Imaging-based analysis of adaptive immune responses
The adaptive immune system protects us from harmful microbial infections and cancer, while providing life-long immunity after vaccination. To accomplish this extraordinary feat, cellular components of the immune system, T and B cells, continuously interact with antigen-presenting cells (APCs) in lymphoid organs. A well-studied example are naïve T cells interactions with dendritic cells (DCs), the most powerful APCs for this subset. This leads to T cell activation, division and invasion of infected organs and contributes decisively to pathogen or tumor elimination. While the general principle of such adaptive immune responses is well established, little is known on how this remarkable process unfolds in the context of tissue architecture and cellular dynamics.
Our laboratory is using imaging-based methods, in combination with more conventional methods such as multicolor flow cytometry and functional in vitro assays, to “shed light” on the molecular and cellular processes that govern adaptive immune responses. We follow three lines of investigation:
- We are examining T cell-DC interactions using transgenic lymphocytes lacking of one or more signaling or adhesion molecules, using mainly twophoton microscopy (2PM) of lymphoid tissue. Using software-based analysis of key parameters, we determine the critical decision-making steps at the onset of immune responses.
- We follow T cells at their effector sites, for example in exocrine glands, skin and tumors of mammary gland and observe how these cells contribute to host protection. A special focus is on tissue-resident memory T cells that provide a first line of defense against reinfection.
- We are applying large-scale imaging techniques, Optical Projection Tomography (OPT) and Selective Plane Illumination Microscopy (SPIM) for a quantitative analysis of adaptive immune responses by visualizing the entire 3D structure of lymph nodes and other organs during inflammation.
The combination of these approaches permits to obtain unprecedented insight into the dynamic nature of the adaptive immune system.