L3 - Mechanisms of Disease: Cell damage + death

Question 1

What is the function of Necrosis?

Answer 1

To remove damaged cells from an organism.
Failure to do so may lead to chronic inflammation.
Necrosis causes acute inflammation to clear cell debris via phagocytosis

Question 2

What are the causes of Necrosis?

Answer 2

Injury
Infarction
Infection
cancer
inflammation

Question 3

Describe the process of Necrosis?

Answer 3

• lack of oxygen prevents normal glycolysis and ATP production
• ATP is required for ion pumps of cells to work. Without it cells swell due to influx of water
• Increased pressure within the cell causes lysosomes to rupture. Enzymes degrade other organelles and nuclear material
• cellular debris is released and it triggers inflammation

Question 4

Describe the nuclear changes during necrosis?

Answer 4

• chromatin condensation and shrinkage
• fragmentation of nucleus
• dissolution of chromatin by DNAse

Question 5

Describe the cytoplasmic changes during necrosis?

Answer 5

• Opacification (protein denaturation and aggregation - turns from clear to white)
• cell liquifies

Question 6

What is of apoptosis?

Answer 6

Selective process for the deletion pf superfluous, infected or transformed cells.

Question 7

What is the function of apoptosis?

Answer 7

• embryogenesis
• metamorphosis
• normal tissue turnover
• endocrine dependent tissue atrophy
• pathological conditions

Question 8

Describe the process of Apoptosis?

Answer 8

• cells shrink as the cytoskeleton is disassembled.
• orderly packaging of organelles and nuclear fragments into membrane bound vesicles
  new molecules are expressed on vesicle membranes which stimulate phagocytosis without the inflammatory response.

Question 9

Describe the cytoplasmic changes during apoptosis that can be viewed via a microscope?

Answer 9

• shrinkage of the cell
• cell fragmentation
• phagocytosis of fragments by macrophages
• no leakage of cytosolic components

Question 10

Describe the nuclear changes during apoptosis that can be viewed via a microscope?

Answer 10

• chromatin condenses on nuclear membrane

- DNA cleavage

Question 11

Describe the biochemical changes during apoptosis?

Answer 11

• expression of charged sugar molecules on outer surface of cell membranes (recognised by macrohages)
• cleavage of proteins via proteases

Question 12

What are Capsases?

Answer 12

They are the point of convergence for all causes of apoptosis
they are cysteine protease enzymes that act as primary effectors of apoptosis.

Question 13

How do caspases work?

Answer 13

They form an activation cascade, where one cleaves and activates the next caspase

Question 14

What are initiator and effector caspases?

Answer 14

Initiator - start the cascade

effector - have other substrates and effects too.

Question 15

What is the process of extrinsic apoptosis?

Answer 15

induced by ligand binding to receptors, causing receptor dimerisation.

TNF:

• TNF binds to TNFR, which brings the death domains in close proximity with each other.
• This causes dimerisation with other proteins containing the death domain (FADD).
• FADD also contains death effector protwins at the bottom, so it brings the death effector domains within close proximity.
• This causes the binding of procaspase 8
• A multi-protein complex has now been formed which is called -DISC (death inducing signalling complex).
• Autoproteolysis of caspases occurs and it goes onto induce the caspase cascade in cytoplasm.

Question 16

What is the process of intrinsic apoptosis?

Answer 16

• induced by cytochrome c released from mitochondria
• cytochrome c is a mitochondrial mayrix protein, released in response to oxidative stress as a permeability transition - which eventually induces apoptosis.

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Question 17

What are the 2 types of BCL-2 proteins and what are their functions?

Answer 17

ANTI-APOPTOTIC (bcl-2, bcl-xl etc) - repress cytochrome c release

PRO-APOPTOTIC (bax, bad, bid etc) - facilitate cytochrome c release