Cell Mediated Cytotoxicity

Question 1

Humoral immunity

Answer 1

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

Question 2

Cell mediated immunity

Answer 2

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.

Question 3

Mediators of cell-mediated immunity

Answer 3

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)

Question 4

CTL-P activated by

Answer 4

licensed APC

Question 5

APCs can be licensed by

Answer 5

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

Question 6

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

Answer 6

No for license APC

Yes for generate memory

Question 7

Activation to effector CD8+ cell

Answer 7

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.

Question 8

Naive CTL-P

Answer 8

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

Question 9

Effector CTL

Answer 9

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).

Question 10

Memory CTL Cells

Answer 10

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

Question 11

CCR7 and L-selectin

Answer 11

homing and retention in the lymph node

Question 12

CD44 and LFA-1

Answer 12

homing and retention at sites of inflammation

Question 13

CTL binding of the target cell

Answer 13

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

Question 14

CTL killing mechanisms

Answer 14

Perforin granzyme secretions
Fas ligand
TNFa production and secretion

Question 15

Perforin and granzyme

Answer 15

Perforin molecules form a pore on target cell membranes.

Granzyme molecules activate apoptosis by cleavage of caspases.

Question 16

Fas ligand protein

Answer 16

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

Question 17

Caspase cascade

Answer 17

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

Question 18

NK cells play major roles in killing

Answer 18

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

Question 19

Some NK cells can produce

Answer 19

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.

Question 20

NK cell activity is stimulated by

Answer 20

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

TYPE 1 INTERFERONS AND IL-12

Question 21

timing of NK cells

Answer 21

early - make IFNa and IFNb –> NK cells

before CTLs

Question 22

Nk cells express

Answer 22

CD16 (FcγRIIIA) and NKRs.

Question 23

NK cells do/do not undergo receptor gene rearrangement

Answer 23

DO NOT (no TCR or CD3)

Question 24

NK kill is/is not MHC restricted

Answer 24

IS NOT (no CD4 or CD8)

Question 25

NK cell killing mechansims

Answer 25

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

Question 26

NK cells have both __ and __ receptors

Answer 26

Activation and inhibition

Question 27

2 categories of NK cell receptors

Answer 27

lectin-like (NKG2 family)

Immunoglobulin-like receptors (KIR)

Question 28

Lectin-like receptors

Answer 28

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

Question 29

KIRs

Answer 29

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

Question 30

CD25

Answer 30

IL-2R (high affinity)