Diebel- Cell mediated cytotoxicity Flashcards Preview

IHO Week 4 > Diebel- Cell mediated cytotoxicity > Flashcards

Flashcards in Diebel- Cell mediated cytotoxicity Deck (48):
1

What does cell mediated immunity do?

Recognizes pathogen infected cells/cells w/ genetic alterations and kills them

2

What are antigen non-specific effector cells?

NK cells:
Macrophages
Neutrophils
Eosinophils

3

What are antigen specific effector cells?

CD8 T cells
CD4 T cells

4

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

5

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

6

What is a CTL-P? When does it mature?

Naive T cell

Matures after interaction w/ Th CD4 T cell

7

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

8

What are the two ways to license a DC?

1. Engagement w/ activated CD40L and Helper T
2. Indirect interaction w/ pathogen--TLR molecule

9

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

10

Which type of DC licensing (CD4 or TLR) is better for optimal proliferation/memory generation?

CD4 T cell

11

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

12

What type of IL-2R does a mature CTL express?

HIGH affinity IL-2 R that requires high levels of IL-2 to proliferate

13

What are other characteristics of CTLs in regards to IL-2, adhesion molecules, cytotoxicity, etc.?

Synthesizes LOW levels of IL-2
Expresses CD45RO
HIGH levels of CD2 and LFA-21
Exhibits cytotoxicity

14

What IL is required to reactivate a memory CTL?

LOW levels of IL-2 for memory cells to become mature effector cells

15

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

16

What are the molecules used for CTL killing?

perforin, granzyme, fas, TNF

17

MOA: perforin

Forms pore >
granzyme molecules go through

18

MOA: granzyme

pass through pore formed by perforin>
activate apoptosis by cleavage of caspaces

19

MOA: Fas L

Membrane bound Fas L binds to Fas on membrane of target cell and initiates killing
Activates apoptosis by cleavage of caspaces

20

MOA:TNF

CTLS kill by TNF production and secretion

21

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

22

What do NK cells do?

Kill virus infected cells
intracellular pathogen infected cells
tumor cells

EARLY defense against virus

23

NK cells are induced by....

IFN, alpha, beta, gamma
TNF alpha
IL 15

24

NK cells produce...

IFN-y

25

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

26

What are the differences between NK and CTL?

NK:
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

27

What is similar between NK and CTLs?

KILLING

NK uses FasL, perforin, granzyme and TNF just like the other big kids

28

What are the two types of receptors found on NK cells?

Lectin like
KIR

29

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

30

The inhibitory lectin receptor has what components?

NKG2A w/ intracellular ITIMS

31

The non-inhibitory lectin receptor has what components?

NKG2C w/ charged lysine residue that allows it to interact w/ ITAM

I think ITAM.

32

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

33

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

34

What happens if an antigen recognition signal is given to NK cells and MHC I levels are HIGH?

NO KILLING

35

What happens if an antigen recognition signal is given to NK cells and MHC I levels are LOW?

Killing

36

What does HLA-E do?

Presents leader peptides from MHC I molecucles and presents them to NK CD94 cells

37

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

38

If both activating and inhibitory signals are stimulating NK cells what happens?

Inhibitory overrides the activating

39

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

40

NK cells express _____ and _____ receptors.

CTL express _____ and _______ receptors.

lectin like, KIR

TCR, CD3

41

How are NKT cells different from CTLS?

TCR is invariant
TCR doesn't recognize MHC bound peptides but does recognize glycolipids presented by CD1d
NO memory

42

What surface markers do NKT cells represent

CD4+/-

43

What do NKT cells do?

kill bacteria and tumor cells

44

What effector cells are associated w/ ADCC?

NK
macrophages
monocytes
neutrophils
eosinophils

45

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)

46

What cells release TNF?

NK
monocytes
macrophages

47

What cells release peforin?

NK
eosinophils

48

What cells release granzye?

NK