in T cell responses to respiratory antigens and (iv) changes in the outcome of immune responses to respiratory antigens and pathogens. These experiments will lead to a new understanding of how iBALT functions in respiratory immunity. Relevance to human health. The results from these experiments will lead to a new understanding of how iBALT functions in respiratory immunity to innocuous antigens and to pathogens of the respiratory tract. We expect that the results from these experiments will help to develop therapies that take advantage of the beneficial properties of iBALT (by promoting immunie responses to pathogens) and prevent iBALT from exacerbating respiratory pathology (asthma and chronic inflammatory diseases of the lung).

肺部不断地暴露在各种吸入的抗原和病原体中，免疫系统对这些抗原和病原体 必须做出回应。特别是，呼吸道免疫反应必须足够强大，以消除呼吸道 病原体，但也必须得到足够的控制，以使由此产生的炎症不会干扰 肺功能。未能在免疫和炎症之间达到平衡会导致免疫失败和 各种特发性、进行性或慢性肺部疾病。了解保持以下特性的机制 肺免疫和相关炎症反应处于受控状态，但仍做好应对准备 快速找到可能致命或致病的病原体对于开发合理的方法来应对 介入许多肺部疾病。然而，肺部免疫学是一个研究较少的肺部领域。 对肺免疫系统本身的研究和研究很少。局部淋巴组织 组织，如诱导性支气管炎相关淋巴组织(IBALT)，可能在 呼吸道免疫反应。然而，iBALT在呼吸道免疫中的作用还知之甚少。我们的 初步数据显示，iBALT在缺乏流感特异性T和B细胞的情况下启动 常规的淋巴器官。令人惊讶的是，呼吸道免疫反应仅在iBALT中产生 导致较低的发病率和死亡率，这表明iBALT可能赋予局部 免疫反应。相反，其他研究将iBALT的存在与相关的病理联系起来 患有自身免疫性疾病或慢性呼吸道感染。因此，iBALT在呼吸道免疫中的作用 仍然是个谜。有趣的是，新生儿的呼吸道炎症似乎更有效地引发了 IBALT在成人中比炎症更明显，这表明存在发育窗口，以形成 IBALT。我们将检验这一假设，即新生儿iBALT的形成将永久性地改变 肺的结构和功能，这些变化将表现为：(I)改变对 呼吸道抗原，(Ii)树突状细胞的数量、表型和迁移习性的变化 肺，(Iii)T细胞对呼吸道抗原反应的变化和(Iv)免疫结局的变化 对呼吸道抗原和病原体的反应。这些实验将导致对 IBALT如何在呼吸免疫中发挥作用。 与人类健康相关。这些实验的结果将导致对如何 IBALT在呼吸道对无害抗原和病原体的免疫中起作用。我们 期望这些实验的结果将有助于开发利用 IBALT的有益特性(通过促进对病原体的免疫反应)和预防iBALT 加重呼吸道病理(哮喘和慢性肺部炎症性疾病)。