Summary

* Leukocyte migration from blood into tissues occurs through postcapillary venules and depends on adhesion molecules expressed on the leukocytes and vascular endothelial cells as well as chemokines.

* Selectins are carbohydrate-binding adhesion molecules that mediate low-affinity interactions of leukocytes with endothelial cells, as the first step in leukocyte migration from blood into tissues. E-selectin and P-selectin are expressed on activated endothelial cells and bind to selectin ligands on leukocytes, and L-selectin is expressed on leukocytes and binds ligands on endothelial cells.

* Integrins are a large family of adhesion molecules, some of which mediate tight adhesion of leukocytes with activated endothelium, as a critical step in leukocyte migration from blood into tissues. The important leukocyte integrins include LFA-1 and VLA-4, which bind to ICAM-1 and VCAM-1, respectively, on endothelial cells.

* Leukocyte migration from blood into tissues involves a series of sequential steps of interactions with endothelial cells, starting with low-affinity leukocyte binding to and rolling along the endo-thelial surface (mediated by selectins and selectin ligands). Next, the leukocytes become firmly bound to the endothelium, through interactions of leukocyte integrins binding to Ig superfamily ligands on the endothelium. Integrin binding is enhanced by chemokines, produced at the site of infection, that bind to receptors on the leukocytes.

* Lymphocyte recirculation is the process by which naive lymphocytes continuously migrate from blood into secondary lymphoid organs through HEVs, back into the blood through lymphatics, and into other secondary lymphoid organs. This process maximizes the chance of naive T cell encounter with the antigen it recognizes and is critical for the initiation of immune responses.

* Naive B and T cells migrate preferentially to lymph nodes; this process is mediated by binding of L-selectin on lymphocytes to peripheral lymph node addressin on HEVs in lymph nodes and by the CCR7 receptor on the lymphocytes that binds to the chemokines CCL19 and CCL21, which are produced in lymph nodes.

* The effector and memory lymphocytes that are generated by antigen stimulation of naive cells exit the lymph node by a process dependent on the summary 53

sphingosine-1 phosphate receptor on the lymphocytes and a gradient of sphingosine 1 phosphate. Effector T cells have decreased L-selectin and CCR7 expression but increased expression of inte-grins and E-selectin and P-selectin ligands, and these molecules mediate binding to endothelium at peripheral inflammatory sites. Effector and memory lymphocytes also express receptors for chemokines that are produced in infected peripheral tissues.

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