Adhesion Molecules

Front 1

Leukocyte trafficking:
1. Activation of leukocyte integrins via chemokines, and firm binding
2. Act of crossing the endothelium using adhesion molecules
3. Following leukocyte margination, upregulation of binding using selectins
4. Once in the tissue, Leukocytes move toward the initial inflammatory stimulus

Back 1

1. Adhesion
2. Transmigration
3. Rolling
4. Chemotaxis

Front 2

1. What is a polarized lymphocyte?
2. What do the selectin lectin domains bind on target cells?
3. What modification do selecting glycoproteins have?

Back 2

1. One that is firmly adhered to the surface
2. Oligosaccharides
3. Sialylated or fucosylated

Front 3

1. What cell type is E selectin expressed on?
2. P selectin?
3. L selectin?

Back 3

1. Activated Endothelium
2. Activated Endothelium, platelets
3. Leukocytes

Front 4

1. What P Selectin ligand do PMN respond to?
P/E ligands include PSGL-1 (p selecting glycoprotein ligand) SLex (sialyl Lewis X)

2. What are 2 important ligands for L selectins?
Others: CD34, PSGL-1

Back 4

1. CD24
2. GlyCAM (glycosylation dependent cell adhesion molecule
3. MADCAM- mucosal addressin cell...

Front 5

Integrins have alpha and beta glycoprotein chains, they integrate the cytoskeleton with the ECM

Conformational changes alter presentation of the I domain and dictate affinity of integrin for its ligand. They can activate very fast

Back 5

Integrin family has alpha M B2, alpha L B2, alpha X B2, alphaD B2

Front 6

1. What does ICAM stand for, where is it expressed?
2. VCAM, where is it expressed?
3. PECAM where is it expressed
4. LEEPCAM

Back 6

1. Intercellular adhesion molecule; endothelium only
2. Vascular cell adhesion mol, endothelium only
3. Platelet endothelial cell ... Leuko & endo
4. Lymphocyte endothelial and epithelial cell adhesion, on skin

Front 7

1. Integrin Ca2+ independent cell adhesion is known as what?

Integrins serve as counterreceptors for leukocyte integrins during adhesion to the endothelium

Back 7

1. Homotypic (bind to themselves, PECAM-1) cell-cell adhesion

Front 8

Give the EC ligand for following leukocyte receptors:
1. AlphaL - Beta2
2. AlphaM - Beta2
3. Alpha4 - Beta 1
4. Alpha4 - Beta 7
5. PECAM-1
6. CD99

Back 8

1. ICAM1, ICAM 2, JAM A
2. ICAM2, JAM3
3. VCAM-1
4. MadCAM
5. PECAM-1
6. CD99

Front 9

1. What CD marker fxns in lymphocyte adhesion to the endothelium as well as lymphocyte homing?
2. What is the major receptor of 1?

Back 9

1. CD44
2. Hyaluronic acid

Front 10

1. How many extracellular Ig domains do JAMs have? Junctional Adhesion Molecule
2. What 2 JAM have homophilic interactions?

CD99 is an O-glycosylated protein expressed by most leukocytes and endothelial cells
PECAM is part of Ig superfamily

Back 10

1. 2
2. CD99 and PECAM-1

Front 11

Name the leukocyte molecule and role
1. P-selectin
2. ICAM-1, ICAM-2
3. E-selectin
4. PECAM-1

Back 11

1. SLex, CD24, PSGL-1 (rolling)
2.alphaLBeta2 integrin, alphaMbeta2 integrins (Adhesion)
3. Slex, PSGL-1; Rolling (and adhesion)
4. PECAM-1; Transmigration

Front 12

Name the leukocyte molecule and role
1. PSGL-1
2. VCAM-1
3. CD99
4. JAM-B

Back 12

1. L-selectin (Rolling)
2.alphaMbeta2 integrin (adhesion)
3. CD99 (transmigration)
4. alpha4Beta1 integrin (transmigration)

Front 13

Name the leukocyte molecule and role
1. Glycam-1, CD34, MadCam
2. MadCam
3. Jam-A
4. Jam-c

Back 13

1. L-slectin - homing to HEV (high endothelial venule)
2. alpha4Beta7 integrin- homing to HEV
3. alphaLBeta2 integrin- transmigration
4. alphaMbeta2 integrin- transmigration

Front 14

1. How does margination occur?
2. What is P-selectin released from platelets in response to (2)?
3. What is E-selectin released from and in response to what?

