PART Immune Effector mechanisms Naive t cell Mucosal-homing Skin- homing effector t cell effector t cel CLA L-selectin L-selectin ICAM-1( CD34 GlyCAM-1 d LPAM-1 E-selectin ICAM-1 MAdCAM-1 Intestinal lamina propria Skin dermal venule endothelium Teri FIGURE Examples of homing receptors and vascular addres- pressed on HEV cells. (b, c)Various subsets of effector T cells express sins involved in selective trafficking of naive and effector T cells.(a)Naive high levels of particular homing receptors that allow them to home T cells tend to home to secondary lymphoid tissues through their HEv to endothelium in particular tertiary extralymphoid tissues. The initial regions. The initial interaction involves the homing receptor L-selectin interactions in homing of effector T cells to mucosal and skin sites are and mucin -like cell-adhesion molecules such as CD34 or GlyCAM-1 ex- illustrated. region of the secondary lymphoid tissue. During this phase, home to these sites. Inflamed endothelium expresses a num- called the shut-down phase, the antigen-specific lympho- ber of adhesion molecules, including E-and P-selectin and cytes cannot be detected in the circulation(Figure 15-6). the Ig-superfamily molecules VCAM-1 and ICAM-1, that Rapid proliferation and differentiation of naive cells occurs bind to the receptors expressed at high levels on memory and during the shut-down phase. The effector and memory cells effector cells that are generated by this process then leave the lymphoid tis- sue and begin to recirculate Effector and Memory Lymphocytes Adopt Different Trafficking Patterns hut-down phase The trafficking patterns of effector and memory lympho- 2 cytes differ from those of naive lymphocytes Effector cells g tend to home to regions of infection by recognizing inflamed fg vascular endothelium and chemoattractant molecules that o e are generated during the inflammatory response. Memory lymphocytes, on the other hand, home selectively to the type e of tissue in which they first encountered antigen. Presumably this ensures that a particular memory cell will return to the issue where it is most likely to reencounter a subsequent threat by the antigen it recognizes Effector and memory cells express increased levels of cer- Days following antigen exposure tain cell-adhesion molecules. such as lfa-1 that interact with ligands present on tertiary extralymphoid tissue(such FIGURE 15-6 T-cell activation in the paracortical region of a lymph as skin and mucosal epithelia)and at sites of inflammation, node results in the brief loss of lymphocyte recirculation. During this allowing effector and memory cells to enter these sites. Naive shut-down phase, antigen-specific T cells cannot be detected leaving cells lack corresponding cell-adhesion molecules and do not the node in the efferent lymphregion of the secondary lymphoid tissue. During this phase, called the shut-down phase, the antigen-specific lympho￾cytes cannot be detected in the circulation (Figure 15-6). Rapid proliferation and differentiation of naive cells occurs during the shut-down phase. The effector and memory cells that are generated by this process then leave the lymphoid tis￾sue and begin to recirculate. Effector and Memory Lymphocytes Adopt Different Trafficking Patterns The trafficking patterns of effector and memory lympho￾cytes differ from those of naive lymphocytes. Effector cells tend to home to regions of infection by recognizing inflamed vascular endothelium and chemoattractant molecules that are generated during the inflammatory response. Memory lymphocytes, on the other hand, home selectively to the type of tissue in which they first encountered antigen. Presumably this ensures that a particular memory cell will return to the tissue where it is most likely to reencounter a subsequent threat by the antigen it recognizes. Effector and memory cells express increased levels of cer￾tain cell-adhesion molecules, such as LFA-1, that interact with ligands present on tertiary extralymphoid tissue (such as skin and mucosal epithelia) and at sites of inflammation, allowing effector and memory cells to enter these sites. Naive cells lack corresponding cell-adhesion molecules and do not home to these sites. Inflamed endothelium expresses a num￾ber of adhesion molecules, including E- and P-selectin and the Ig-superfamily molecules VCAM-1 and ICAM-1, that bind to the receptors expressed at high levels on memory and effector cells. 344 PART III Immune Effector Mechanisms (a) Naive T cell L-selectin L-selectin CD34 GlyCAM-1 HEV Tertiary extralymphoid tissue LFA-1 LPAM-1 ICAM-1 E-selectin CLA (b) L-selectin LFA-1 ICAM-1 (c) Mucosal-homing effector T cell Skin-homing effector T cell Intestinal lamina propria endothelium Skin dermal venule endothelium MAdCAM-1 SS SS SS SS SS SS SS SS SS SS SS SS SS FIGURE 15-5 Examples of homing receptors and vascular addres￾sins involved in selective trafficking of naive and effector T cells. (a) Naive T cells tend to home to secondary lymphoid tissues through their HEV regions. The initial interaction involves the homing receptor L-selectin and mucin-like cell-adhesion molecules such as CD34 or GlyCAM-1 ex￾pressed on HEV cells. (b, c) Various subsets of effector T cells express high levels of particular homing receptors that allow them to home to endothelium in particular tertiary extralymphoid tissues. The initial interactions in homing of effector T cells to mucosal and skin sites are illustrated. 2468 Days following antigen exposure Shut-down phase Antigen-specific T cells in efferent lymph FIGURE 15- 6 T-cell activation in the paracortical region of a lymph node results in the brief loss of lymphocyte recirculation. During this shut-down phase, antigen-specific T cells cannot be detected leaving the node in the efferent lymph