Apoptosis

Question 1

What is apoptosis?

Answer 1

Regulated, programmed form of cell death

Question 2

What is apoptosis used for?

Answer 2

• Eliminate damaged, infected or unneccesary cells
• Maintain tissue health with minimal inflammation

Question 3

How does necrosis compare to apoptosis?

Answer 3

Unregulated, causing cell swelling, rupture and inflammatory damage

Question 4

What are the 3 phases of apoptosis?

Answer 4

• Initiation
• Commitment
• Execution

Question 5

What is the initiation stage of apoptosis?

Answer 5

• Triggered by death receptors, cell damage or pathogen signals

Question 6

What is the commitment stage of apoptosis?

Answer 6

• Changes in gene expression/mitochondrial membrane permeability
• Release of caspases and hydrolases

Question 7

What is the execution stage of apoptosis?

Answer 7

DNA fragmentation, membrane blebbing and cell breakdown

Question 8

What are the two pathways of apoptosis?

Answer 8

Extrinsic and intrinsic pathway

Question 9

What is each apoptosis pathway mediated by?

Answer 9

Extrinsic pathway = death receptor-mediated
Intrinsic pathway = mitochondria-mediated

Question 10

What is the trigger for the extrinsic apoptosis pathway?

Answer 10

Triggered by external ligands like TNF, LPS, dsRNA

Question 11

What is the trigger for intrinsic apoptosis pathway?

Answer 11

Triggered by stress, DNA damage, toxins, or granzyme B

Question 12

What happens after external ligands are triggered in extrinsic pathway?

Answer 12

Activates caspase 8 and downstream executioner caspases

Question 13

What happens after the intrinsic pathway is triggered?

Answer 13

Mitochondria release cytochrome c, forming an apoptosome
This activates caspase-9, then executioner caspases

Question 14

What are caspases?

Answer 14

Cysteine proteases that cleave after aspartate residues

Question 15

What are the initiator caspases?

Answer 15

Caspase-8 (extrinsic) and 9 (intrinsic)

Question 16

What are the executioner capsases?

Answer 16

Caspases-3, 6, and 7

Question 17

What is the impact of caspases?

Answer 17

• DNA fragmentation
• Collapse of nuclear lamina
• Cytoskeleton disassembly
• Apoptotic body formation

Question 18

When does apoptosis occur (signal-wise)?

Answer 18

When pro-apoptotic signals are stronger than anti-apototic signals

Question 19

What are three inhibition mechanisms?

Answer 19

• Bcl-2 family proteins
• IAPs
• Transcriptional regulation

Question 20

How do Bcl-2 family proteins inhibit apoptosis?

Answer 20

Prevent cytochrome c release from mitochondria

Question 21

What are IAPs, and how do they inhibit apoptosis?

Answer 21

• Inhibitors of Apoptosis Proteins
• Directly inhibit caspases

Question 22

What is the main protein involved in transcriptional regulation of apoptosis?

Answer 22

p53- it activates pro-apoptotic genes (like Bax and Bak), and represses Bcl-2 proteins

Question 23

What cells can induce apoptosis as viral defence?

Answer 23

Cytotoxic T cells and natural killer cells

Question 24

What do cytotoxic T cells and NK cells release?

Answer 24

• Perforin: creates membrane pores
• Granzyme B: enters cell and activates caspases

Question 25

How do pathogens modulate apoptosis to their advantage?

Answer 25

- Inhibiting apoptosis of infected cells - Inducing apoptosis of immune cells

Question 26

What are two examples of viruses that can inhibit apoptosis?

Answer 26

- Epstein-Barr virus - Hepatitis B

Question 27

How does Epstein-Barr Virus inhibit apoptosis?

Answer 27

Encodes Bcl-2 homologues, which prevent cytochrome c release from mitochondria (activator of apoptosis)

Question 28

How does Hepatitis B inhibit apoptosis?

Answer 28

pX protein inhibits p53

Question 29

What is an example of a parasite that inhibits apoptosis, and how?

Answer 29

T. gondii activates NF-kB, which induces IAPs

Question 30

What is an example of a bacteria that inhibits apoptosis?

Answer 30

Mycobacterium tuberculosis inhibits apoptosis of infected macrophages. Does this through activating NF-κB, which upregulates host IAPs and Bcl-2 to block caspases and mitochondrial death signalling.

Question 31

What is an example of a bacteria that activates apoptosis, and how?

Answer 31

- Shigella - Releases IpaB, which activates caspase-1 - Causes macrophage apoptosis

Question 32

What are two examples that have mixed modulation of apoptosis?

Answer 32

- T. cruzi - Chlamydia trachomatis

Question 33

Why does T. cruzi inhibit apoptosis?

Answer 33

- Inhibits apoptosis in infected cells - Allows completion of intracellular life cycle - Upregulation of Bcl-2

Question 34

For what and how does T. cruzi induce apoptosis?

Answer 34

- Induces apoptosis of uninfected CD4 T cells - Does this via Fas/FasL signalling

Question 35

What is Fas/FasL signalling?

Answer 35

- Fas = death receptor - FasL = Fas ligand - When FasL binds Fas, it induces phagocytosis via activation of caspase-8

Question 36

When does Chlamydia trachomatis inhibit apoptosis?

Answer 36

During early infection- prevents apoptosis of infected epithelial cells to ensure intracellular replication

Question 37

How does C. trachomatis inhibit apoptosis?

Answer 37

Mechanism not entirely clear, but may include blocking of caspase activation

Question 38

When does chlamydia spp induce apoptosis?

Answer 38

Once replication is complete, leading to lysis and release of infectious particles

Question 39

How does chlamydia spp. induce apoptosis?

Answer 39

May involve upregulation of Bax (pro-apoptotic protein)