Lecture 20

Question 1

Where are Fas and CD40 ligand expressed

Answer 1

Both expressed on surface of effector T cells (NOT on naive T cells)
Crucial for effector T cell function
Transmembrane ligands of TNF family

Question 2

Which cells express Fas ligand

Answer 2

Fas ligand is expressed on surface of effector CD8+ cells and TH1 cells

Question 3

What does Fas ligand bind to

Answer 3

Binds to Fas on surface of infected cells in periphery

Question 4

What cells express CD40 ligand

Answer 4

CD40 ligand is expressed on surface of TH1, TH2, TH17, and TFH cells

Question 5

What does CD40 ligand bind to

Answer 5

CD40 ligand binds to CD40 on B cells and innate immune cells

Question 6

Action of CD40 ligand binding

Answer 6

Activate target cells
Allows for dendritic cell licensing and expression of more co-stimulatory molecules

Question 7

Action of Fas ligand binding

Answer 7

Exert cytotoxic effect when expressed on surface of CD8+ T cells

Question 8

Naive CD8+ T cell precursors generate

Answer 8

Effector Cytotoxic T lymphocytes (CTL)

Question 9

Signal 1

Answer 9

TCR binds peptide presented by APC on MHC class 1

Question 10

Signal 2

Answer 10

Costimulatory signal transmitted by CD28-B7 (CD80/CD86) interaction between the T cell and APC

Question 11

Signal 3

Answer 11

Provided mainly by IL-2 and other cytokines to some extent (IL-12), inducing proliferation and differentiation into CTL form

Question 12

How do CTLs recognize and kill infected/tumor cells

Answer 12

Via recognition with their TCR

Question 13

Specialties of CD8+ T cells

Answer 13

Require help of effector CD4+ T cells
Require more costimulation
Cytokine release (IL-2) can be autocrine and paracrine from TH1 or TH17 cells

Question 14

Simple and Rarest way CD8+ T cell are activated

Answer 14

By dendritic cells with high co-stimulatory activity

Question 15

Most common way CD8+ T cells are activated

Answer 15

Help from CD4 effector T cells and licensed cross presenting dendritic cells

Question 16

Main consequence of CD40 signaling

Answer 16

CD40 signaling leads to dendritic cell licensing and expression of more co-stimulatory molecules

Question 17

CD8+ T cell activation requires

Answer 17

1) CD4+ T cell to find p:MHC class II match
2) CD4+ to receive all 3 signals
3) CD4+ to express CD40 ligand which binds to CD40 on APC

Question 18

Pathway for antigen presentation by dendritic cells to BOTH CD4+ and CD8+ T cells

Answer 18

Dendritic cell encounters PAMP–>travels to secondary lymphoid organ (lymph node)–>present antigen on MHC Class II to CD4+ T cell–>get licensed through CD40 binding–>present exogenous antigen on MHC class I to CD8+ T cell

Question 19

Consequences of CD4+ T cell activation

Answer 19

1) IL-2 secretion
2) CD40L expression

Question 20

Mechanism if Fas-FasL mediated CTL killing

Answer 20

Effector CTL expresses FasL, infected cells express Fas–>Fas and FasL bind–>signaling cascade–>cleavage of procaspase 3 and 7–>caspase (active) which releases apoptotic enzymes–>apoptosis of target cell

Question 20

CTL (cytotoxic T lymphocyte) effector functions

Answer 20

1) Induce apoptosis to kill infected cells (through Fas-FasL and Granules)
2) Secrete cytokines to direct immune response

Question 21

Mechanism of Granule-mediated killing

Answer 21

CTL interacts with target cell via nonspecific adhesion–>specific recognition is by TCR:pMHC–>triggers intracellular signaling–>reorganization of cytoskeleton–>Granules released at point of cell contact–>perforin and granzyme B are released from granules (proteins)–>perforin forms pores–>granzyme B are serine proteases–>granzyme B induces apoptosis directly through procaspases cleavage –>caspases, and perforin (indirectly)

Question 22

Main action of perforin

Answer 22

Pore-forming protein, makes holes in membrane to help deliver granule contents

Question 23

Main action of Granzyme B

Answer 23

Serine protease which activate apoptosis once in the target cell’s cytoplasm

Question 24

Classic sign of apoptosis

Answer 24

Membrane blebbing
When membrane bulges outward due to cytoskeleton break/nuclear collapse

Question 25

Where do Fas-FasL and Granule mediated killing converge

Answer 25

On Caspase 3 activation leading to apoptosis