In order to be able to mount an effective response against a foreign challenge, the immune system orchestrates precise and regulated interactions between different cell types. Physical interactions must therefore occur between cells, such as between T and B lymphocytes or between T lymphocytes and monocytes. These interactions are mediated by a multitude of adhesion molecules. These cell-cell interactions also provide important intracellular signals to both interacting cells via the engagement of multiple receptors and ligands (or counter-receptors). Furthermore, the directed migration or homing of lymphocytes to specific anatomic sites is also mediated by multiple adhesion receptors interacting with ligands on endothelial cells and in the extracellular matrix (ECM). Consequently, adhesion molecules play a vital role in all aspects of lymphocyte function, from the local cell-to-cell contacts that result in the response of a specific T cell to foreign antigen to the more regional interactions that result in specific patterns of migration in vivo.