2 part I Immune Effector mechanisms TABLE 15-1 Some interactions between cell-adhesion molecules implicated in leukocyte extravasation" Step involving Receptor on cells Expressio endothelium iteraction Main function CLA or ESL-1 Effector t cells E-selectin Tethering/rolling Homing to skin and migration into inflamed tissue All leukocytes GlyCAM-1 Tethering/rolling ymphocyte recirculation CD34 via HEVs to peripheral lymph MAdCAM-1 nodes and migration into inflamed tertiary sites LFA-1(aLB2) Leukocyte CAM1,2,3 Adhesion/arrest General role in lymphocyte extravasation via HEVs and leukocyte migration into LPAM-1(a4B7) Effector t cells MAdCAM-1 Rolling/adhesion Homing of T cells to gut via VCAM-1 mucosal HEV; migration into inflamed tissue Mac-1 (aMB2) Monocytes VCAM-1 Monocyte migration into inflamed tissue PSGL-1 Neutrophils E and Tethering/rolling Neutrophil migration into P-selectin VLA-4(a4B1) Neutrophils VCAM-1 Rolling/adhesion General role in leukocyte T cells MAdCAM-1 migration into inflamed tissue VLA-6(a6B1) T cells Homing of progenitor T cells to thymus: possible role in T-cell homing to nonmucosal sit and leukocyte CAMs belong to four groups of proteins as shown in Figure 15-2. In general, molecules in the integrin family bind to lg- superfamily CAMs, and molecules in the selectin family bind to mucin-like CAMs. Members of the selectin and mucin-like families can be expressed on both leukocytes and ndothelial cells, whereas integrins are expressed only on leukocytes, and Ig.super CAMs are expressed only on endothelium See Figures 15-3a and 15-7for an illustration of steps in the extravasation process bound cells are found adhering to HEVs, even though HEVs like family(GlyCAM-1 and CD34), and the immunoglobulin account for only 1%-2% of the total area of the frozen sec- superfamily (ICAM-1, ICAM-2, ICAM-3, VCAM-1, and tion(Figure 15-4c) MAdCAM-1). Some of these adhesion molecules are distrib It has been estimated that as many as 1.4 X 10" lympho- uted in a tissue-specific manner. These tissue-specific adhe every second through HEVs into a single sion molecules have been called vascular addressins(VAs) cytes extravasate development and maintenance of HEVs in because they serve to direct the extravasation of different lymphoid organs is influenced by cytokines produced in re- populations of recirculating lymphocytes to particular lym- sponse to antigen capture. For example, HEVs fail to develop phoid organs in animals raised in a germ-free environment. The role of ntigenic activation of lymphocytes in the maintenance of Lymphocyte Homing Is Directed HEVs has been demonstrated by surgically blocking the af ferent lymphatic vasculature to a node, so that antigen entry al- by Receptor Profiles and Signals to the node is blocked. Within a short period of time, the The general process of lymphocyte extravasation is similar to HEVs show impaired function and eventually revert to a neutrophil extravasation. An important feature distinguish more flattened morphology ing the two processes is that different subsets of lymphocytes High-endothelial venules express a variety of cell-adhesion migrate differentially into different tissues. This process is molecules. Like other vascular endothelial cells, HEVs express called trafficking, or homing. The different trafficking pat CAMs of the selectin family (E-and P-selectin), the mucin- terns of lymphocyte subsets are mediated by unique combibound cells are found adhering to HEVs, even though HEVs account for only 1%–2% of the total area of the frozen sec￾tion (Figure 15-4c). It has been estimated that as many as 1.4  104 lympho￾cytes extravasate every second through HEVs into a single lymph node. The development and maintenance of HEVs in lymphoid organs is influenced by cytokines produced in re￾sponse to antigen capture. For example, HEVs fail to develop in animals raised in a germ-free environment. The role of antigenic activation of lymphocytes in the maintenance of HEVs has been demonstrated by surgically blocking the af￾ferent lymphatic vasculature to a node, so that antigen entry to the node is blocked. Within a short period of time, the HEVs show impaired function and eventually revert to a more flattened morphology. High-endothelial venules express a variety of cell-adhesion molecules. Like other vascular endothelial cells, HEVs express CAMs of the selectin family (E- and P-selectin), the mucin￾like family (GlyCAM-1 and CD34), and the immunoglobulin superfamily (ICAM-1, ICAM-2, ICAM-3, VCAM-1, and MAdCAM-1). Some of these adhesion molecules are distrib￾uted in a tissue-specific manner. These tissue-specific adhe￾sion molecules have been called vascular addressins (VAs) because they serve to direct the extravasation of different populations of recirculating lymphocytes to particular lym￾phoid organs. Lymphocyte Homing Is Directed by Receptor Profiles and Signals The general process of lymphocyte extravasation is similar to neutrophil extravasation. An important feature distinguish￾ing the two processes is that different subsets of lymphocytes migrate differentially into different tissues. This process is called trafficking, or homing. The different trafficking pat￾terns of lymphocyte subsets are mediated by unique combi- 342 PART III Immune Effector Mechanisms TABLE 15-1 Some interactions between cell-adhesion molecules implicated in leukocyte extravasation* Ligands on Step involving Receptor on cells Expression endothelium interaction† Main function CLA or ESL-1 Effector T cells E-selectin Tethering/rolling Homing to skin and migration into inflamed tissue L-selectin All leukocytes GlyCAM-1, Tethering/rolling Lymphocyte recirculation CD34, via HEVs to peripheral lymph MAdCAM-1 nodes and migration into inflamed tertiary sites LFA-1 (L2) Leukocyte ICAM-1, 2, 3 Adhesion/arrest General role in lymphocyte subsets extravasation via HEVs and leukocyte migration into inflamed tissue LPAM-1 (47) Effector T cells, MAdCAM-1, Rolling/adhesion Homing of T cells to gut via monocytes VCAM-1 mucosal HEV; migration into inflamed tissue Mac-1 (M2) Monocytes VCAM-1 — Monocyte migration into inflamed tissue PSGL-1 Neutrophils E- and Tethering/rolling Neutrophil migration into P-selectin inflamed tissue VLA-4 (41) Neutrophils, VCAM-1 Rolling/adhesion General role in leukocyte T cells, MAdCAM-1, migration into inflamed tissue monocytes fibronectin VLA-6 (61) T cells Laminin — Homing of progenitor T cells to thymus; possible role in T-cell homing to nonmucosal sites *Most endothelial and leukocyte CAMs belong to four groups of proteins as shown in Figure 15-2. In general, molecules in the integrin family bind to Ig-superfamily CAMs, and molecules in the selectin family bind to mucin-like CAMs. Members of the selectin and mucin-like families can be expressed on both leukocytes and endothelial cells, whereas integrins are expressed only on leukocytes, and Ig-superfamily CAMs are expressed only on endothelium. † See Figures 15-3a and 15-7 for an illustration of steps in the extravasation process.