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Fig. 4: Initial generation of an immune response in skin. (1) Langerhans' cells and dermal dendritic cells capture antigen. (2) While antigen is processed and presented on the surface of the APC, maturation occurs with the expression of costimulatory molecules. (3) The APC migrate via the afferent lymphatics to the skin-draining lymph node. (4) In the lymph node, they present the processed antigen to naïve T-cells (CD45RA+) (Fig. 5) causing T-cell maturation, activation and proliferation. (5) Mature activated T-cells (CD45RO+) express CLA antigen. (6) CLA antigen is able to bind to E- and P-selectins expressed by endothelial cells in the dermis. (7) This interaction stimulates T-cells to express LFA-1 and VLA-4 and endothelial cells to produce intercellular and vascular adhesion molecules (ICAM and VCAM). (8) The interaction of these molecules allows the activated T-cells to migrate through the postcapillary venules into the dermis. (9) The activated T-cells can then migrate to areas of antigen expression in the dermis or epidermis. (10) The activated T-cell can secrete cytokines such as IFN-{gamma} or TNF-{alpha} and recruit other immune effector cells, including neutrophils. Photo: Chesley Sheppard