Inflammation at several degrees can be triggered by infectious agents but also by endogenous molecules
upon tissue damage. Most of the time, innate immune mechanisms control harmful agents; however, if these strategies succumb, the mounting of immune responses must take place to maintain homeostasis. First, an infected or damaged tissue recruits different leukocytes by producing pro-inflammatory mediators and chemokines. The first cells to be recruited to an injured tissue are the neutrophils which in humans represent the most abundant leukocyte in peripheral blood (PB). Later on, others such as monocytes and lymphocytes arrive at the injured tissue to exert function. Every blood cell lineage is endowed with specific mechanisms and molecules to achieve recruitment; however, some parallelisms among these leukocytes can also be made. Migration relies on chemokine receptors, adhesion molecules, and the cytoskeleton connected to the outside portion of the leukocyte by adaptor proteins in the cytoplasm. The cytoskeleton is a biopolymer network composed of actin, microtubules, and intermediate filaments. All these polymers work in conjunction to deform a leukocyte and any other cell to recognize and respond to a stimulus dynamically. During an immune response, leukocyte recruitment occurs; however, mechanisms such as mature leukocyte intravasation from the bone marrow (BM) to PB also occur. Antigen-presenting cells (APCs) perform intravasation from inflamed tissues to lymphatic circulation to arrive at the lymph nodes (LNs). Moreover, homing to the LN by lymphoid cells occurs, and inside these organs, all these cells follow chemokine gradients to interact with each other. Strikingly, even platelets can exert migration; their interaction with other leukocytes is essential for proper movement. Finally, when the harmful agent disappears, the damaged tissue produces antiinflammatory mediators to turn off the immune response. Even at this stage, leukocyte movement is modulated to shut down the immune response. This chapter will review how leukocytes during immune responses traffic to different tissues as well as the general mechanisms these cells employ during these processes. After reading this chapter, the reader should be able to understand: (1) the general mechanisms leukocytes employ to exert movement; (2) the different steps of the leukocyte extravasation cascade; (3) that leukocyte movement in primary and secondary lymphoid organs (SLOs) is fundamental for responding to harmful agents; and (4) the general mechanisms to inhibit leukocyte movement during the resolution of inflammation.