Defined Native Antigens and Immunity to tuberculosis

确定的天然抗原和结核病免疫

• 批准号: 6746858
• 负责人: IAN M ORME
• 金额: $ 28.87万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6746858
• 关键词: Mycobacterium tuberculosis; T lymphocyte; aerosols; bacteria infection mechanism; bacterial antigens; bactericidal immunity; cytotoxic T lymphocyte; delayed hypersensitivity; flow cytometry; gene targeting; helper T lymphocyte; immunocytochemistry; immunologic memory; interferon gamma; laboratory mouse; passive immunization; tuberculosis

DESCRIPTION (provided by applicant): The purpose of this request for competing continuation funding is to continue our work on dissecting and defining the fundamental nature of the host immune response in the lung after exposure of mice to a realistic low dose aerosol infection with Mycobacterium tuberculosis. While our past work has contributed significantly to the definition of the acquired response, it is now clear that early resistance in the lung to infection is regulated by potentially redundant layers of very poorly understood innate immune mechanisms in addition to the better-characterized TH1 protective response. In the next funding period we propose a series of experiments to define these early mechanisms more clearly using a variety of approaches including flow cytometry, high speed fluorescence-activated cell sorting, histology, and immunohistochemistry. In our first Aim we will continue to try to identify sources of IFN-gamma that appear very early during the course of the infection, concentrating on the role of NK/NKT cell subsets and their potential restriction by Class-Ib MHC encoded molecules. In a second Aim, we propose to continue studies that are constructed to define the basic requirements needed to adequately and efficiently focus lymphocytes into the infected lungs, using a combination of flow cytometric analysis and sorting followed by adoptive transfer of tagged specific T cell subsets and subsequent tracking. Finally, we propose a fresh look at the memory T cell response in tuberculosis, specifically concentrating on parameters such as longevity, turnover, and potential cell surface marker reversion, primarily defined by flow cytometry. The proposed work will draw upon the broad expertise of various members of the Mycobacteria Research Laboratories at Colorado State University, as well as several eminent consultants and advisers.

描述（由申请人提供）：本次竞争性持续资助请求的目的是继续我们的工作，剖析和定义小鼠暴露于结核分枝杆菌的真实低剂量气溶胶感染后肺部宿主免疫反应的基本性质。虽然我们过去的工作对获得性反应的定义做出了重大贡献，但现在很明显，除了更好表征的 TH1 保护反应之外，肺部对感染的早期抵抗力还受到我们知之甚少的先天免疫机制的潜在冗余层的调节。 。在下一个资助期内，我们提出了一系列实验，使用流式细胞术、高速荧光激活细胞分选、组织学和免疫组织化学等多种方法更清楚地定义这些早期机制。在我们的第一个目标中，我们将继续尝试识别感染过程中早期出现的 IFN-γ 来源，重点关注 NK/NKT 细胞亚群的作用及其受到 Ib 类 MHC 编码分子的潜在限制。在第二个目标中，我们建议继续进行研究，以确定充分有效地将淋巴细胞集中到受感染肺部所需的基本要求，使用流式细胞分析和分选相结合，然后过继转移标记的特定 T 细胞亚群和后续跟踪。最后，我们建议重新审视结核病中的记忆 T 细胞反应，特别关注寿命、周转率和潜在细胞表面标志物逆转等参数，这些参数主要由流式细胞术定义。拟议的工作将利用科罗拉多州立大学分枝杆菌研究实验室各成员以及几位著名顾问和顾问的广泛专业知识。