Leukocyte Migration into Tissues

ADHESION MOLECULES ON LEUKOCYTES AND ENDOTHELIAL CELLS INVOLVED IN LEUKOCYTE RECRUITMENT, 39

Selectins and Selectin Ligands, 39 Integrins and Integrin Ligands, 40

CHEMOKINES AND CHEMOKINE RECEPTORS, 41

Chemokine Structure, Production, and Receptors, 41 Biologic Actions of Chemokines, 43

LEUKOCYTE-ENDOTHELIAL INTERACTIONS AND LEUKOCYTE EXTRAVASATION, 43

MIGRATION OF NEUTROPHILS AND MONOCYTES TO SITES OF INFECTION OR TISSUE INJURY, 45

MIGRATION AND RECIRCULATION OF T LYMPHOCYTES, 45

Recirculation of Naive T Lymphocytes between Blood and Secondary Lymphoid Organs, 46 Recirculation of T Cells through Other Lymphoid Tissues, 49 Migration of Effector T Lymphocytes to Sites of Infection, 50 Memory T Cell Migration, 51

MIGRATION OF B LYMPHOCYTES, 51

SUMMARY, 52

A unique property of the immune system that distinguishes it from all other tissue systems in the body is the constant and highly regulated movement of its major cellular components through the blood, into tissues, and often back into the blood again. This movement accomplishes three main functions (Fig. 3-1):

• Delivery of leukocytes of myeloid lineage (mainly neutrophils and monocytes) from their bone marrow site of maturation into tissue sites of infection or injury, where the cells perform their protective functions of eliminating infectious pathogens, clearing dead tissues, and repairing the damage.

• Delivery of lymphocytes from their sites of maturation (bone marrow or thymus) to secondary lymphoid organs, where they encounter antigens and differentiate into effector lymphocytes.

• Delivery of effector lymphocytes from the secondary lymphoid organs in which they were produced to sites of infection in any tissue, where they perform their protective functions.

The migration of a particular type of leukocyte into a restricted type of tissue, or a tissue with an ongoing infection or injury, is often called leukocyte homing, and the general process of leukocyte movement from blood into tissues is called recruitment. The migration of leukocytes to tissues follows several general principles.

• Leukocytes that have not been activated by external stimuli (i.e., are considered to be in a resting state) are normally located in the circulation and lymphoid organs. Only after activation are these cells rapidly recruited to where they are needed. The activating stimuli typically are products of microbes and dead cells (during innate immune responses) and antigens (during adaptive immune responses).

• Endothelial cells at sites of infection and tissue injury are also activated, mostly in response to cytokines secreted by macrophages and other tissue cells at these sites. Endothelial activation results in increased adhesiveness of endothelial cells for circulating leukocytes; the molecular basis of this adhesiveness is described later.

• The recruitment of leukocytes and plasma proteins from the blood to sites of infection and tissue injury is called inflammation. Inflammation is triggered by recognition of microbes and dead tissues in innate immune responses and is refined and prolonged during adaptive immune responses. This process delivers the cells and molecules of host defense to the sites where offending agents need to be combated. The same process is responsible for causing tissue damage and underlies many important diseases. We will return to inflammation in the context of innate immunity in Chapter 4 and in the discussion of inflammatory diseases in Chapter 18.

Postcapillary venule

Infected or injured tissue

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