White Blood Cells (Leukocytes)

White blood cells or "leukocytes" combat infection and in some cases phagocytose and digest debris. White blood cells are traditionally grouped into three major categories based on their appearance in the light microscope. These classes are the 1) lymphocytes, 2) granulocytes and 3) monocytes. Out of all the leukocytes, only lymphocytes possess the attributes of specificity, memory and self/nonself recognition. All the other leukoctyes play accessory roles, serving to activate lymphocytes, to increase the effectiveness of antigen clearance by phagocytosis, or to secret various immune effector molecules.

New leukocytes enter the blood from the bone marrow (innate immune cells and B cells) or thymus (naive T cells) and express characteristic trafficking molecule patterns that enable and restrict their migration to certain regions.

Leukocyte Migration:

Leukocytes circulate into inflammed tissues and peripheral lymphoid organs by passing between endothelial cells lining the walls of blood vessels (diapedesis). Leukocytes possess receptors which bind to leukocytes-specific cell adhesion molecules (CAMS) on endothelial cells in this extravasation mechanism. Some of these CAMS are expressed constitutively whereas others are expressed in response to localized concentrations of cytokines produced during an inflammatory response.  Most CAMS belong to the following 4 families of proteins:

• Integrins;
• Selectins
• mucins are a group of serine and threonine rich proteins that are heavily glycosylated.
• ICAMs contain a variable number of immunoglobulin like domains and thus are classified in the immunoglobulin superfamily.

Selectins and mucin-like CAMs interact with each other, and members of each family are expressed on both leukocytes and endothelial cells. Integrins which are expressed on leukocytes, interact with ICAMS expressed on endothelial cells.

As an example of CAM function, activated endothelial cells express adhesion molecules of the selectin family which interact with mucin-like cell-adhesion molecules on the neutrophil membrane. As Neutrophils roll over the endothelial cells, they are activated by various chemoatractants like chemokines and platelet activating factor (PAF) which triggers an activating signal mediated by G proteins associated with receptors on the neutrophil membrane This signal induces a conformational change in the integrin molecules in the neutrophil membrane, increasing their affinity for the Ig-super family adhesion molecules on the endothelium.