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Imaging Immunity

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Air date: Wednesday, December 9, 2015, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 781, (240 Live, 541 On-demand)
Category: WALS - Wednesday Afternoon Lectures
Runtime: 01:08:04
Description: NIH Director’s Wednesday Afternoon Lecture

G. Burroughs Mider Lecture

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 a more detailed appreciation of the relationships among cell movement, tissue architecture, stromal cell environment, and immune function, we have used intravital multiphoton microscopy and novel multiplex immunohistochemical methods we have developed called Histo-cytometry and Ce3D to analyze immune cell dynamics and tissue micro-anatomy.

The immune system has three major components involving barrier function, innate immunity, and adaptive immunity and the lecture will integrate information on all three levels to develop a comprehensive picture of how the immune system operates to provide host protection against infection. Using dynamic imaging in living animals, we have found that at sites of tissue damage such as the skin, neutrophils that are primary effectors of innate immunity are guided by stimuli from damaged barrier tissue and secondary lipid mediators to develop dense swarms that isolate the damaged area and localize infectious agents. In secondary lymphoid tissues where the adaptive immune response develops, a stromal cell network plays a key role in guiding T lymphocyte trafficking for efficient interaction of rare specific cells with FRC-attached dendritic cells presenting antigens from vaccines or infectious agents. These interactions lead to effector T cell development. After exiting the lymph nodes and then the blood to enter tissue sites, the effector T cells stop on antigen-presenting cells and make mediators that are key to host defense. An important feedback regulatory pathway titrates the effector activity of the T cells so that they do not make more mediators capable of tissue damage than is needed to control the infection.

The role of cell localization in both innate and adaptive immunity has also been addressed using Histo-cytometry that reveals at high resolution the spatial positioning and activation state of cells with complex phenotypes in tissues. 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 an quantitative manner (Ce3D), our multiplex imaging technology is ideally suited to studies of tissue samples from animal models and human patients with respect to the phenotype, number, location, signaling state, and function of immune cells and stromal elements in tissue sites including cancer. Using these static imaging tools, we have discovered the role of dendritic cell positioning in controlling responses to infections and vaccines as well as the localized environment in which regulatory T cells control potential autoimmune responses in normal individuals.

Using these specific examples, this lecture 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 involved in immune responses

About the G. Burroughs Mider Lecture:
Established in 1968 in honor of the first NIH director of laboratories and clinics, the lecture, part of the Wednesday Afternoon Lecture Series and an NIH intramural scientist’s outstanding contributions to biomedical research.

For more information go to https://oir.nih.gov/wals
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NLM Title: Imaging immunity / Ronald N. Germain.
Author: Germain, Ron.
Publisher:
Abstract: (CIT): NIH Director's Wednesday Afternoon Lecture, G. Burroughs Mider Lecture 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 a more detailed appreciation of the relationships among cell movement, tissue architecture, stromal cell environment, and immune function, we have used intravital multiphoton microscopy and novel multiplex immunohistochemical methods we have developed called Histo-cytometry and Ce3D to analyze immune cell dynamics and tissue micro-anatomy. The immune system has three major components involving barrier function, innate immunity, and adaptive immunity and the lecture will integrate information on all three levels to develop a comprehensive picture of how the immune system operates to provide host protection against infection. Using dynamic imaging in living animals, we have found that at sites of tissue damage such as the skin, neutrophils that are primary effectors of innate immunity are guided by stimuli from damaged barrier tissue and secondary lipid mediators to develop dense swarms that isolate the damaged area and localize infectious agents. In secondary lymphoid tissues where the adaptive immune response develops, a stromal cell network plays a key role in guiding T lymphocyte trafficking for efficient interaction of rare specific cells with FRC-attached dendritic cells presenting antigens from vaccines or infectious agents. These interactions lead to effector T cell development. After exiting the lymph nodes and then the blood to enter tissue sites, the effector T cells stop on antigen-presenting cells and make mediators that are key to host defense. An important feedback regulatory pathway titrates the effector activity of the T cells so that they do not make more mediators capable of tissue damage than is needed to control the infection. The role of cell localization in both innate and adaptive immunity has also been addressed using Histo-cytometry that reveals at high resolution the spatial positioning and activation state of cells with complex phenotypes in tissues. 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 an quantitative manner (Ce3D), our multiplex imaging technology is ideally suited to studies of tissue samples from animal models and human patients with respect to the phenotype, number, location, signaling state, and function of immune cells and stromal elements in tissue sites including cancer. Using these static imaging tools, we have discovered the role of dendritic cell positioning in controlling responses to infections and vaccines as well as the localized environment in which regulatory T cells control potential autoimmune responses in normal individuals. Using these specific examples, this lecture 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 involved in immune responses.
Subjects: Image Cytometry
Immunity
Publication Types: Lecture
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Caption Text: Download Caption File
NLM Classification: QW 540
NLM ID: 101674301
CIT Live ID: 17644
Permanent link: https://videocast.nih.gov/launch.asp?19375