13 Cellular Immunity 1 Flashcards
What are the 4 amino acid patterns of chemokines?
- CC
- CXC
- CX3C
- C or XC (lack 1st conserved cysteine)
T/F chemokines produce an intracellular signal?
False. (ish) Only the heterotrimeric G protein they are bound to produces the signal.
How many chemokine receptors are there? All of these have how many transmembrane domains in their accompanying G-protein?
- 18
- 7
What is the nomenclature for naming chemokines and receptors?
- CCL1- ligand
- CCR1- Receptor
Which cells can extravasate into lymph nodes through HEV’s? (high endothelial venules)
lymphocytes only (the rest all use lymphatics to get there)
Which important surfaces are the following molecules located on?
-L-selectin, P-selectin, E-selectin, CCL21, CXL12, LFA1, integrins
Endothelial cells: E and P selectin
Platelets: P selectin
Lymphocytes: L selectin, CCL21, CXL12, LFA-1 (an integrin)
Which selectins are constitutive and which are induced by inflammation?
- L is constitutueve
- E and P are inducible on blood vessel endothelium (and are constitutive in other body areas)
What are the “Other” surfaces where the 3 selectins are expressed? (may be unimportant?)
- L: myeloid cells (constitutive)
- E: skin endothelium (constitutive)
- P: choroid plexus, lung endothelium (constitutive)
What do selectins bind to?
carbohydrate structures. (which are usually on membrane-bound mucin proteins)
What molecule links a carb to a protein?
O linked carbohydrates (ser and thr)
What are integrins made up of?
alpha and beta chain (24 combinations of 8 dif beta and 18 dif alpha chains)
What activates an integrin? What does that accomplish? What is
- stimulation of TCR or chemokine receptor
- makes it extra sticky
LFA-1 integrin binds to what?
ICAM-1
Describe the process of interactions that results in leukocyte rolling and stopping?
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
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?
- 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.
What keeps S1P low in lymphoid and peripheral tissues?
S1P lyase
What directs Dendritic Cells to peripheral tissues?
Chemokine receptors
What directs Dendritic Cells to lymph nodes?
-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!)
Approximate amount of antigen-specific naive CD 8 and CD 4 cells?
- CD 8: 80-1,200
- CD4: 15-200
What is priming?
-activation of naive T cells following encounter w/ Ag
IL-2 binds what receptor? Which chain of that receptor is expressed first following priming? What function does IL-2 binding have?
- CD25
- alpha chain
- Drives clonal expansion, esp. of Th1 cells
What is the main molecule responsible for trapping T cells in the lymph node? What reinforces this?
- 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
What receptors regulate movement of activated lymphocytes into tissues?
integrins and chemokine receptors (on the lymphocytes)
How common is Leukocyte Adhesion Deficiency? What causes it? What are symptoms? How is it treated?
- 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
What do selections bind?
O-linked carbohydrate chains which are most commonly mucins.
Chemokine receptors and integrins are always located(expressed) where ?
On the immune cell
What is the purpose of L -selectin? What do they bind?
It is located on the t-cell and begins the rolling process in HEV’s.
L selectin binds GlyCAM, PNad, and MadCAM
