Understanding how the immune system mounts an effective but highly regulated response to foreign pathogens is essentially a problem in systems cell biology. Individual cells, such as T lymphocytes, dendritic cells, and B lymphocytes, must carry out a series of complex tasks individually.
At the same time, they must coordinate their efforts to generate antibodies and cytotoxic responses to pathogens while avoiding damage to the organism itself. Various of our lab groups are at the forefront of this emerging interface, revealing not only critical insights into the underlying mechanisms of the immune response, but also unexpected and fundamental new pieces of cell biology. For example, Cell Biology labs have been among the first to demonstrate how peptide antigens are generated in the cytosol then translocated post-translationally across the ER membrane for loading onto MHC class I molecules. They have also elucidated how dendritic cells respond to inflammatory stimuli enabling their converstion from cells adapted for antigen uptake to cells specialized for antigen degradation and peptide-MHC formation. Other topics include the mechanism of granule secretion in T cells, immunological synapse function, and anti-viral mechanisms. In conjunction with the Section of Immunobiology, the Department has established Yale Medical School as a hotbed of activity in these and related areas. The work is exciting not only for its fundamental aspects, but also because it is directly relevant to the understanding and treatment of a variety of human disorders.
