cell mediated cytotoxicity Flashcards
How do CTL precursors get activated?
by interacting with a “licensed” APC
What cell surface marker serves as a high affinity IL-2 receptor?
CD25+
When does a naive CTL-P start to express IL-2 or IL-2R (CD25)?
after activation
What does a naive CTL-P express to help keep it in the lymph node?
L-selectin
CCR7
also:
CD44 and LFA-1 (low levels)
What does the effector CTL express?
High affinity IL-2R (CD25)
LOW levels of L-selectin and CCR7
HIGH levels of CD44 and LFA-1 (to home in on inflammation)
starts to produce perforin and granzyme—>capable of cytotoxic killing
What do memory T-cells require for reactivation:
IL-2
**not necessarily Th1’s
Three main systems for cytotoxic killing:
perforin and granzyme
FAS-FASL —> apoptosis
TNF production
Whats the difference between CD56low and CD56high?
two types of NK cells
low have granules and are most effective killers of target cells (90% of nk’s in blood)
high release cytokines but have no granules (10% of nk’s in blood)
Which cytokines stimulate NK activity?
IFN-a, IFN-B, IFN-y, TNF-a, IL-15
What is CD16 on NK cells?
recognizes IgG
Two types of NK receptors?
Lectin like (NKG2)
- mostly activating EXCEPT NKG2A (inhibitory)
- NKG2D—D=DEATH
KIR (killer cell immunoglobulin-like receptor)
-mostly inhibitory
What do NKG2’s bind to?
HLA-E and MHC I-like molecules
What do KIR’s bind to?
HLA-A,B,C
How do NK cells get activated?
bump into an inhibitory signal (ie. NKG2A) at least once (to prove it can be inhibited and won’t go rogue)
**this prevents autoimmunity
Review slide 29 for….
Antibody-Dependent Cell mediated Cytotoxicity
ADCC
Effector molecules of CD8+?
IL-2R (a lot)
L-selectin/CCR7 (a little)
CD44/LFA-1 (a lot)
Perforin/Granzymes
Effector molecules of NK’s?
INF-y (increases Th1’s, decreases Th2’s)
-makes angry Mac’s
Induces IL-12 from Mac’s/Dend’s
Which cells give APC’s their “license”?
Th1
Th17
Compare CD8s and NKs:
Antigen response:
Memory:
MHC restriction:
Thymus education:
CD8s NKs
TCR/CD3–MHC I cells lacking MHC I
LFA-1—-ICAM
FASL—FAS
secrete TNF
yes ?
MHC I none
yes no
Only NKG2 (lectin like) that is inhibitory?
What is its ligand?
NKG2A
HLA-E
Only NKG2 that doesn’t bind HLA-E?
What does it bind?
NKG2D
ULBPs, MIC A/B
Only KIR that is activating?
What does it bind?
KIR2DS1
HLA-C2
Antibody dependent cell mediated cytotoxicity:
What cells involved? How do they bind?
NK's Macs Monos Neuts Eos
bind Ig via Fc receptor
Which cells participate in ADCC with enzyme release killing?
Macs
Eos
Neuts
