First Aid, Chapter 1 Immune Mechanisms, Cell Adhesion Molecules Flashcards by Geeta Bhargave

What are the 4 classes of adhesion molecules?

Chemokines
Selectins
Integrins
Immunoglobulin superfamily

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What is the function of cell adhesion molecules?

Think of cell adhesion molecules (CAMs) as traffic cops: they aid in directing the traffic of leukocytes to areas of inflammation.

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What are the 4 families of chemokines that are most important to know?

C
CC
CXC
CX3

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What are the leukocytes associated with the “CC” family of chemokines? What do they trigger?

Eo’s, Baso’s, Mono’s

Involved in Allergy

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What are the leukocytes associated with the CXC family of chemokines? What do they trigger? What are the 2 different functions?

PMN’s
Inflammation
-ELR - angiogenic, acts through CXCR2
-Non-ELR - angiostatic, acts via CXCR3B, induced by interferons

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What is the homeostatic chemokine/receptor interaction? What is the action?

CCL19/CCL21 → CCR7 → Lymphocyte Homing

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What is the inflammatory chemokine/receptor interaction? What is the action?

CCL17/CCL22 → CCR4 → pro Th2 response

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What kind of receptors do chemokines signal through?

G protein-coupled receptors

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What pathways do chemokines trigger via G-protein coupled receptors?

Chemokines -> G-protein-coupled receptors -> PLC activation -> increase Ca2+
Chemokines -> G-protein-coupled receptors->MAP kinase activation -> ERK, JNK, or p38

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What are the receptors for CCL5 (RANTES?

CCR 1,3,5

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What is the ligand for CCR 1,3,5?

CCL5 (RANTES)

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What is the receptor for CCL11 (Eotaxin)?

CCR3

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What is the ligand for CCR3?

CCL11 (Eotaxin)

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What is the receptor for CCL17 (TARC)?

CCR4

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What is the ligand for CCR4?

CCL17 (TARC)

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What is the receptor for CXCL8 (IL-8)?

CXCR 1,2

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What is the ligand for CXCR 1,2?

CXCL8 (IL-8)

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What does RANTES stand for?

regulated on activation, normal T expressed and secreted

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What does TARC stand for?

thymus and activation-regulated cytokine

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What are some decoy chemokine receptors?

DARC (duffy), D6, CCX-CKR

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What is the clinical significant of DARC? What is the clinical significance of mutations in DARC?

Protects against metastasis; mutation in GATA in DARC gene confers malaria protection in African Americans.

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What is CCX-CKR a target for?

Target for CCL19 and CCL21

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In LAD-2, what are PMNs unable to express?

Carbohydrate ligands for E and P selectin.

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What are the locations of P Selectin (CD62P)

Platelets, and Weibel-Palade bodies of the endothelium

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What is the ligand for P selectin?

PGSL and Sialyl-Lewis X

What is the function of P selectin?

Binds PMNs, T lymphocytes, and monocytes

What is the location of E Selectin (ELAM endothelial leukocyte adhesion molecule and CD62E) ?

Endothelium

What is the ligand for E Selectin?

ESL-1, CD15, PGSL, and SialylLewis X

What is the function of E selectin?

Homing of T lymphocytes to peripheral sites of inflammation

What is the location of L Selectin (LAM-1 and CD62L)?

Lymphocytes and leukocytes

What is the ligand of L Selectin?

GLYCAM-1, MADCAM-1, CD34, and Sialyl-Lewis X

What is the funciton of L selectin?

Homing to lymph node HEV (GLYCAM) and PMN rolling (MAdCAM)

What selectin is increased in Kawasaki's Disease?

ELAM (Endothelial leukocyte adhesion molecule)

What is the function of selectins? What do they bind to?

All three types of selectins are involved in the rolling of leukocytes, and they bind carbohydrates.

What is the function of integrins?

All integrins are involved in adhesive interplay between APCs and lymphocytes as well as lymphocyte homing.

What are the three families of integrins?

B1, B2, B3

What is the name of the B1 integrin? What is its synonym?

A4B1 or VLA4

What is the ligand for A4B1 or VLA4 integrin?

VCAM

What is the function of A4B1 or VLA4 integrin?

Important for neuronal homing; used as treatment for multiple sclerosis

What are the other names of LFA1?

AlB2 or CD11a/CD18

What is the ligand of AlB2 (LFA1)?

ICAM-1

What is the function of AlB2 (LFA1)?

Rhinovirus binds here

What is another name for AmB2?

MAC1, CD11b/CD18

What is the ligand for AmB2?

ICAM-1, iC3B (CR3)

What is another name for AxB2?

CD11c/CD18

What is the ligand for AxB2?

ICAM3, C3dg, iC3B (CR4)

What is the function of AvB3 integrin?

Important for platelets and GIIBIIIa.

What does a4B7 bind to and what is its function?

The fourth β integrins family, α4β7 is also important. This family is a mucosal addressin that binds to mucosal addressin cell adhesion molecule (MAdCAM) and it is important for gut homing.

What are the immunoglobulin superfamily molecules involved in cell trafficking?

ICAM1 (CD54), ICAM2 (CD102), ICAM3 (CD50), ICAM4 (CD242), VCAM1 (CD106), PECAM (CD31), MadCAM, NCAM (CD56)

What is the other name for CD54? What does it bind?

ICAM1 (CD54) → binds LFA1, MAC1, and rhinovirus

What is the other name for CD102? What does it bind?

ICAM2 (CD102) → binds LFA1

What is the other name for CD50? What does it bind?

ICAM3 (CD50) → binds LFA1 and CD18

What is the other name for CD242? What does it bind?

ICAM4 (CD242) → binds LFA1 and CD18

What is the other name for CD106? What does it bind? What type of tissue is involved?

VCAM1 (CD106) → binds VLA4 (α4β1); vascular

What is the other name for CD31? What does it bind? What type of cells are involved?

PECAM (CD31) → binds CD31 and CD38; platelets

What does MadCAM bind?

MAdCAM → binds mucosal addressin (α4β7); mucosa

What is the other name for CD56? What does it bind to? What type of cell is involved?

NCAM (CD56) → binds VLA4 (α4β1); neuronal

What chemokine is associated with heparin induced thrombocytopenia?

CXCL4

What chemokines are associated with asthma and allergies?

CCL2, 5, 7, 11; CXCL8

How does a homozygous CCR5 mutation affect HIV?

Homozygotes - no infection

How does a heterozygote CCR5 mutation affect HIV?

slow progressors of infection

How does a mutation in CXCR4 affect HIV?

T trophic

How does a CCL3L1 mutation infection HIV?

Low level -> higher HIV acquisition, high viral load, worse disease

What chemokine defects are involved in atherosclerosis?

CXC3CL1, CX3CR1

How does a V249I mutation in CX3CR1 affect atherosclerosis (also known as fractalkine)?

V2491 -> increased risk of acute coronary syndrome

How does a V280M mutation in CX3CR1 affect atherosclerosis (also known as fractalkine)?

T280M→ Prevents plaque entry (confers protection)

What does GIIbIIIa defect lead to?

platelet defect in Glanzmann's thromasthenia

First Aid, Chapter 1 Immune Mechanisms, Cell Adhesion Molecules Flashcards

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