Cell death

Question 1

Describe characteristics of necrosis

Answer 1

• Loss of membrane integrity
• Induces inflammation and repair
• Often affects solid mass tissue
• Always pathological
• Bioenergetic failure

Question 2

What are the causes of necrosis?

Answer 2

• Ischaemia
• Metabolic
• Trauma

Question 3

Coagulative necrosis

Answer 3

• Most tissues
• Firm, pale area
• Ghost outlines on on microscopy

Question 4

Colliquative necrosis

Answer 4

• In the brain

* Liquified

Question 5

Caseous necrosis

Answer 5

• Tuberculosis
• Pale yellow
• Semi solid

Question 6

Gangrene

Answer 6

• Necrosis with putrefaction
• Follows vascular occlusion
• In certain infections it is black

Question 7

Fibrinoid necrosis

Answer 7

• Microscopic feature in malignant hypertension

Question 8

Fat necrosis

Answer 8

• May follow trauma and cause a mass

* May follow pancreatitis visible as white spots

Question 9

Describe the characteristics of apoptosis

Answer 9

• FRAGMENTATION
• DNA fragmentation
• Extrinsic or intrinsic
• ICAD, PARP

Question 10

What are examples of apoptosis?

Answer 10

• Embryology
• Menstrual cycle
• Inflammation
• Immune defence
• Tumour prevention
• Autoimmune disease
• HIV and AIDs

Question 11

How is the debris from apoptosis gotten rid of?

Answer 11

• Reorganisation of phosphatidylserine

* Recognition by macrophages and non-professional phagocytes

Question 12

What happens if the debris from apoptosis is not cleared?

Answer 12

Secondary necrosis

Question 13

Describe extrinsic apoptosis

Answer 13

• Receptor mediated:
- TNF (macrophage produced)
- Fas CD95
• Associated with inflammation and the immune response
• Cytoplasmic signals
• Cause caspase cascade which is then amplified

Question 14

Describe T cell mediated apoptosis

Answer 14

• T cell binds 
• Granzymes release into the cell
• Caspase 10 activated
• Apoptosis 
- Viral infection
- transplant rejection

Question 15

Describe intrinsic apoptosis

Answer 15

• Endogenous activation 
• p53 is the critical determinant 
• Mitochondrion is the key regulator
- Becomes leaky = first step
- Releases cytochrome C 
- Caspases activated

Question 16

What is an apoptosome?

Answer 16

• Involved in the signalling phase of apoptosis

* Activated by cytochrome C

Question 17

What is the effect of p53 in apoptosis?

Answer 17

• Stops the cell cycle via activation of p21

* Induces apoptosis by increasing the amount of Bax

Question 18

What is the Bcl2 family?

Answer 18

• Form dimers
• Upregulated by p53
• Pro-apotopic

Question 19

Describe the effect of different Bcl2 family homodimers

Answer 19

• Bcl2 + Bcl2 = anti-apoptotic

* Bax+Bax= apoptotic

Question 20

Describe IADs

Answer 20

• Inhibitors of apoptosis

* Means that apoptosis only occurs if the signal is strong i.e. there is a lot of damage

Question 21

In which cases does apoptosis go wrong?

Answer 21

• Autoimmune disease
• Cancer
• Neurodegeneration

Question 22

Which pathway components can be targets for drugs?

Answer 22

• Bcl2 in lymphoma
• Caspase 3 in Alzheimer disease
• IAP in cancer

Question 23

Describe pyroptosis

Answer 23

• Microbial trigger- salmonella
• Pattern recognition receptors NOD like and Toll like
• Caspase 1 not caspase 3
• Nuclear fragmentation but not cytoplasmic blobbing
• Pro-inflammatory

Question 24

What is Anoikis?

Answer 24

Death after losing contact with the basement membrane/extracellular matrix
• Apoptosis morphology