8. Apoptosis

Question 1

When might hyperproliferation occur?

Answer 1

Embryonic development - eg cell death to form digits

Question 2

When might cells become unnecessary and therefore require apoptosis?

Answer 2

Removal of mammary epithelium after lactation

Question 3

What is the main difference between necrosis and apoptosis?

Answer 3

Necrosis: Unregulated, associated with inflammation, cell may burst
Apoptosis: Proactive, not associated with inflammation, cell shrinks

Question 4

Summarise the mechanism of necrosis

Answer 4

Cytoplasmic proteases are released due to increased plasma membrane permeability –> autodigestion

Question 5

What are the 2 phases of apoptosis?

Answer 5

Latent and Execution

Question 6

Describe the latent phase of

apoptosis

Answer 6

Death pathways have been activated but there is no morphological change yet

Question 7

Recall the visible steps of the execution of apoptosis in the intestine

Answer 7

1. Loss of microvilli and cell-cell junctions
2. Cell shrinks
3. Asymmetry of plasma membrane lost due to “flipping” of lipids in membane (PTS appears on outer membrane)
4. Chromatin and nuclear condensation
5. DNA fragmentation
6. Formation of blebs, which are “thrown off” cell
7. Fragmentation into membrane-enclosed apoptotic bodies
   PLASMA MEMBRANE STAYS INTACT

Question 8

What is the fate of the apoptotic membrane?

Answer 8

Phagocytosis by macrophages - they emit chemotacticsignals as they die

Question 9

What is reponsable for executing cell death?

Answer 9

Caspases

Question 10

What is responsable for initiating the death programme?

Answer 10

Mitochondria and death receptors

Question 11

What does “caspases” stand for?

Answer 11

Cysteine-dependent aspartate-directed proteases

Question 12

How are caspases activated?

Answer 12

Proteases

Question 13

What 2 groups can the caspases be divided into? Recall their specific motifs

Answer 13

Initiators (CARD and DED subcategories)

Effectors

Question 14

What do CARD and DED stand for?

Answer 14

CARD = caspase recruitment domain
DED = death effector domain

Question 15

Recall which caspases are initiators and which are effectors

Answer 15

Initiators: 2, 9 = CARD; 8,10 = DED

Effectors = 1,2,3,6,7

Question 16

Summarise the maturation of caspases

Answer 16

1. Cleave inactive procaspase

2. Fold 2 large and 2 small chains = active heterotetramer

Question 17

Recall 2 functions of effector caspases

Answer 17

Cleave protein complexes to inactivate

Enzyme activation

Question 18

What are the 2 mechanisms of caspase cascade activation

Answer 18

Death by design or default

Question 19

Describe the structure of death receptors

Answer 19

Have a cytoplasmic membrane with a DD (death domain)

Question 20

What is needed to activate death receptors?

Answer 20

Death ligand eg. Fas or TNF-alpha

Question 21

Recall the key adaptors for triggering apoptosis and the function and structure of each

Answer 21

FADD: activate apoptosis (DED + DD)
FLIP: inhibit pathway (DED x 2)

Question 22

Recall the key adaptors for triggering apoptosis and the function and structure of each

Answer 22

FADD: activate apoptosis (DED + DD)
FLIP: inhibit pathway (DED x 2)

Question 23

What is Fas?

Answer 23

Death receptor that is upregulated when apoptosis is triggered

Question 24

Where does fas-fas-L binding occur?

Answer 24

Surface of cytotoxic t cells

Question 25

Recall how Fas/Fas-L leads to apoptosis

Answer 25

1. Binds on T cell –> trimerisaton
2. 3 cytoplasmic DD domains recruit FADD
3. FADD recruits PROcaspase 8 which interacts with its DED
4. Procaspase is cleaved to activate
5. Caspase 8 cleaves effector caspases to initiate death programme