Cell Biology of the Immune System
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 conversation 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.
Cell Biology of Host Pathogen Interactions
Microbial pathogens, particularly those that have sustained a long-standing association with their hosts, have evolved extremely complex adaptations to secure their own replication and survival. The study of the cell biology and immunobiology of host/pathogen interactions is emerging as a key area of infectious disease research in the post-genomic era.
Recent advances are allowing the understanding of the intimate details of the functional, molecular, or in some cases even the atomic interface, between microbial pathogens and their hosts. A surprising finding from this level of understanding is that host/pathogen interactions are most often best characterized by their refinement and complexity than for their potential to cause harm. Many microbial products, often evolved to precisely mimic host cell determinants, have the capacity to modulate cellular functions. The study of these products most often illuminates not only the mechanisms by which pathogens subvert host cellular process but also bring in unique insight into the cell processes themselves.
In conjunction with the Sections of Microbial Pathogenesis and Immunobiology, many laboratories in our program are conducting research at the fore front of this exciting area of investigation. These studies range from the mechanisms by which pathogens harness the actin cytoskeleton or the membrane repair machinery to mediate their own uptake into host cells, to the different ways by which microbial pathogen subvert vesicular trafficking pathways to avoid antigen presentation or their delivery into harmful intracellular compartments.