Interleukins tell lymphocytes what to do by eliciting a transcriptional program that allows lymphocytes to acquire specialized effector functions. Chemokines, on the other hand, tell leukocytes where to go. Many cells emit chemotactic cues in the form of chemokines. When tissue damage occurs, resident fibroblasts produce a chemokine, IL-8, that attracts neutrophils to the site of damage. The regulation of lymphocyte traffic within lymph nodes is essential for dendritic cells to attract T cells, and for T cells and B cells to meet. These trafficking steps are all controlled by chemokines.

There are approximately 40 distinct chemokines and more than a dozen chemokine receptors. One chemokine may bind to more than one receptor, and a single receptor can bind several different chemokines. This flexibility creates the possibility of generating a combinatorial code of chemotactic cues of great complexity. This code is used to guide the navigation of leukocytes from where they are generated, in the bone marrow, into the bloodstream for transport to their target destination.

Some chemokines direct lymphocytes to leave the circulation and take up residence in lymphoid organs. These migrations contribute to the population of lymphoid organs with the required sets of lymphocytes. Because these movements occur as part of normal lymphoid development, such chemokines are referred to as homeostatic chemokines. Those chemokines that serve the purpose of recruiting leukocytes to sites of inflammation and tissue damage are referred to as inflammatory chemokines.

Chemokine receptors are G protein–coupled receptors that function as an essential component of the regulation of cell adhesion and cell migration. Leukocytes that travel through blood vessels do so at high speed and are exposed to high hydrodynamic shear forces. For a leukocyte to traverse the endothelium and take up residence in a lymph node or seek out a site of infection in tissue, it must first slow down, a process that requires interactions of glycoprotein surface receptors called selectins with their ligands on the surfaces of leukocytes, which are mostly carbohydrate in nature. If chemokines are adsorbed to the extracellular matrix, and if the leukocyte possesses a receptor for those chemokines, activation of its chemokine receptor elicits a signal that allows integrins carried by the leukocyte to undergo a conformational change. This change results in an increase in the affinity of the integrin for its ligand and causes firm arrest of the leukocyte. The leukocyte may now exit the blood vessel by a process known as extravasation (see Figure 20-40).