Advanced Immunology

Question 1

Where are almost all hematopoietic cells found?

Answer 1

In the blood (recirculation)

Question 2

Location and migration of lymphocytes is important for… (4)

Answer 2

• Homing to organs or tissues
• Homing to compartments
• Cell cell interactions
• Exit from compartments/organs

Question 3

What can be said about the kind of expression and what they attract if you talk about inflammatory chemokines?

Answer 3

• Induced expression
• Attract activated lymphocytes

Question 4

What can be said about the kind of expression and what they attract if you talk about homeostatic chemokines?

Answer 4

• Constitutive expression in lymphoid organs
• Attract naive T/B/DCs

Question 5

What are the mechanisms of attraction of leukocytes? (3)

Answer 5

• Chemotaxis
• Haptotaxis
• Chemo- or haptokinesis

Question 6

Mechanisms of attraction of leukocytes: describe chemotaxis

Answer 6

Migration with a soluble gradient

Question 7

Mechanisms of attraction of leukocytes: describe haptotaxis

Answer 7

Migration with a bound gradient

Question 8

Mechanisms of attraction of leukocytes: describe chemo- or haptokinesis

Answer 8

Migration without a gradient

Question 9

Which factors regulate cell migration? What do they attract?

Answer 9

• Chemokines
• Attract cells expressing the appropriate receptor

Question 10

Which factors regulate adhesion of leukocytes? What are their ligands?

Answer 10

• Integrins
• Ligands: extracellular matrix proteins

Question 11

What do integrins bind to?

Answer 11

Extracellular matrix and counter ligands

Question 12

What are examples of other ligands for integrins?

Answer 12

VCAM-1, MadCAM-1, ICAM-1,2,3

Question 13

Where do lymphocytes enter the lymph nodes?

Answer 13

At specialized blood vessels, called high endothelial venule (HEV)

Question 14

What are high endothelial venules? What do they allow for?

Answer 14

• Specialized form of postcapillary blood vessel
• Allows for extravasation of cells

Question 15

Where are HEVs found?

Answer 15

In T cell zones of LNs and PP

Question 16

What can be said about the extravasation in resting lymph nodes?

Answer 16

Constitutive extravasation of naive T- and B lymphocytes

Question 17

What are the steps of lymphocyte extravasation? (5)

Answer 17

• Rolling and tethering
• Sticking
• Crawling
• Transmigration
• Exit ramp/Accumulation in an HEV pocket

Question 18

What induces rolling of lymphocytes in HEVs? What are they made by?

Answer 18

• Expression of specific sugars on the endothelial cells in the LN
• Made by enzymes

Question 19

Which two enzymes are specific for endothelial cells? What does that imply?

Answer 19

• GlcNAc6ST2 and FUT7
• They make sugar structures that are unique for endothelial cells

Question 20

Which molecule on leukocytes can specifically bind to the sugar structures on the endothelial cells?

Answer 20

L-selectin

Question 21

What can be said about the binding between L-selectin and the sugar structures on the endothelial cells?

Answer 21

• Not a very high affinity binding
  –> binding/release
• Induces rolling along the endothelium

Question 22

What causes sticking/full arrest of the leukocyte? Which two ways are there?

Answer 22

Chemokine-mediated activation of integrins:
- Inside-out signaling
- Outside-in signaling

Question 23

What is integrin activation by inside-out signaling?

Answer 23

Chemokine receptor signaling changes integrin configuration:
- CCR7-CCL21 interaction causes a change in LFA-1 conformation on the T cell

Question 24

What is integrin activation by outside-in signaling?

Answer 24

Integrins on leukocytes bind to integrin receptors on HEV –> high affinity:
- LFA-1 (after a conformational change) on T cells binds to ICAM-1 on HEVs

Question 25

What cells synthesize S1P?

Answer 25

Endothelial cells and red blood cells. This makes S1P concentration high in bodily fluids and low in tissues, creating a gradient for T cells to follow.

Question 26

What homeostatic chemokines attract B cells and T cells, respectively, and what cells produce them and where?

Answer 26

• CXCL13 is expressed by stromal cells in the B cell follicles.
• CCL21 is produced by stromal cells in the paracortex and promotes T cell and dendritic cell migration.

Question 27

What is more common, chemotaxis or haptotaxis?

Answer 27

Haptotaxis