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Cell adhesion is a fundamental feature of multicellular organisms including their defense mechanisms. In the later case in mammals, leukocytes play a central role. They bind bacteria, parasites, viruses, tumor cells, etc. Furthermore, their interactions with the endothelium are of special importance. Generally, lymphocyte adhesion and passage from the bloodstream to the lymphatic system occurs in the high endothelial venules of the lymph nodes. This way the lymphocytes can communicate with each other in the lymphatic system and search for foreign compounds after their recirculation to the bloodstream, thus fulfilling their role in the immune system. The reaction passes through the following steps: 1. Rolling, the flow of cells is slowed down by first making contacts to the endothelium via P-, E-, and L-selectins and their receptors; 2. Adhesion, after activation of leukocyte integrins, firm contacts are established between them and endothelium molecules of the Ig superfamily (e.g., LFA-1, Mac-1, VLA-4); 3. Flattening of the cells and diapedesis, adhering leukocytes crawl to an intercellular junction of the endothelium and then transmigrate to or even through the intercellular matrix. This is mediated by homophilic interactions of PECAM and CD31. (This definition may be outdated - see the DesignNote.)
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