Evening Lecture: Imaging Immunity: Developing a Spatiotemporal Understanding of Host Defense and Disease

Ron Germain, NIAID, Bethesda, United States

Germain, Ronald N.1, Laemmermann, Tim1,2, Uderhardt, Stefan1, , Liu, Zhiduo1, Rudensky, A. Y.3,4, Levine, A. G.3,4, Li, Weizhe1, Radtke, Andrea1, Yu, Weiming1, Pires da silva Baptista, Antonio1, Gerner, Michael Y.1,5

1Laboratory of Systems Biology, NIAID, NIH, Bethesda, MD USA 20892; 2Present address: Max-Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany; 3Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 4Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA;5 Present address: Dept. of Immunology, Univ. of Washington, Seattle, WA.

Ron GermainBackground: Immune responses involve cell-cell interactions within lymphoid tissues, trafficking of activated cells to sites of effector function, and the migration of effector cells within peripheral tissues. To gain insight into the relationships among cell movement, tissue architecture, and immune function, we have used intravital multiphoton microscopy and a novel multiplex immunohistochemical method we have developed called Histo-cytometry.

Observations: Migrating T cells follow stromal pathways in lymph nodes, with chemokine cues facilitating interactions among rare antigen-presenting and antigen-recognizing cells. In tissue sites, effector cells stop when they perceive antigen and undergo transient activation and cytokine release, followed by tuning of their response to existing antigen levels. Innate immune (neutrophil) responses have been dissected at the molecular level. The role of cell localization in both innate and adaptive immunity has also been addressed using Histo-cytometry. With an ability to use as many as 14 different colors and antibodies not only to surface markers but to phospho-proteins and cytokines, and also to conduct imaging in large 3D volumes in a quantitative manner, our multiplex imaging technology facilitates analysis of the phenotype, number, location, signaling state, and function of immune cells and stromal elements in infected, inflamed, or tumor sites. 

Conclusion: This talk will illustrate the power of in situ imaging for the acquisition of a more accurate picture of the molecular, cellular, spatial, and temporal aspects of cell function and signaling events in host immune responses.

This work was supported in part by the Intramural Research Program of the NIH, NIAID.


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