Apoptosis Flashcards Preview

Molecules to Medicine III > Apoptosis > Flashcards

Flashcards in Apoptosis Deck (24)
1

Name 3 tissues where apoptosis is especially important

skin
gut
immune system (lymphocytes: T-cells 95-99% rejection rate)
Nerves (only correct connections at correct time kept/ best connections)
Development: between fingers and toes die

2

Name a pathology caused by failure of apoptosis

NEW***
autoimmune lymphoproliferative syndrome

3

Name a pathology caused by inappropriate apoptosis

Alzheimer's

4

Describe necrosis

1. Mitochondria fail - can no longer maintain ionic gradient needed for oxidative phosphorylation.
2. Cell runs out of ATP - membrane ion pumps fail, water floods into cell - swells
3. Cell bursts- small intracellular molecules are intensely pro inflammatory
4. Immune response - wbc, especially macrophages arrive and remove debris- resolve injury- form scar (if stroma damaged)

5

What causes necrosis?

ischemia
physical/ chemical trauma
infection

6

How is apoptosis different from necrosis?

normal and predictable: result of relatively minor injury
physiological death- not mechanical
expected and implies renewal (like leaves off trees in fall)

7

What is the defining feature of apoptosis?

collapse of the nucleus

8

What happens during nuclear collapse?

Chromatin-> super-condensed (crecents- spherical featureless beads)
Fragmentation of DNA by endonuclease (180bp lengths)

Cell can only repair a few simultaneous DSBs=> even if it survives nuclear collapse, THE CELL WILL NEVER DIVIDE AGAIN!

9

What are the cytoplasmic and plasma membrane events of apoptosis?

cell loses up to 1/3 of volume (pulls away from neighbors)
Boiling action of plasma membrane (ZEIOSIS) ->

Cell tears itself apart into apoptotic bodies

10

Why are apoptotic cells phagocytose d?

so they cannot spill their dangerous contents

11

Describe the phospholipid phosphatidylserine (PS) system of apoptosis

Phospholipid phosphatidylserine (PS) usually within inner leaflet of lipid bilayer

SCRAMBLASE: allows PS to become equal on each side of membrane

Phagocytic cells have receptors for PS- recognize-> bind-> ingest cells once they commit to apoptosis before they lyse

12

What is the function of flipase

returns PS to inner leaflet of lipid bilayer in healthy cells

13

What are the key differenced between phagocytosis of apoptitic cells and necrotic cells?

APOPTOSIS:
0 inflammatory response
normal
physiological & silent


NECROSIS:
opposite

14

How is apoptosis related to tumor formation/ progression?

Theory that mutation causes cell to continue growing -> when faced with lack of resources SECOND mutation prevents/ makes cell more resistant to apoptosis -> survives and continues

Estimated 7 mutations necessary to reach clinical malignancy

Mutations inhibiting death = stimulate growth in tumor cells

15

What initiates the intrinsic pathway of apoptosis?

Mitochondrial outer membrane function compromised (withdraw growth factor/ other signal)


16

What are the "anti-apoptotic" proteins?

Bcl-2
Bcl- XL
Ususally guard outer mitochondrial membrane

17

What are the "pro-apoptotic" proteins?

Bim
PUMA
replace Bcl-'s
allowing Bak and Bax to act on membrane

18

what effect do Bak and Bax have on the cell membrane?

Make it permeable -> cytochrome C released into cytoplasm

19

Describe the signaling cascade once cytochrome C enters cytoplasm

cytochrome C -> Apaf-1 activated -> protease caspase-9 activated -> caspase 3 activated => APOPTOSIS

20

What are the nicknames of caspase 9 and caspase 3?

caspase-9: signal caspase
caspase-3: executioner

21

How do cytotoxic killer T (CTL) cells induce extrinsic apoptosis?

CTL -> activate Fas/CD95 -> transduces signal across membrane -> recruits FADD-> activates caspase 8 -> activates caspase 3 -> APOPTOSIS

22

What is the root cause of autoimmune lymphoproliferative syndrome?

failure of cells to die (v. uncontrolled proliferation)

23

What is the importance of hte FLIP family of enzymes in viral infections?

FLIPs and v-FLIPS (viral) compete with caspase-8 to bind with FADD -> slowing apopotosis pathway and making cell a "zombie" that produces new viral copies

Herpes
Kaposi's sarcoma

24

Why are mutations to lymphocytes especially dangerous?

minor changes (binding of antigen to cell receptor) can drive lymphocyte into rapid cycle: 1 cell => 64,000 cells in 4 days!!
- if mutated- change locked in!
"better dead than wrong"