Chapter 3 Leukocyte Circulation and Migration into Tissues pgs 37-43

Question 1

Why does the immune system move its cellular components into the tissues? What structures? (3)

Answer 1

1) Delivery of leukocytes
2) Delivery of lymphocytes
3) Delivery of effector lymphocytes

Question 2

Adhesion of circulating leukocytes to vascular endothelial cells is mediated by two classes of molecules. What are those two classes of molecules called?

Answer 2

Selectins and integrins.

Question 3

Selectins

Answer 3

plasma membrane carbohydrate-binding adhesion molecules that mediate an initial step of low-affinity adhesion of circulating leukocytes to endothelial cells lining post-capillary venules. (expressed on leukocytes and endothelial)

Question 4

E- selectin

Answer 4

(CD62E) Expressed on the endothelial cell surface within 1 to 2 hours in response to the cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF) TNF and IL-1 produced by tissue macrophages in response to infection.

Question 5

Sialylated Lewis X

Answer 5

Ligands on leukocytes that bind to E-selectin and P-selectin on endothelial cells.

Question 6

L-Selectin

Answer 6

(CD62L) expressed on leukocytes and not on endothelial cells. ligands are sialomucins on endothelial cells.

Question 7

Integrins

Answer 7

cell surface proteins that mediate adhesion of cells to other cells or to extracellular matrix, through specific binding interaction with various ligands.

Question 8

LFA-1

Answer 8

(Leukocyte function associated antigen 1) integrin associated with leukocytes responsible for adhesion to endothelial cells, lymphocytes, dendritic cells, macrophages, fibroblasts, and keratinocytes.

Question 9

ICAM-1

Answer 9

ligand for LFA-1. Intracellular adhesion molecule-1 a membrane glycoprotein expressed on cytokine-activated endothelial cells, lymphocytes, dendritic cells, macrophages, fibroblasts, and keratinocytes.

Question 10

Integrin activation

Answer 10

the process by which integrins respond to intracellular signals by rapidly increasing their affinity for ligands. Occurs in all leukocytes in response to chemokine binding to chemokine receptor, and in T cells when antigen binds to antigen receptors. Leads to increased affinity for receptors on endothelial cells.

Question 11

Avidity

Answer 11

Extreme eagerness or enthusiasm. The overall strength of binding between an antigen and an antibody.

Question 12

Leukocyte recruitment from blood into tissues is regulated by the action of what molecule?

Answer 12

Chemokines specifically CXCL8

Question 13

What are the two roles that cytokines play in inflammation?

Answer 13

1) Increased adhesion of leukocytes to endothelium (signals from chemokine receptors lead to increased integrin affinity)
2) Migration of leukocytes to site of infection or tissue damage. (Via Chemokinesis)

Question 14

CXCR8

Answer 14

Chemokine Receptors: CXCR1, CXCR2; Major function, Neutrophil recruitment

Question 15

What sequence of events leads to leukocytes migrating into tissues?

Answer 15

1) Selectin-mediated rolling of leukocytes on endothellium (rolling occurs due to low affinity Kd of ligand to selectin receptors. They continually bind, roll, and bind);
2) Chemokine-mediated increase in affinity of integrins:(Chemokines displayed on endothelial surfaces increase affinity of leukocytes)
3) Stable integrin-mediated adhesion of leukocytes to endothelium: ICAM-1 binds to LFA-1 causing firm attachement to the endothelium.;
4) Transmigration of leukocytes through the endothelium

Question 16

Margination

Answer 16

The process by which leukocytes flow toward the lining of of vessels. This occurs, because leukocytes are much larger than rbcs, so they move away toward the central axis of flow.

Question 17

Paracellular Transmigration

Answer 17

The process by which leukocytes transmigrate between the borders of endothelial cells to reach extravascular tissues.

Question 18

What leukocytes are recruited to sites of infection and injury? How are they recruited there?

Answer 18

1) Neutrophils and monocytes are recruited to tissue sites of infection and injury; 2) they are recruited via a selectin, integrin, and chemokine-dependent multistep process