Apoptosis

Question 1

Where most frequent?

Answer 1

Skin, gut, immune system

Question 2

Necrosis

Answer 2

Not programmed. Cell bursts and releases contents, causes inflammation.

Question 3

Necrosis mechanism

Answer 3

Mito starts to swell. Then run out of ATP. PM pumps fail. H20 flows in. Cell swells and bursts.
Intracell contents are pro-inflamm. Attract white cells (macrophages)… effect of this is debris removal, injury resolution, or scar formation.

Question 4

Apoptosis

Answer 4

Minor injury or short lived cells.

More physiological than necrosis. “programmed” cell death.

Question 5

Apoptosis features

Answer 5

Collapse of nucleus. Super-condensation of chromatin (crescents/beads). Fragment DNA into single nucleosome units.
Endonuclease acts on linkers b/w nucleosome (attacks them), so many DSB’s cell dies or cannot replicate.

Question 6

Apoptosis changes

Answer 6

Cell shrinks rapidly and PM boils (zeiosis) in response, cell tears into apoptotic bodies, macrophage eats these.
Necessary to prevent content spillage!
Membrane still intact when eaten! although permeable.

Question 7

PS

Answer 7

eat me signal. Phagocytes recognize. Annexin binds PS.

Question 8

Apoptosis and changes in PM

Answer 8

PS should be on inside (flippase ensures it is), with apoptosis scramblase flips PS (equally distributed on both sides now).
Phagocytes see PS and bind and eat. Never has chance to lyse.

Question 9

Is macrophage activated in apoptosis?

Answer 9

NO. phsyiologically silent.

Question 10

Genes in apoptosis

Answer 10

Via radiation experiment with lymphocytes learned that all cells have “death genes”. Therapeutic target!
diff cells have diff triggers.

Question 11

How frequently does apoptosis occur?

Answer 11

Morphogenetic death in embryology. Limbs and brain. At least 1/3 of developing brain cells die.
Need correct target contact.
Immune system! Skin. Villi, cells at tip apoptosed.

Question 12

Cell division and apoptosis are…

Answer 12

matched precisely. 1 death for 1 growth.
mutation causes abnormal growth, will have apoptosis unless also get mutation for apoptosis.
Cancer: mutations in death and growth!

Question 13

Intrinsic pathway

Answer 13

1. ) Perturb mito outer mem fx (normally guarded by anti-apoptotic proteins like Bcl-2). Get death signal and make:
2. ) Pro-apop members (Bim PUMA), they replace anti
3. ) Other mems of family can act on mem
4. ) It becomes permeable and releases cytochrome C into cytoplasm.
5. ) Activate Apaf- caspases. Death via apoptosis.

LESSON: death is controlled by pro and anti-apoptotic factors

Question 14

Extrinsic pathway

Answer 14

Cytotoxic T cells. Instruct cells to undergo apoptosis by 2 mechanisms:
1.) CTP increases surface mlc Fas… blah blah blah adaptor and cascpase death
2.) CTL secrete granzyme/perforin.
Fadd:flip ratio determines life or death.

Question 15

Intrinsic vs extrinsic * memorize

Answer 15

Downstream result is the same.
Effector is caspase 3.
Intrinsic: capsase 9 and 3, mitochondria
Extrinsic: caspase 8 and 3. FADD (yes apoptosis, activates casp 8) and FLIP (no apoptosis)

Question 16

ALPS

Answer 16

cells fail to die (mutation in fas), accumulate lymph cells. Lymphedema.

Question 17

FLIP

Answer 17

competitively binds FADD (instead of caspase) inhibits apoptosis.
Pathogens can steal things like this.

Question 18

Bacteria and FADD

Answer 18

they glycosylate it so it can’t activate caspase, no apoptosis.

Question 19

Better dead than alive?

Answer 19

Lymphocytes are dangerous because they rapidly prolif (autoimmune, lymphoma), so they will not repair but will die.
Decision to repair or die differs between cell types.
Cells more susceptible to malignancy might also resist apoptosis more often.