Butler James, Sawtell Amy, Jarrett Simon, Cosgrove Jason, Leigh Roger, Timmis Jon, Coles Mark
Centre for Immunology and Infection, Department of Biology, York, YO10 5DD, UK.
York Computational Immunology Laboratory, York, YO10 5DD, UK.
Adv Exp Med Biol. 2016;915:329-46. doi: 10.1007/978-3-319-32189-9_20.
Immune responses occur as a result of stochastic interactions between a plethora of different cell types and molecules that regulate the migration and function of innate and adaptive immune cells to drive protection from pathogen infection. The trafficking of immune cells into peripheral tissues during inflammation and then subsequent migration to draining lymphoid tissues has been quantitated using radiolabelled immune cells over 40 years ago. However, how these processes lead to efficient immune responses was unclear. Advances in physics (multi-photon), chemistry (probes) and biology (animal models) have provided immunologists with specialized tools to quantify the molecular and cellular mechanisms driving immune function in lymphoid tissues through directly visualising cellular behaviours in 3-dimensions over time. Through the temporal and spatial resolution of multi-photon confocal microscopy immunologists have developed new insights into normal immune homeostasis, host responses to pathogens, anti-tumour immune responses and processes driving development of autoimmune pathologies, by the quantification of the interactions and cellular migration involved in adaptive immune responses. Advances in deep tissue imaging, including new fluorescent proteins, increased resolution, speed of image acquisition, sensitivity, number of signals and improved data analysis techniques have provided unprecedented capacity to quantify immune responses at the single cell level. This quantitative information has facilitated development of high-fidelity mathematical and computational models of immune function. Together this approach is providing new mechanistic understanding of immune responses and new insights into how immune modulators work. Advances in biophysics have therefore revolutionised our understanding of immune function, directly impacting on the development of next generation immunotherapies and vaccines, and is providing the quantitative basis for emerging technology of simulation-guided experimentation and immunotherapeutic design.
免疫反应是由大量不同细胞类型和分子之间的随机相互作用引起的，这些细胞类型和分子调节先天性和适应性免疫细胞的迁移和功能，以驱动对病原体感染的保护。40多年前，人们就已经使用放射性标记的免疫细胞对炎症期间免疫细胞向外周组织的运输以及随后向引流淋巴组织的迁移进行了定量。然而，这些过程如何导致有效的免疫反应尚不清楚。物理学（多光子）、化学（探针）和生物学（动物模型）的进展为免疫学家提供了专门的工具，通过直接在三维空间中随时间可视化细胞行为，来量化驱动淋巴组织中免疫功能的分子和细胞机制。通过多光子共聚焦显微镜的时间和空间分辨率，免疫学家通过量化适应性免疫反应中涉及的相互作用和细胞迁移，对正常免疫稳态、宿主对病原体的反应、抗肿瘤免疫反应以及驱动自身免疫性疾病发展的过程有了新的认识。深度组织成像的进展，包括新的荧光蛋白、更高的分辨率、图像采集速度、灵敏度、信号数量以及改进的数据分析技术，为在单细胞水平上量化免疫反应提供了前所未有的能力。这种定量信息促进了免疫功能的高保真数学和计算模型的发展。这种方法共同为免疫反应提供了新的机制理解，并为免疫调节剂的工作方式提供了新的见解。因此，生物物理学的进展彻底改变了我们对免疫功能的理解，直接影响了下一代免疫疗法和疫苗的开发，并为模拟引导实验和免疫治疗设计的新兴技术提供了定量基础。