Back 14

1. Alter EC surface, plus leakage pushes the leukocytes to the side of the vessel
2. Thrombin, Histamine- very rapid
3. Endothelial cells, IL-1 and LPS, TNF

Front 15

1. Which of the selectins is expressed first P or E, then what is expressed later?
2. Chemokines activate leukocyte integrins and recruit additional leukocyte integrins through membrane associated what?

Back 15

1. P then E (neutrophils), followed by adhesion molecules (monocytes and macrophages)
2. GPCR

Front 16

Name the target cell and associated disorder:
1. IL-8 & PAF
2. MCP-1,2,3 MIP-1alpha, Beta PAF
3. Eotaxin, PAF, IL-5
4. Lymphotaxin
5. IL-8, MIP-1alpha, MCP-1,3, RANTES

Back 16

1. Neutrophils, bronchopneumonia
2. Monocytes, Arteriosclerosis
3. Eosinophils, Asthma
4. Lymphocytes
5. Basophils

Front 17

Chemokines mediate basal lymphocyte homing
1. What is diapedesis?
2. What are the 2 possible routes for diapedesis?

Loss of Beta2 integrin in knockout mice reveal neutrophil defects,skin ulceration, dermatitis

Back 17

1. Crossing the basement membrane into the extracellular space
2. Paracellular (jxn between endothelial cells) or Transcellular (through the endothelium)

Front 18

1. What is it and what does it Leukocyte adhesion deficiency (LAD) type 1 lead to?

**Candidates for bone marrow transplant and gene therapy

Back 18

1. A mutation/absence in the beta2 integrin chain which prevents its association with alpha subunits L, M, X.
Delayed separation of umilical cord, periodontitis, infection of oral and genital mucosa, skin, intestine, respiratory

Front 19

1. Lifespan expectancy if NO CD18 (B2 chain)
2. If 1-10% CD18)?

Back 19

1. 1-10 yrs
2. 40 yrs

Front 20

1. What do patients lack in LAD II?
2. What sx does this cause

Back 20

1. problem in fucosylation, lack sialyl Lewis X (ligand for P and E selectins)
2. similar to LAD 1, but also growth retardation and neurologic defects

Front 21

1. What is Rac2?
2. Sx of deficiency?

**Neutrophilia in the blood at the location, b/c neutrophils headed to the area, but were unable to exit the blood stream. Also a shortage of pus in these cases

Back 21

1. Rac2 is a member of a family of proteins (GTPases) That are involved in regulating coordinated movements of the cytoskeleton (migration, phagocytosis, ROS production). Rac2 is the major one in neutrophils
2. Neutrophil chemotaxis, secretion of primary granules and defective generation of superoxide in response to formyl peptides are all impaired

Front 22

1. What is the problem in LAD III?
2. Sx?

**elevated leukocytes in all LAD deficiencies. Tumor cells begin expression selectins like leukocytes

Back 22

1. Defect in kindlin-2, an integrin co-receptor
2. Similar to LAD 1, but also severe bleeding, infection at an early age, integrins are expressed but fail to fxn

Front 23

Simply what steps of leukocyte migration do following interfere with?
1. LAD I
2. LAD II
3. Kindlin mutation
4. Rac 2

Back 23

1. Firm adhesion, integrins
2. Tethering and rolling, selectins
3. Firm adhesion
4. Transmigration