13 Cellular Immunity 1

Question 1

What are the 4 amino acid patterns of chemokines?

Answer 1

• CC
• CXC
• CX3C
• C or XC (lack 1st conserved cysteine)

Question 2

T/F chemokines produce an intracellular signal?

Answer 2

False. (ish) Only the heterotrimeric G protein they are bound to produces the signal.

Question 3

How many chemokine receptors are there? All of these have how many transmembrane domains in their accompanying G-protein?

Answer 3

• 18

- 7

Question 4

What is the nomenclature for naming chemokines and receptors?

Answer 4

• CCL1- ligand

- CCR1- Receptor

Question 5

Which cells can extravasate into lymph nodes through HEV’s? (high endothelial venules)

Answer 5

lymphocytes only (the rest all use lymphatics to get there)

Question 6

Which important surfaces are the following molecules located on?
-L-selectin, P-selectin, E-selectin, CCL21, CXL12, LFA1, integrins

Answer 6

Endothelial cells: E and P selectin
Platelets: P selectin
Lymphocytes: L selectin, CCL21, CXL12, LFA-1 (an integrin)

Question 7

Which selectins are constitutive and which are induced by inflammation?

Answer 7

• L is constitutueve

- E and P are inducible on blood vessel endothelium (and are constitutive in other body areas)

Question 8

What are the “Other” surfaces where the 3 selectins are expressed? (may be unimportant?)

Answer 8

• L: myeloid cells (constitutive)
• E: skin endothelium (constitutive)
• P: choroid plexus, lung endothelium (constitutive)

Question 9

What do selectins bind to?

Answer 9

carbohydrate structures. (which are usually on membrane-bound mucin proteins)

Question 10

What molecule links a carb to a protein?

Answer 10

O linked carbohydrates (ser and thr)

Question 11

What are integrins made up of?

Answer 11

alpha and beta chain (24 combinations of 8 dif beta and 18 dif alpha chains)

Question 12

What activates an integrin? What does that accomplish? What is

Answer 12

• stimulation of TCR or chemokine receptor

- makes it extra sticky

Question 13

LFA-1 integrin binds to what?

Answer 13

ICAM-1

Question 14

Describe the process of interactions that results in leukocyte rolling and stopping?

Answer 14

From the lymphocyte’s side of the story:

• L-selectin (a receptor) binds GlyCAM-1, CD34, PNAd, or MAdCAM-1 (Rolling).
• CCR7 binds CCL19 or CCL21. This signals…
• Integrin (LFA-1 for ex.) conformational change
• Tight binding (of LFA-1) to ICAM-1

Question 15

What molecule signals naive T cells to exit lymph nodes? Where is it mainly present in the body?What is its receptor? What happens then?

Answer 15

• S1P
• Blood (Highest) and lymph (lower)
• G-protein coupled receptor called S1P1
• once it binds this receptor, it migrates toward the signal, into the blood. Once here, the receptor is down-regulated so that lymphocytes can leave the blood again into another lymph node. If it enters a lymph tissue where S1P is low, then expression of the receptor “recovers” and goes up again.

Question 16

What keeps S1P low in lymphoid and peripheral tissues?

Answer 16

S1P lyase

Question 17

What directs Dendritic Cells to peripheral tissues?

Answer 17

Chemokine receptors

Question 18

What directs Dendritic Cells to lymph nodes?

Answer 18

-Once activated by Ag+ TLR’s (Toll-like Receptors), DC’s upregulate CCR7 and follow the same CCL19/CCL21 gradient that lymphocytes use to “activate” their integrins (note the lymphocyte process occurs in blood vessels!)

Question 19

Approximate amount of antigen-specific naive CD 8 and CD 4 cells?

Answer 19

• CD 8: 80-1,200

- CD4: 15-200

Question 20

What is priming?

Answer 20

-activation of naive T cells following encounter w/ Ag

Question 21

IL-2 binds what receptor? Which chain of that receptor is expressed first following priming? What function does IL-2 binding have?

Answer 21

• CD25
• alpha chain
• Drives clonal expansion, esp. of Th1 cells

Question 22

What is the main molecule responsible for trapping T cells in the lymph node? What reinforces this?

Answer 22

• CD69 (C-type lectin receptor) on the cell surface that degrades S1P1. By preventing “recovery” of this receptor on the lymphocyte, it is stuck in lymph node.)
• TCR stimulation

Question 23

What receptors regulate movement of activated lymphocytes into tissues?

Answer 23

integrins and chemokine receptors (on the lymphocytes)

Question 24

How common is Leukocyte Adhesion Deficiency? What causes it? What are symptoms? How is it treated?

Answer 24

• 1 in 100,000
• Defect in CD18, the Beta2 integrin subunit. Result is lack of LFA-1 expression. (unable to halt)
• Recurrent bacterial infections in childhood, umbilical separation delayed. Get abscesses. WBC count shows high neutrophils bcuz they are stuck in blood.
• Bone marrow transplant

Question 25

What do selections bind?

Answer 25

O-linked carbohydrate chains which are most commonly mucins.

Question 26

Chemokine receptors and integrins are always located(expressed) where ?

Answer 26

On the immune cell

Question 27

What is the purpose of L -selectin? What do they bind?

Answer 27

It is located on the t-cell and begins the rolling process in HEV’s.
L selectin binds GlyCAM, PNad, and MadCAM