Apoptosis, autophagy and necrosis

What is senescence?

What process in somatic cells is key for senescence?

In healthy adults, cell death usually perfectly balances what?

Billions of intestinal epithelial cells die every hour. How often is the entire gut epithelium replaced?

Why is it significant that the cells that undergo the most wear and tear from the environment, such as intestinal epithelial cells, undergo the most rapid turnover?

Why is apoptosis important in embryological development?

Why is apoptosis important in tissue homeostasis?

Why is apoptosis important in neoplastic disease?

Describe the general process of apoptosis.

What are the two pathways that can result in apoptosis?

Which receptors provide the major mechanism for the extracellular control of apoptosis?

Describe the death receptors involved in the extrinsic apoptotic pathway.

Describe the Fas death receptor.

The binding of the Fas ligand to the death domain of its transmembrane receptor activates which intracellular protein on the intracellular portion of the receptor?

Once FADD is activated by Fas, what protein does its death effector domain recruit?

Once the precursor of caspase-8 has been recruited by the death effector domain of FADD in the extrinsic apoptotic pathway, what protein self-cleaves to activate itself, which is also the last point in the apoptotic pathway that apoptosis can be stopped?

After caspase-8 is activated, describe the rest of the events in the extrinsic apoptotic pathway.

What are caspases and what do they do?

What are the Bcl-2 proteins and what do they do?

What are survival factors required for?

How do survival factors tend to act on cells?

Give four examples of stimuli that can cause the intrinsic apoptotic pathway to be activated.

Cellular damage results in the activation of which gene?

Once activated, what does the p53 gene do?

What function do Bcl-2 proteins have in common with bacterial toxins?

List the events of the intrinsic apoptotic pathway (the 'cellular stress' pathway).

Compare and contrast the extrinsic and intrinsic apoptotic pathways.

What is 'looting' in apoptosis?

What happens to apoptotic bodies other than looting?

Why is the inflammatory response not initiated in apoptosis?

Why do cells become small and rounded in apoptosis? What does this result in?

What is 'blebbing' and why does it occur?

What are apoptotic bodies?

Describe some of the intracellular events during apoptotis.

Describe an oncogene that is involved in the regulation of apoptosis.

Describe a tumour suppressor gene involved in the regulation of apoptosis.

Why might one need to discriminate between apoptotic and necrotic cell death?

What is the method for carrying out a cell viability test to differentiate between apoptosed/necrosed cells and living, healthy cells?

What will be SEEN in apoptosed and necrosed cells in a cell viability test?

What are the benefits of using a cell viability test, rather than any other method, to determined whether cells are alive or necrotic/apoptotic?

What is the method for the terminal d-UTP 'nicked-end' labelling (TUNEL) assay for determining whether cells are alive or apoptotic/necrotic?

What will be SEEN in a terminal dUTP nicked-end labelling (TUNEL) assay to determine whether cells are alive or necrotic/apoptotic? Why might this test not be ideal?

What is the mechanism behind the Apoptest™?

What is seen when the Apoptest™ is used to detect apoptosis?

What is seen if the Apoptest™ is used to detect necrosis?

What is the method behind DNA fragmentation/laddering for testing for apoptotic/necrotic cells?

What is seen on the agarose gel in a DNA fragmentation/laddering test when apoptotic cells are present?

What is seen on the agarose gel in a DNA fragmentation/laddering test when necrotic cells are present?

What is autophagy?

Autophagy uses lysosomes. Describe the contents of a lysosome.

How are organelles taken up into lysosomes in autophagy?

Why can autophagy be seen primarily as a survival mechanism rather than a death mechanism?

What is the name of the 'structure' formed when sections of double membrane begin to form around organelles marked for autophagy?

What protein links the double membrane from a phagophore together to form a more established autophagosome?

What is the name of the structure formed when a lysosome fuses with an autophagosome?

What happens to the LC3B proteins which link the double membrane of the autophagosome together when the autophagosome has fused with a lysosome to form an autolysosome?

What are the products of autophagy?

