Cell Mediated Cytotoxicity Flashcards

1
Q

Humoral immunity

A

mediated by antibody and is responsible for protecting the extra-cellular environment from pathogens and toxins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Cell mediated immunity

A

recognizes pathogen-infected cells or cells that have undergone genetics alterations (tumor cells) and kills them
essential defense against intracellular pathogens, including viruses, some bacteria and some parasites.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Mediators of cell-mediated immunity

A
Antigen non-specific effector cells:
Natural killer (NK) cells
Macrophages
Neutrophils
Eosinophils

Antigen specific effector cells:
CD8+ T cells (cytotoxic T cells, CTLs, Tc cells)
CD4+ T cells (helper T cells, Th cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

CTL-P activated by

A

licensed APC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

APCs can be licensed by

A

Th1 or Th17 CD4+ cells (via CD40/CD40L) as well as by engagement of PAMPs with TLRs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Requirement for CD4+ T cell help for license APC? Generate CD8+ memory?

A

No for license APC

Yes for generate memory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Activation to effector CD8+ cell

A

Antigen-specific signal, transmitted by the TCR upon recognition of the proper peptide: MHC Class I complex presented by a licensed APC.

Co-stimulatory signal is transmitted by CD28:CD80/CD86 interaction between the CTL-P cell and the licensed APC.

IL-2 secreted by a Th1 or Th17 CD4+ T cell or the CTL itself results in the proliferation and differentiation of the antigen-activated CTL-P cell to a fully active CTL.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Naive CTL-P

A

Does not express IL-2 or the high affinity IL-2R (CD25) until after activation (no proliferation).
Expresses high levels of L-selectin and CCR7 (homing and retention in the lymph node).
Expresses low levels of CD44 and LFA-1.
No cytotoxic activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Effector CTL

A

Expresses high affinity IL-2R (CD25) and synthesizes IL-2.
Expresses low levels of L-selectin and CCR7.
Expresses high levels of CD44 and LFA-1 (homing and retention at sites of inflammation)
Exhibits cytotoxicity (starts to produce perforin and granzyme).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Memory CTL Cells

A

cells may not require Th1 CD4+ T cell help to reactivate.

Requires only low levels of IL-2 (can be produced by activated CTLs) for memory CTLs to become mature effector CTLs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

CCR7 and L-selectin

A

homing and retention in the lymph node

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

CD44 and LFA-1

A

homing and retention at sites of inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

CTL binding of the target cell

A

TCR-CD3 complex of CTL recognizes MHC/peptide
LFA-1 on CTL binds ICAMS
Antigen activation: LFA-1 –> high affinity then back to low affinity in 10 minutes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

CTL killing mechanisms

A

Perforin granzyme secretions
Fas ligand
TNFa production and secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Perforin and granzyme

A

Perforin molecules form a pore on target cell membranes.

Granzyme molecules activate apoptosis by cleavage of caspases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Fas ligand protein

A

Membrane-bound FasL binds to Fas on the membrane of the target cells and initiates killing
Activates apoptosis by cleavage of caspases

17
Q

Caspase cascade

A

Get 8, 2, 1 cleaved - all go to 3, 6, 7
8 also goes to Bid –> tBid at mitochondria –> cytochrome C –> caspase 9 –> 3,6,7

3, 6, 7 at high levels trigger apoptosis

18
Q

NK cells play major roles in killing

A

virus-infected cells, intracellular pathogen-infected cells and tumor cells

19
Q

Some NK cells can produce

A

IFN-gamma
IFN-γ tilts the immune response toward Th1 cells by inhibiting Th2 cells and inducing IL-12 production by macrophages and dendritic cells.
IFN-γ can activate macrophages (M1 – angry) and NK cells.

20
Q

NK cell activity is stimulated by

A

IFN-α, IFN-β, IFN-γ, TNF-α, and IL-15, IL-12

TYPE 1 INTERFERONS AND IL-12

21
Q

timing of NK cells

A

early - make IFNa and IFNb –> NK cells

before CTLs

22
Q

Nk cells express

A

CD16 (FcγRIIIA) and NKRs.

23
Q

NK cells do/do not undergo receptor gene rearrangement

A

DO NOT (no TCR or CD3)

24
Q

NK kill is/is not MHC restricted

A

IS NOT (no CD4 or CD8)

25
Q

NK cell killing mechansims

A

same as CTL
FasL expressed on the surface can kill cells expressing Fas
Perforin and granzyme released from granules
TNF expressed on the surface and secreted

26
Q

NK cells have both __ and __ receptors

A

Activation and inhibition

27
Q

2 categories of NK cell receptors

A

lectin-like (NKG2 family)

Immunoglobulin-like receptors (KIR)

28
Q

Lectin-like receptors

A
Binds to HLA-E and MHC class I-like molecules (NKG2D)
Most receptors are activating.
29
Q

KIRs

A
Bind to most MHC class I molecules  (HLA-A, HLA-B, and HLA-C)
Most receptors are inhibitory.
30
Q

CD25

A

IL-2R (high affinity)