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Immunology > Leukocyte Adhesion and Circulation > Flashcards

Leukocyte Adhesion and Circulation Flashcards

1
Q

Name the 3 major selectins.

A

P-selectin (CD62P)
E-selectin (CD62E)
L-selectin (CD62L)

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2
Q

Where is P-selectin expressed?

A

Endothelium activated by histamine or thrombin

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3
Q

What is the ligand for P-selectin?

A

Sialyl Lewis X on P-selectin glycoprotein ligand 1 (PSGL-1) and other glycoproteins on neutrophils, monocytes, and T cells (effector, memory)

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4
Q

Where is E-selectin expressed?

A

Endothelium activated by microbial products (LPS) and/or cytokines (TNF, IL-1) produced by dendritic cells and macrophages

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5
Q

What is the ligand for E-selectin?

A

Sialyl Lewis X (e.g. cutaneous leukocyte antigen 1 (CLA-1)) on glycoproteins on neutrophils, monocytes, and T cells (effector, memory)

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6
Q

Where is L-selectin expressed?

A

Neutrophils, monocytes, T cells (naive and central memory), and B cells (naive)

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7
Q

What is the ligand for L-selectin?

A

Sialyl Lewis X on GlyCAM-1, CD34, MadCAM-1 (sialomucins) on endothelium (HEV), which are collectively called peripheral node addressin (PNAd)

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8
Q

What are lectins?

A

Carbohydrate-binding proteins

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9
Q

Name 4 major integrins.

A

1.Leukocyte function-associated antigen, LFA-1 (CD11aCD18)
2. MAC-1 (CD11bCD18, CR3)
3. Very late antigen 4, VLA-4 (CD49aCD29)
4. a4B7 (CD49dCD29)

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10
Q

What is/are the ligand(s) for LFA-1 (CD11aCD18)?

A

ICAM-1 (intercellular adhesion molecule) and ICAM-2 on endothelium

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11
Q

What is/are the ligand(s) for MAC-1 (CD11bCD18)?

A

ICAM-1 and ICAM-2 on endothelium

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12
Q

What is/are the ligand(s) for VLA-4 (CD49aCD29)?

A

VCAM-1

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13
Q

What is/are the ligand(s) for a4B7?

A

VCAM-1 and MadCAM-1 on endothelium in gut and gut-associated lymphoid tissues

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14
Q

What are selectins?

A

Carbohydrate-binding protein adhesion molecules

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15
Q

What are selectin ligands?

A

Sialylated and fucosylated carbohydrate groups of Lewis X and Lewis A family present on glycoproteins of various cells

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16
Q

What is the structure of integrins?

A

Heterodimeric proteins that contain an alpha chain and a beta chain

Extracellular head binds to ligands and intracellular domain interacts with cytoskeletal components like actin, tropomysin
Initiate interactions with cytoskeleton through G-protein coupled receptors

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17
Q

What are chemokines?

A

Chemotactic cytokines that regulate movement of leukocytes

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18
Q

How are chemokines named?

A

Based on cysteine residues

C family: single cysteine residue
CC family: 2 adjoining cysteine residues (beta chemokines)
CXC family: 2 cysteine residues separated by one amino acid (alpha chemokines)
CX3C: 2 cysteine residues separated by three amino acids

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19
Q

Name key chemokines involved in mixed leukocyte recruitment

A

CCL2 and CCL3

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20
Q

Name key chemokines involved in allergic processes

A

CCL5 (RANTES): Mixed leukocyte recruitment
CCL11 (Eotaxin): Eosinophil, basophil and Th2 recruitment
CCL17 (TARC): T cell recruitment

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21
Q

Name two chemokines important for T cell and dendritic cell migration into parafollicular zones of lymph nodes. Which receptor do they bind?

A

CCL19, CCL21, which bind CCR7

22
Q

Name a chemokine important for neutrophil recruitment. Which receptors do they bind?

A

CXCL8 (IL-8), which binds CXCR1 and CXCR2 on neutrophils

23
Q

Which chemokine is important for B cell migration into lymph nodes? Which receptor does it bind?

A

CXCL13, which binds CCR5

24
Q

How do chemokines affect integrins?

A
  1. Induce membrane clustering
  2. Increase affinity for integrin receptors
25
Q

What are the 6 steps of leukocyte recruitment into a site of inflammation?