In which programmed cell death process are phagocytes involved?

In which programmed cell death process(es) is there cell membrane 'blebbing'?

In which programmed cell death process(es) is DNA laddering seen?

In which programmed cell death process(es) are organelles preserved in vacuoles?

In which programmed cell death process(es) is the cytoskeleton preserved?

In which programmed cell death process(es) are caspases involved?

Why is apoptosis a target for treatment and prevention of cancer?

What property, other than being safe, do apoptosis targets in cancer treatment/prevention have?

Why are some cancers reduced in people who habitually take aspirin?

Why might butyrate be able to be used to target gastrointestinal neoplasms?

What is necrosis?

What are the initial, reversible cell changes in necrosis?

If a noxious stimulus persists beyond the reversible changes in necrosis, how does necrosis persist and cause inflammation?

List the seven types of necrosis.

What are the two overall categories of damage that can cause necrosis?

What can cause membrane damage to the point of necrosis?

What can cause mitochondrial damage to the point of necrosis?

What is pyknosis?

What is karyorrhexis?

What is karyolysis?

How do cells appear histologically when undergoing pyknosis?

How do cells appear histologically in karyorrhexis?

How do cells appear histologically in karyolysis?

What is coagulative necrosis?

How long might coagulative necrosis persist?

What is the 'snapshot' situation in coagulative necrosis?

How does liquefactive necrosis predominately differentiate from coagulative necrosis?

What are the two circumstances in which liquefactive necrosis develops?

How might the immune response to a bacterial infection result in liquefactive necrosis?

How might cerebral artery occlusion result in liquefactive necrosis?

How long might the liquefactive necrotic cavity of fluid and necrotic debris (as a result of cerebral artery occlusion) persist?

What may necrosis following ischaemia also be a result of (other than damaged central nervous system cells leaking hydrolases)?

What is caseous necrosis typically caused by (and what is it classically a lesion of)?

Grossly, how does the tissue appear in caseous necrosis?

Why can caseous necrosis be considered a cross between liquefactive and cogulative necroses?

What is the appearance of the dead cells that persist indefinitely in caseous necrosis?

What is present in the centre of a tuberculous granuloma?

In what tissue does fat necrosis occur (only)?

What does fat necrosis typically result from?

Why can fat necrosis follow pancreatitis or pancreatic trauma?

Why is necrotic fat recognised early?

What forms the palpable lump in fat necrosis?

Where does fibrinoid necrosis most commonly occur?

What does the term 'fibrinoid necrosis' describe?

What is deposited in the damaged blood vessels in fibrinoid necrosis? What classes this injury as necrotic?

What does the word 'gangrene' describe?

If liquefactive necrosis can be called wet gangrene, what can gangrene be called?

Where is gangrene most commonly seen?

How does one characterise dry and wet gangrene?

Where is autolytic change/autolytic necrosis most commonly seen?

In autolytic necrosis, enzymes leak from the cells and digest adjacent structures. Why is there no transport or inflammatory response?

What is a characteristic cellular feature in coagulative necrosis?

What is a characteristic cellular feature of liquefactive necrosis?

What is a characteristic cellular feature of caseous necrosis?

What is a characteristic feature of fat necrosis?

What is a characteristic cellular feature of fibrinoid necrosis?

Cells tend to keep Ca2+ out when alive so once they have been killed they lose this ability and there is a large influx of calcium. What does this combine with once in the cell?

Why might there be extracellular calcium deposition in necrotic tissues? Why might this be dangerous?

What distance must a tumour cell be within from a blood supply in order to avoid autophagy/necrosis?

Why can necrosis be an early indicator of cancer?

What is Avastin and how is it used in cancer treatment?

How might one detect calcification in necrosis?

How does the inflammation from necrosis promote survival in neoplastic cells?

Which form of cell death requires energy from the cell?

Which process of cell death usually generates an inflammatory reaction?

Which form of cell death happens to groups of cells rather than individual cells?

In which form of cell death is there cell swelling/shrinkage? Why?

What is the overall cause for apoptosis? And for necrosis?