The dynamics of granuloma formation in tuberculosis

描述（由申请人提供） 这个建议的目的是解释肉芽肿的形成， 结核分枝杆菌感染。 了解肉芽肿形成 和功能将阐明主要的免疫机制， 肺结核感染。 我们的目标是模拟肉芽肿的过程 在时空尺度上形成，并以时间推移的方式呈现结果 电影格式。 这将产生一个交互式工具，以研究 肉芽肿形成和功能中的特异性免疫元素。 发展 人类感染的虚拟模型将允许整合过多的 趋化因子、细胞因子、细胞内流信息和其他相关信息 免疫因子，如实验系统产生的。 为此， 强大的技术（例如，微阵列）可用于获得 全面的基因表达数据 用这些方法来测量表达 在非人类灵长类动物和小鼠的肉芽肿中， 确定哪些免疫介质参与肉芽肿形成， 它们在地层中表达的时间，以及它们的位置 在肉芽肿中。 进一步的研究将表明哪些细胞类型是 表示哪些中介。 我们的具体目标是：（1）确定 参与免疫调节的宿主免疫元件的时空表达 使用基因表达工具在小鼠模型中的肉芽肿形成 （2）确定宿主免疫的时空表达 使用基因表达工具参与肉芽肿形成的元件 小鼠结核模型（3）测定肉芽肿的动态变化 使用肉芽肿的数学模型在人类中的形成和功能 结核病的反应。 通过这种独特的方法， 将确定控制肉芽肿形成的多种因素。 将确定支配这些相互作用的关键参数。 的能力 综合模型中实验产生的数据， 对肉芽肿形成动力学的理解， 它的部分。

DESCRIPTION (provided by applicant) The goal of this proposal is to explain the formation of granuloma in infection with Mycobacterium tuberculosis. Understanding granuloma formation and function will elucidate the primary immune mechanism for controlling tuberculosis infection. Our goal is to simulate the process of granuloma formation on a spatio-temporal scale and present the results in a time-lapse movie format. This will yield an interactive tool to study the role of specific immune elements in granuloma formation and function. Development of a virtual model of human infection will allow for integration of the plethora of chemokine, cytokine, cellular influx information and other relevant immunological factors, as generated by experimental systems. To this end, powerful techniques (e.g., microarrays) are available for obtaining comprehensive gene expression data. Using these methods to survey expression within the granulomas of non-human primates and mice will enable us to determine which immunological mediators are involved in granuloma formation, what the timing of their expression is in the formation, and their location within the granuloma. Further studies will indicate which cell-types are expressing which mediators. Our specific aims are to: (1) Identify the temporal and spatial expression of host immune elements participating in granuloma formation using gene expression tools in murine models of tuberculosis (2) Identify the temporal and spatial expression of host immune elements participating in granuloma formation using gene expression tools in murine models of tuberculosis (3) Determine the dynamics of granuloma formation and function in humans using mathematical models of the granuloma response in tuberculosis. Through this unique approach, the interaction of multiple factors that control the formation of the granuloma will be defined. Key parameters governing these interactions will be identified. The ability to synthesize the data generated by the experiments in the models allows for an understanding of the dynamics of granuloma formation as more than the sum of its parts.