Apoptosis

Question 1

What is necrosis?

Answer 1

• usually in tissues where injury was extreme or sudden
• mitochondria swells to “high amplitude swelling” and ATP production stops
• starved of ATP, plasma membrane’s ion pumps fail, cell swells and bursts
• intensely proinflammatory
• requires debris removal, injury resolution and, if the storm has been damaged, scar formation

Question 2

When does apoptosis occur?

Answer 2

cell death that is normal and predictable from relatively minor injury

Question 3

What are the defining features of apoptosis?

Answer 3

• early in process, produces signals on the cell that it is undergoing apoptosis -> membrane is intact when macrophage eats it
• no release of proinflammatory release of debris
• collapse of the nucleus; chromatin becomes supercondensed into, eventually, spherical beads
• DNA fragmented into smaller units by endonuclease on the DNA linkers

Question 4

What happens to the cell volume within the first few seconds of apoptosis?

Answer 4

it shrinks, losing about a third of its volume

Question 5

What is one of the markers for apoptosis?

Answer 5

phospholipid phosphatidylserine, usually on the inner leaflet of the lipid bilayer

Question 6

What allows for phospholipid phosphatidylserine to be on the exterior of an apoptotic cell?

Answer 6

Scramblase, distribution of PS is equal on both sides

Question 7

What enzyme prevents phospholipid phosphatidylserine from being on the exterior in a healthy cell?

Answer 7

flippase

Question 8

What are apoptotic bodies?

Answer 8

after the cell loses 1/3 of it’s volume, tears itself into apoptotic bodies some of which contain chromatin

Question 9

Does macrophages that recognize a cell as apoptotic become activated?

Answer 9

no, it’s anti-inflammatory

Question 10

Does low-dose radiation kill lymphocytes?

Answer 10

no, it induces them to kill themselves and must express “death genes”
- theoretically, all cells have “death genes”

Question 11

Why is morphogenetic death matter?

Answer 11

• determines the final shape of body parts and organs
• death by apoptosis between the digits give the final form to fingers and toes
• neuro - cells that survive are the ones that made the best connection

Question 12

How many times per second does mitosis occur in an adult human?

Answer 12

25 million times a second (so 25 million cells die)

Question 13

What happens when apoptosis doesn’t occur in a steady state system?

Answer 13

a tumor - cancer progression can be caused by mutations that inhibit cell death (ex. p53 inactive)

Question 14

What happens to the mitochondria in the beginning of apoptosis?

Answer 14

• anti-apoptotic members of Bcl-2 protein family (Bcl-2 and Bcl-Xl) are replaced by pro-apoptotic signals Bim and PUMA
• Triggers Bax to make the membrane permeable so it releases cytochrome C into the cytoplasm
• activates Apaf-1 (cytoplasmic protein)
• activates protease caspase-9
• activates protease caspase-3

Question 15

Caspase-9 is a ________ caspase, caspase-3 is an __________

Answer 15

Caspase-9 is a signal caspase, caspase-3 is an executioner

Question 16

What instructs mutated or infected cells to undergo apoptosis?

Answer 16

cytotoxic T cells

Question 17

Autoimmune lymphoproliferative syndrome (ALPS)

Answer 17

• lymphocytes cannot receive signal for apoptosis, so they don’t die
• accumulates lymphocytes to create bulk of tissue looks like lymphoma or Hodgkin
• mutations in either Fas or FasL

Question 18

What is the mechanism where cytotoxic T cells (CTL) triggers apoptosis?

Answer 18

• CTL upregulates Fas ligand (FasL)
• FasL engages Fas or CD95 on cell surface
• CD95 recruits FADD to activate caspase-8
• caspase-8 activates caspase-3 (same downstream effect)

Question 19

What does FLIP do?

Answer 19

• competes with caspase-8 to bind with FADD
• inhibits apoptosis signalling
• viruses can gain v-FLIPs to keep the cell alive until they finish their cell cycle

Question 20

What is the most sensitive cell type to radiation?

Answer 20

lymphocytes - commits suicide, does not try to repair