eukocyte migration chapter 15 and inflammation ANY TYPES OF LEUKOCYTES MOVE FROM ONE part of the body to another. This is espe cially true of lymphocytes, which circulate continually in the blood and lymph and, in common with other types of leukocytes, migrate into the tissues at sites of infection or tissue injury. This recirculation not only in creases the chance that lymphocytes specific for a particular antigen will encounter that antigen but also is critical to Lymphocytes Attached to the Surface of a High-Endothelial Venule development of an inflammatory response. Inflammation is a complex response to local injury or other trauma; it is characterized by redness, heat, swelling, and pain. Inflam- a Lymphocyte Recirculation mation involves various immune-system cells and numer- a Cell-Adhesion Molecules ous mediators. Assembling and regulating inflammatory responses would be impossible without the controlled Neutrophil Extravasation migration of leukocyte populations. This chapter covers the a Lymphocyte Extravasation molecules and processes that play a role in leukocyte migra- tion, various molecules that mediate inflammation, and the a Chemokines-Key Mediators of Inflammation characteristic physiologic changes that accompany inflam a Other Mediators of Inflammation matory responses a The Inflammatory Process Anti-Inflammatory Agents Lymphocyte Recirculation Lymphocytes are capable of a remarkable level of recircula on, continually moving through the blood and lymph to the various lymphoid organs(Figure 15-1). After a brief transit time of approximately 30 min in the bloodstream, and back again as often as 1-2 times per day. Since only directly to the spleen, where they reside for approximately gen, it would appear that a large number of T or B cells must 5 h Almost equal numbers(42%)of lymphocytes exit from contact antigen on a given antigen-presenting cell within a the blood into various peripheral lymph nodes, where they short time in order to generate a specific immune response reside for about 12 h. A smaller number of lymphocytes The odds of the small percentage of lymphocytes committed (10%)migrate to tertiary extralymphoid tissues by crossing to a given antigen actually making contact with that antigen between endothelial cells that line the capillaries. These tis- when it is present are elevated by the extensive recircula- sues normally have few, if any, lymphoid cells but can import tion of lymphocytes. The likelihood of such contacts is them during an inflammatory response. The most immuno- profoundly increased also by factors that regulate, organize, interface with the external environment, such as the skin presenting cells culation of lymphocytes and antigen logically active tertiary extralymphoid tissues are those that and direct the ci and various mucosal epithelia of the gastrointestinal, pul- monary, and genitourinary tracts The process of continual lymphocyte recirculation allows Cell-Adhesion molecules maximal numbers of antigenically committed lymphocytes to encounter antigen. an individual lymphocyte may make a The vascular endothelium serves as an important gate- omplete circuit from the blood to the tissues and lymph keeper, "regulating the movement of blood-borne molecules■ Lymphocyte Recirculation ■ Cell-Adhesion Molecules ■ Neutrophil Extravasation ■ Lymphocyte Extravasation ■ Chemokines—Key Mediators of Inflammation ■ Other Mediators of Inflammation ■ The Inflammatory Process ■ Anti-Inflammatory Agents Leukocyte Migration and Inflammation M       part of the body to another. This is espe￾cially true of lymphocytes, which circulate continually in the blood and lymph and, in common with other types of leukocytes, migrate into the tissues at sites of infection or tissue injury. This recirculation not only in￾creases the chance that lymphocytes specific for a particular antigen will encounter that antigen but also is critical to development of an inflammatory response. Inflammation is a complex response to local injury or other trauma; it is characterized by redness, heat, swelling, and pain. Inflam￾mation involves various immune-system cells and numer￾ous mediators. Assembling and regulating inflammatory responses would be impossible without the controlled migration of leukocyte populations. This chapter covers the molecules and processes that play a role in leukocyte migra￾tion, various molecules that mediate inflammation, and the characteristic physiologic changes that accompany inflam￾matory responses. Lymphocyte Recirculation Lymphocytes are capable of a remarkable level of recircula￾tion, continually moving through the blood and lymph to the various lymphoid organs (Figure 15-1). After a brief transit time of approximately 30 min in the bloodstream, nearly 45% of all lymphocytes are carried from the blood directly to the spleen, where they reside for approximately 5 h. Almost equal numbers (42%) of lymphocytes exit from the blood into various peripheral lymph nodes, where they reside for about 12 h. A smaller number of lymphocytes (10%) migrate to tertiary extralymphoid tissues by crossing between endothelial cells that line the capillaries. These tis￾sues normally have few, if any, lymphoid cells but can import them during an inflammatory response. The most immuno￾logically active tertiary extralymphoid tissues are those that interface with the external environment, such as the skin and various mucosal epithelia of the gastrointestinal, pul￾monary, and genitourinary tracts. The process of continual lymphocyte recirculation allows maximal numbers of antigenically committed lymphocytes to encounter antigen. An individual lymphocyte may make a complete circuit from the blood to the tissues and lymph and back again as often as 1–2 times per day. Since only about one in 105 lymphocytes recognizes a particular anti￾gen, it would appear that a large number of T or B cells must contact antigen on a given antigen-presenting cell within a short time in order to generate a specific immune response. The odds of the small percentage of lymphocytes committed to a given antigen actually making contact with that antigen when it is present are elevated by the extensive recircula￾tion of lymphocytes. The likelihood of such contacts is profoundly increased also by factors that regulate, organize, and direct the circulation of lymphocytes and antigen￾presenting cells. Cell-Adhesion Molecules The vascular endothelium serves as an important “gate￾keeper,” regulating the movement of blood-borne molecules chapter 15 FPO Lymphocytes Attached to the Surface of a High-Endothelial Venule