A
  1. Tissue infection or injury
  2. Rolling
  3. Increase in integrin affinity
  4. Adhesion
  5. Migration through the endothelium
  6. Migration of leukocytes to site of infection and tissue injury
26
Q

What is the cause of LAD type 1?

A

Defect in CD18, B subunit of integrin ligands LFA-1 (aLB2 = CD11aCD18) and Mac-1 (aMB2 = CD11bCD18)

27
Q

What is the cause of LAD type 2?

A

Lack of Golgi fucose transporter needed to express carbohydrates (sLeX) on E and P selectin ligands on neutrophils

28
Q

What is the cause of LAD type 3?

A

Defect in signaling pathway linking chemokine receptor to integrin activation (Kindlin 3)

29
Q

Name a chemokine receptor that mediates monocyte migration to sites of infection/injury. Which chemokine(s) does it bind?

A

CCR2 binds CCL2, MCP-1

30
Q

Name chemokine receptor(s) that mediate neutrophil migration to sites of infection/injury. Which chemokine(s) does it bind?

A

CXCR1, CXCR2 bind CXCL8 (IL-18) produced by macrophages

31
Q

Which cytokine is important for development of high endothelial venules?

A

Lymphotoxin

32
Q

What is the role of L-selectin on T cells?

A

Expressed on naive T cells
Binds selectin ligands on high endothelial venules (HEV), peripheral node addressins (PNAd)

33
Q

Give two examples of peripheral node addressins (PNAd). Where are they expressed?

A
  1. GlyCAM-1, which is expressed on high endothelial venules of lymph nodes
  2. MadCAM-1, which is expressed in Peyer’s patches
34
Q

What do peripheral node addressins (PNAd) bind?

A

L-selectin on naive T cells

35
Q

Which integrin on T cells mediates firm adhesion of naive T cells to high endothelial venules of lymph nodes?

A

LFA-1 (lymphocyte function-associated antigen 1)

36
Q

Which chemokine(s) activate naive T cell integrins to a high affinity state? Which receptor do they bind?

A

CCL19 and CCL21, which bind CCR7

37
Q

Where is there a high concentration of sphingosine 1 phosphate (S1P)?

A

Blood and lymph

38
Q

Where is there a low concentration of sphingosine 1 phosphate (S1P)?

A

Tissues

39
Q

Describe the mechanism by which activated T cells are retained in the lymph nodes.

A

Activated T cells express CD69 (IFN type 1) that binds the S1P receptor 1 (S1PR1), causing them to become insensitive to the S1P gradient.

40
Q

Describe the mechanism by which effector T cells exit the lymph node.

A

After differentiation into effector cells, T cells lose CD69, re-express S1PR1 and exit the lymph node

41
Q

Describe the mechanism of action of fingolimod.

A

Binds S1PR1 and causes T cells to remain in lymph nodes

42
Q

Where is MadCAM-1 expressed? What does it bind?

A

Mucosal addressin cell adhesion molecule 1 (MadCAM-1) binds:
1. L-selectin on T cells
2. Integrin alpha4beta7 on T cells

43
Q

Which molecules involved in naive T cell circulation are down-regulated by effector T cells?

A

CCR7 and L-selectin

44
Q

Which selectin ligand is important for homing to the skin?

A

Cutaneous lymphocyte antigen (CLA) binds E-selection on endothelial cells in the skin

45
Q

What is the mechanism of action of vedolizumab?

A

Anti-alpha4beta7, to prevent homing of T cells to the gut

46
Q

Which molecules are expressed on central and effector memory T cells?

A

Central memory T cells: high CD45RO, high CCR7, high L-selectin
Effector memory T cells: high CD45RO, low CCR7, low L-selectin

CCR7 and L-selectin mediate homing to secondary lymphoid organs (SLO)

47
Q

Which molecule(s) are important for migration of B lymphocytes into the spleen?

A

CXCR5 on B cells binds CXCL13 on white pulp

48
Q

Which molecule(s) are important for migration of B lymphocytes into the lymph nodes?

A

To enter lymph node:
CXCR4 binds CXCL12
CCR7 binds CCL19 and CCL21

To enter follicle:
CXCR5 binds CXCL13 produced by follicular dendritic cells

49
Q

Which molecule(s) are important for migration of B lymphocytes into Peyer’s patches?

A

CXCR5 binds CXCL13
Integrin alpha4beta7 binds MadCAM1

50
Q
A

Immunology (10 decks)

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