Mechanisms of Cell Death

Question 1

What causes DNA ladder formation?

Answer 1

Cleavage of DNA at histones, creating a regular pattern of cleavage

Question 2

What is the “morphology” of a disease?

Answer 2

The appearance of cells/tissues/organs

Question 3

Describe the intrinsic pathway of apoptosis.

Answer 3

Mitochondrial signals from within the cell induce release of pro-apoptotic proteins that activate caspases.

Question 4

What are the hallmark characteristics of necrosis (histologically)?

Answer 4

Pyknosis (loss of nuclei)

Breakdown of membranes

Question 5

True or false

The ER stress-induced apoptosis mechanism is fully understood.

Answer 5

False

Question 6

What are the consequences of calcium toxicity within the cell?

Answer 6

ER calcium depletion induces UPR

ER calcium release may activate specific enzymes (Calpain & Calcineurin)

Excessive mitochondrial calcium (releases proapoptotic factors)

Question 7

What type of tissue damage is depicted here?

Answer 7

Calcification

(basophilic deposits)

Question 8

What is Anoikis?

Answer 8

Detachment-induced cell death

Question 9

PIDD = ?

Answer 9

p53-induced death domain

Question 10

Why is the detection of phosphatidylserine an indicator of apoptotic cell death?

Answer 10

It’s a phospholipid normally found on the intracellular side of the cell membrane. It gets externalized during apoptosis.

Question 11

What are the four subfamiles of the death domain superfamily?

Answer 11

Death Domain (DD)

Death Effector Domain (DED)

Caspase Recruitment Domain (CARD) subfamily

Pyrin Domain (PYD)

Question 12

What is necroptosis?

Answer 12

Regulated necrosis

Question 13

How does p53 function?

Answer 13

Transcription factor for:

1. Negative regulators of cell cycle progression
2. Apoptosis promoting genes (Bax & Bak)

Question 14

What type of intracellular accumulation is pictured here? What is it composed of and what tissue is it in?

Answer 14

Lipofuscin (oxidized proteins from cellular components of cells that cannot be broken down)

Cardiac muscle

Question 15

What are the hallmark characteristics of stressed tissue (histologically)?

Answer 15

Blebbing

Eosinophilia

Swelling

Question 16

What is the “pathogenesis” of a disease?

Answer 16

The biochemical and molecular mechanisms of disease development

Question 17

Which caspases are initiator caspases?

Answer 17

2, 8, 9, 10

Question 18

How does the ER participate in death signaling?

Answer 18

Release of ER calcium primes mitochondria to initiate the intrinsic pathway

Question 19

What type of necrosis is pictured here?

Answer 19

Coagulative

Question 20

What type of intracellular accumulation is pictured here? What tissue is it located in?

Answer 20

Fatty deposits

Liver

Question 21

What are some major morphological features of apoptosis? (4)

Answer 21

Cell rounding/condensation

Nuclear condensation/fragmentation

Membrane blebbing

Formation of apoptotic bodies

Question 22

Which caspases are executioner caspases?

Answer 22

3, 6, 7

Question 23

How is caseous necrosis described?

Answer 23

Fragmented cells and granular debris surrounded by inflammation

“Cheese-like” (crumbly)

Question 24

Which caspase is involved in ER stress-induced apoptosis?

Answer 24

Caspase 12

Question 25

What is the "manifestation" of a disease?

Answer 25

Functional consequences of morphological structures.

Question 26

Describe the extrinsic pathway of apoptosis

Answer 26

Death receptors on the plasma membrane are activated and transduce a signal through intracellular signaling pathways to activate caspases

Question 27

The "etiology" of a disease refers to its \_\_\_\_\_.

Answer 27

Cause

Question 28

What type of intracellular accumulation is pictured here?

Answer 28

Protein

Question 29

True or false. Apoptosis is energy-dependent

Answer 29

True

Question 30

What are some apoptotic initiators (8)?

Answer 30

Viral infections Ionizing radiation Chemical damage to cells Cytokines (TNF & Fas) Mitochondrial damage Unfolded protein response Calcium influx Unresolved stress

Question 31

How do caspases function?

Answer 31

Cleave proteins after aspartic acid residues

Question 32

How is fibrinoid necrosis described?

Answer 32

Immune complexes and fibrin in walls of blood vessels

Question 33

What causes stress in the endoplasmic reticulum?

Answer 33

Accumulation of misfolded proteins

Question 34

What is the consequence of overexpression of p53?

Answer 34

Promotes aging

Question 35

How is liquefactive necrosis described?

Answer 35

Digestion of cells resulting in viscous mass

Question 36

What is the function of p53?

Answer 36

Anti-oncogene Critical in DNA damage and repair

Question 37

What is a consequence of decreased expression of p53?

Answer 37

Increased cancersusceptibility

Question 38

What happens if ER stress is not resolved?

Answer 38

ER-stress induced cell death

Question 39

How is coagulative necrosis described?

Answer 39

Loss of cell architecture but not tissue architecture

Question 40

What is homotypic binding?

Answer 40

Binding of death domains to similar death domains Ex: DED binds with other DEDs

Question 41

What type of necrosis is pictured here?

Answer 41

Fibrinoid necrosis

Question 42

What is the unfolded protein response (UPR)?

Answer 42

A stress response that promotes the degradation of proteins and increased chaperone production to improve folding

Question 43

What are four instances of physiological cell death?

Answer 43

Embryogenesis Tissues that produce new cells as their function Loss of hormone-dependent tissues when hormone levels fall Immune function