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IHO Week 4 > Diebel- Cell mediated cytotoxicity > Flashcards

Diebel- Cell mediated cytotoxicity Flashcards

1
Q

What does cell mediated immunity do?

A

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

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2
Q

What are antigen non-specific effector cells?

A

NK cells:
Macrophages
Neutrophils
Eosinophils

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3
Q

What are antigen specific effector cells?

A

CD8 T cells

CD4 T cells

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4
Q

What are three ways to induce the cytotoxic response?

A
  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
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5
Q

What are the two mechanisms CTLs and NK cells use to kill? How is this different from NK T cells?

A

Cytotoxic granules and FASL-FAS interactions

NK T cells use FASL interactions predominately but can also activate NK cells INDIRECTLY

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6
Q

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

A

Naive T cell

Matures after interaction w/ Th CD4 T cell

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7
Q

What are the three sequential signals necessary for CTL-P maturation?

A
  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
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8
Q

What are the two ways to license a DC?

A
  1. Engagement w/ activated CD40L and Helper T

2. Indirect interaction w/ pathogen–TLR molecule

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9
Q

What control mechanism is used to prevent self recognition by CTLs?

A

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
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10
Q

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

A

CD4 T cell

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11
Q

What does a naive CTL-P express and what does it NOT?

A

CD45RA–(differentiates naive from mature)
Low levels of CD2 and LFA-1

NO IL-2 or IL-2R
NO cytotoxic activity

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12
Q

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

A

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

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13
Q

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

A

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

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14
Q

What IL is required to reactivate a memory CTL?

A

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

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15
Q

How do mature CTLs bind target cells?

A
  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
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16
Q

What are the molecules used for CTL killing?

A

perforin, granzyme, fas, TNF

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17
Q

MOA: perforin

A

Forms pore >

granzyme molecules go through

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18
Q

MOA: granzyme

A

pass through pore formed by perforin>

activate apoptosis by cleavage of caspaces

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19
Q

MOA: Fas L

A

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

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20
Q

MOA:TNF

A

CTLS kill by TNF production and secretion

21
Q

What are the two main pathways to apoptosis?

A
  1. Serine proteases (granzymes) cleave Bid and procaspace 3–> apoptosis
  2. FasL binds Fas and activates death domains that cleave caspace 8–> apoptosis
22
Q

What do NK cells do?

A

Kill virus infected cells
intracellular pathogen infected cells
tumor cells

EARLY defense against virus

23
Q

NK cells are induced by….

A

IFN, alpha, beta, gamma
TNF alpha
IL 15

24
Q

NK cells produce…

25
Q

What does IFN-y do?

A
  1. tilts IR toward Th1 cells (inhibit Th2 and induce IL-12 production by macrophages and DC)
  2. Activates M1 and NK
26
Q

What are the differences between NK and CTL?

A

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
Q

What is similar between NK and CTLs?

A

KILLING

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

28
Q

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

A

Lectin like

KIR

29
Q

What binds to lectin-like receptors? and what components make up the lectin receptor?

A

proteins rather than polysaccharides

CD94 associates w/ membors of the NKG2 family via a disulphide bond

30
Q

The inhibitory lectin receptor has what components?

A

NKG2A w/ intracellular ITIMS

31
Q

The non-inhibitory lectin receptor has what components?

A

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

I think ITAM.

32
Q

What are KIR receptors? What do they bind to? When do they appear?

A

Immnoglobulin like receptors

bind to MHC class I

Late in maturation when the cell is ready to perform effector function

33
Q

What is the difference between the inhibitory KIR and the activating KIR?

A

Inhibitory- long cytoplasmic tials that contain ITIM

Activating- short cytopalsmic tails w/ a charged lysine residue which allows them to associate w/ ITAM

34
Q

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

A

NO KILLING

35
Q

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

36
Q

What does HLA-E do?

A

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

37
Q

What is the advantage of having HLA-E?

A

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
Q

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

A

Inhibitory overrides the activating

39
Q

How do NK cells and CTL cells complement each other?

A

NK MAKS presence of foreign antigen on MHC I

CTL EXPRESS foreign antigen on MCH I

40
Q

NK cells express _____ and _____ receptors.

CTL express _____ and _______ receptors.

A

lectin like, KIR

TCR, CD3

41
Q

How are NKT cells different from CTLS?

A

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

42
Q

What surface markers do NKT cells represent

43
Q

What do NKT cells do?

A

kill bacteria and tumor cells

44
Q

What effector cells are associated w/ ADCC?

A 
NK
macrophages
monocytes
neutrophils
eosinophils
45
Q

What is the mechanism by which ADCC cells kill?

A

Bind antigen via ab through Fc receptor

Killing is mediated by cytosolic enzyme release (TNF, perforin, granzyme depending on the cell)

46
Q

What cells release TNF?

A

NK
monocytes
macrophages

47
Q

What cells release peforin?

A

NK

eosinophils

48
Q

What cells release granzye?

IHO Week 4 (15 decks)

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