Flashcards in Diebel- Cell mediated cytotoxicity Deck (48):
What does cell mediated immunity do?
Recognizes pathogen infected cells/cells w/ genetic alterations and kills them
What are antigen non-specific effector cells?
What are antigen specific effector cells?
CD8 T cells
CD4 T cells
What are three ways to induce the cytotoxic response?
1. Non-self recognition: CTL recognizes MCHI bound to non-self antigen
2. Missing self recognition: NK binds to cell w/ activated ligand but lacks MCH I
3. Recognition of stress induced ligands: NK receptor binds activating ligand and stress induced ligand
What are the two mechanisms CTLs and NK cells use to kill? How is this different from NK T cells?
Cytotoxic granules and FASL-FAS interactions
NK T cells use FASL interactions predominately but can also activate NK cells INDIRECTLY
What is a CTL-P? When does it mature?
Naive T cell
Matures after interaction w/ Th CD4 T cell
What are the three sequential signals necessary for CTL-P maturation?
1. antigen specific signal- TCR recognizing MCH II
2. costimulatory signal- CD28:B7
3. Th1--> secretes IL-2--> proliferation and differentiation of CTL-P to CTL
What are the two ways to license a DC?
1. Engagement w/ activated CD40L and Helper T
2. Indirect interaction w/ pathogen--TLR molecule
What control mechanism is used to prevent self recognition by CTLs?
An antigen is only presented to CTL-P through MCH I AFTER:
1. APC has "found" an pathogen through a TLR
2. A CD4 has "told" it that it has found a pathogen
Which type of DC licensing (CD4 or TLR) is better for optimal proliferation/memory generation?
CD4 T cell
What does a naive CTL-P express and what does it NOT?
CD45RA--(differentiates naive from mature)
Low levels of CD2 and LFA-1
NO IL-2 or IL-2R
NO cytotoxic activity
What type of IL-2R does a mature CTL express?
HIGH affinity IL-2 R that requires high levels of IL-2 to proliferate
What are other characteristics of CTLs in regards to IL-2, adhesion molecules, cytotoxicity, etc.?
Synthesizes LOW levels of IL-2
HIGH levels of CD2 and LFA-21
What IL is required to reactivate a memory CTL?
LOW levels of IL-2 for memory cells to become mature effector cells
How do mature CTLs bind target cells?
1. TCR recognizes MCH I on target cell
2. LFA I on CTL binds ICAM on target cell
3. Antigen activation converts LFA 1 from low to high affinity state for better binding
4. After 5-10 mins LFA-1 returns to low affinity state--> dissociation of CTL from target cell
What are the molecules used for CTL killing?
perforin, granzyme, fas, TNF
Forms pore >
granzyme molecules go through
pass through pore formed by perforin>
activate apoptosis by cleavage of caspaces
MOA: Fas L
Membrane bound Fas L binds to Fas on membrane of target cell and initiates killing
Activates apoptosis by cleavage of caspaces
CTLS kill by TNF production and secretion
What are the two main pathways to apoptosis?
1. Serine proteases (granzymes) cleave Bid and procaspace 3--> apoptosis
2. FasL binds Fas and activates death domains that cleave caspace 8--> apoptosis
What do NK cells do?
Kill virus infected cells
intracellular pathogen infected cells
EARLY defense against virus
NK cells are induced by....
IFN, alpha, beta, gamma
NK cells produce...
What does IFN-y do?
1. tilts IR toward Th1 cells (inhibit Th2 and induce IL-12 production by macrophages and DC)
2. Activates M1 and NK
What are the differences between NK and CTL?
express CD 16 and FcyRIII
Not educated in the thymus (not antigen driven)
Don't undergo rearrangement of receptor genes
Killing is NOT restricte to MCH
What is similar between NK and CTLs?
NK uses FasL, perforin, granzyme and TNF just like the other big kids
What are the two types of receptors found on NK cells?
What binds to lectin-like receptors? and what components make up the lectin receptor?
proteins rather than polysaccharides
CD94 associates w/ membors of the NKG2 family via a disulphide bond
The inhibitory lectin receptor has what components?
NKG2A w/ intracellular ITIMS
The non-inhibitory lectin receptor has what components?
NKG2C w/ charged lysine residue that allows it to interact w/ ITAM
I think ITAM.
What are KIR receptors? What do they bind to? When do they appear?
Immnoglobulin like receptors
bind to MHC class I
Late in maturation when the cell is ready to perform effector function
What is the difference between the inhibitory KIR and the activating KIR?
Inhibitory- long cytoplasmic tials that contain ITIM
Activating- short cytopalsmic tails w/ a charged lysine residue which allows them to associate w/ ITAM
What happens if an antigen recognition signal is given to NK cells and MHC I levels are HIGH?
What happens if an antigen recognition signal is given to NK cells and MHC I levels are LOW?
What does HLA-E do?
Presents leader peptides from MHC I molecucles and presents them to NK CD94 cells
What is the advantage of having HLA-E?
It's a fall back mechanism to prevent NK cell killing when you have trouble getting MHC I out to surface or when there isn't proper loading.
HLA-E prevents NK killing
If both activating and inhibitory signals are stimulating NK cells what happens?
Inhibitory overrides the activating
How do NK cells and CTL cells complement each other?
NK MAKS presence of foreign antigen on MHC I
CTL EXPRESS foreign antigen on MCH I
NK cells express _____ and _____ receptors.
CTL express _____ and _______ receptors.
lectin like, KIR
How are NKT cells different from CTLS?
TCR is invariant
TCR doesn't recognize MHC bound peptides but does recognize glycolipids presented by CD1d
What surface markers do NKT cells represent
What do NKT cells do?
kill bacteria and tumor cells
What effector cells are associated w/ ADCC?
What is the mechanism by which ADCC cells kill?
Bind antigen via ab through Fc receptor
Killing is mediated by cytosolic enzyme release (TNF, perforin, granzyme depending on the cell)
What cells release TNF?
What cells release peforin?