Apoptosis

Question 1

characteristics in PM during apoptosis

Answer 1

PS gets evenly distributed on both sides of membrane via scramblase
-recognized/ingested by phagocytic cells before apoptotic bodies have chance to spill its dangerous contents

Question 2

characteristics in cytoplasm during apoptosis

Answer 2

cell shrinks (by ~1/3, and can tear
---> cause cytoskeletal change

Question 3

characteristics in nucleus during apoptosis

Answer 3

Nuclear collapse

• DNA condense (crescent) around nuclear envelope
• endonuclease cuts DNA in linkers between nucleosomes
  
  • –> extensive DNA damage via numerous simultaneous ds breaks

Question 4

zeiosis

Answer 4

boiling action of PM after shrinkage resulting in self tearing into apoptotic bodies
(get taken up by macrophages before it spills its dangerous contents)

Question 5

Why don’t macrophages recognize cells as apoptotic?

Answer 5

removal of apoptotic cells is physiological and silent

–> necessary for events that occur constantly throughout normal human body!

Question 6

morphology of necrosis

Answer 6

high amplitude swelling

-can no longer maintain ionic gradient

Question 7

common triggers of necrosis

Answer 7

1. ischemia following occlusion of major artery
2. physical/chemical trauma
3. overwhelming infection

Question 8

Importance in physiological/pathological process of necrosis

Answer 8

1. Trigger —> mitochondria swells
2. At “high amplitude swelling” stage, cell can no longer maintain ionic gradients/oxidative phosphorylation
3. Cell runs out of energy
4. Pumps fail and water floods in = cell lysis
5. Lysis releases intracellular contents into extracellular space = intense inflammatory response

Question 9

Tissues which there is most apoptosis occuring. Why?

Answer 9

thymus cells (lymphocytes):
very dangerous if damaged or mutated
- most sensitive cells to radiation (tiny dose causes lymphocyte to die)
- “better dead than wrong”

Question 10

Tissues which there is least apoptosis occuring. Why?

Answer 10

fibroblasts: leisure to repair more severe damage (continuum of response to injury) - less risky

only if damage is too overwhelming = apoptosis

Question 11

Role of caspases and mitochondrion in apoptosis

Answer 11

caspases are activated by series of intrinsic or extrinsic events which induce apoptosis

Question 12

caspases 3

-what activates it?

Answer 12

an EXECUTIONER/EFFECTOR

activated by caspase 9 or 8

Question 13

caspases 8

• what activates it?
• what does it activate?
• what pathway is it a part of?

Answer 13

is activated by FADD, which activates caspase 3

in extrinsic pathway

Question 14

caspases 9

• what activates it?
• what does it activate?
• what pathway is it a part of?

Answer 14

Known as ACTIVATOR caspase

is activated by Apaf-1 and activates caspase 3

in intrinsic pathway

Question 15

Bcl-2 and Bcl-Xl

Answer 15

anti-apoptotic factors

anti and pro apoptotic factors control signaling for mitochondrial apoptosis

Question 16

Cytotoxic/killer T cells (CTL)

Answer 16

responsible for surveillance and instructing target cells to undergo apoptosis thru extrinsic pathway

Question 17

Intrinsic pathway vs Extrinsic pathway of cell death

Answer 17

Intrinsic: involves anti and pro apoptotic factors which regulates caspase 9 and 3.

Extrinsic: involves CTL and upregulated expression of Fas/CD97, which activates caspase 3

but downstream pathways are the same.

Question 18

Novel way of looking at malignancy

Answer 18

if proliferation exceeds cell death:

• cells are dividing too fast
• cells not dying fast enough

Question 19

Difference between phagocytosis of apoptotic and necrotic cells

Answer 19

apoptotic cells: recognized/ingested by phagocytic cells before apoptotic bodies have chance to spill its dangerous contents
(not imflammatory)

necrotic cells:
intense inflammatory event = attract macrophages

Question 20

autoimmune lymphoproliferative syndrome (ALPS)

Answer 20

pathogenesis is failure of cells to die rather than uncontrolled proliferation

have mutation in Fas or FasL

Question 21

Kaposi’s sarcoma virus

Answer 21

Herpes virus HHV-8 have viral FLIPs that inhibits apoptosis signals

Question 22

FLippase

Answer 22

If PS accidentally gets flipped to outer leaflet of membrane, flippase immediately flips it back inside.

Question 23

Where do the intrinsic and extrinsic pathways take place?

Answer 23

intrinsic: mitochondrial
extrinsic: transmembrane