Lecture 21: Cell death via Apoptosis

Question 1

What are some pathological and physiological kinds of apoptosis to occur?
First physiological apoptosis

Answer 1

Physiological:

• development (embryogenesis)
• cell turnover
• tissue involution (breast)
• immune mediated cell killing

Embryology:
-webbing fingers, frog loosing its tadpole tail.
Cyclic atrophy- eg hormonal regression of breast after lactation
-neutrophil death in acute inflammation
Apoptosis is important in cellular turnover as it is balancing mitosis.

Question 2

Pathological apoptosis

Answer 2

Neurodegenerative diseases e.g. Alzheimer’s
Killing of virally-infected cells e.g. hepatitis (useful to body)
n.b. viruses can prevent apoptosis e.g. papillomavirus binds p53 (a pro-apoptotic protein) (harmful to body)
Autoimmune or immune-mediated diseases e.g. graft vs. host disease, tissue rejection
Atrophy e.g. kidney after urinary obstruction
Hypoxic injury, especially in marginal area
Sunburned epidermis
Cells with damaged DNA, detected via p53 (useful to body)
Neoplasia (prevention of apoptosis occurs in tumours)

OFTEN, MILD CELL INJURY (HEAT, RADIATION, HYPOXIA) MAY CAUSE APOPTOSIS, BUT WILL CAUSE NECROSIS IF MORE SEVERE

Question 3

Developmemt of a tumor. How does this relate to apoptosis?

or development of atrophy?

Answer 3

-there is increased cell production (mitosis) and decreased cell death (apoptosis)
slide 10

Atrophy?
-decreased cell production and increases cell death

Question 4

Apoptosis vs (oncotic) Necrosis
12

Answer 4

APOPTOSIS

• Typically single cells
• Cell shrinks
• Chromatin condenses & nucleus fragments
• Cell mb. intact
• Cytoplasm in apoptotic bodies
• No inflammation - phagocytosis of apoptotic bodies: rapidly cleared
• Active process
• Can be physiological

NECROSIS (Necrosis is death of body tissue. It occurs when there is not enough blood flowing to the tissue,)

• Often affects group/field
• Cell swells
• Nuclear lysis
• Cell mb. damage
• Cytoplasm released

-Often inflammatory
-May be slow to clear
-Not energy-dependant
-Always pathological

Question 5

Check out the morphology on slide 15

explain it

Answer 5

This EM shows also how the nucleus in apoptosis shrinks and condenses, as shown in the middle image. 
With necrosis (right) the nucleus often swells and the cell membranes break down.

Question 6

Check out slide 18 of signalling apoptosis

Answer 6

Example for PUSH (a positive trigger): anticancer therapy forcing apoptosis in tumour cells only
Example for PULL (withdrawal of a signal, i.e. a hormone, growth factor): AIDS when depletion of T lymphocytes occurs

Question 7

What is the process

slide 19

Answer 7

1. Signalling pathway - Receptor-mediated, other stimuli (PUSH), or withdrawal of hormones/growth factors (PULL)
2. Control & integration – Adapter proteins transmit signal to execution mechanism, or bcl-2/bax family of proteins regulate mitochondrial permeability
3. Execution – Initiator (8, 9) & executioner (3) caspase activation (cysteine proteases) causes protein hydrolysis of cytoskeleton, and triggers endonucleases
   - Protein cross-linkage
   - Endonucleases chop DNA into 200 bp fragments (see DNA gel “ladder”)
4. Dead cell removal - Phagocyte receptors expressed

Question 8

Process:

1. Receptor-mediated (extrinsic or death receptor pathway)

Answer 8

20

few more slides to add dbf