31.1 Necrosis and Apoptosis Flashcards
What are the main forms of RCD (regulated cell death)/programmed cell death?
- Apoptosis
- Necrosis
- NETosis
- Pyroptosis
What is apoptosis?
- ‘Programmed’ cell death directed by the expression of specific genes.
- no inflammation is produced.
Summarise the two main pathways of apoptosis.
Intrinsic pathway:
- Non-receptor mediated: Various stimuli (e.g. DNA damage) lead to eventual release of cytochrome c from mitochondria
- Activates caspases
- Leads to cell death
Extrinsic pathway:
- Receptor-mediated: Stimulation of death receptors by death receptor ligands leads to signalling cascade
- Activates caspases
- Leads to cell death
Think of the caspase as the common end goal of these pathways. They can either be triggered by ligands that bind to receptors, or some sort of cell damage (or other change) which lead to release of cytochrome c from mitochondria.
What are some of the roles of apoptosis?
- Normal tissue homeostasis
- Embryonic morphogenesis
- Deletion of self-reactive lymphocytes
What are some things that can trigger the intrinsic apoptotic pathway?
- It can be developmentally programmed
- Lack of a specific growth factor
- Unrepaired DNA damage
What are some things that can trigger the extrinsic apoptotic pathway?
- TNF-α activating the TNF receptor
- FAS ligand activating the FAS receptor
- Cytotoxic T-cell granule release
How is apoptosis regulated?
The common end to the intrinsic and extrinsic pathways of apoptosis are the executioner caspases. These are under the control of various mitochondrial regulators.
How does apoptosis actually happen (mechanistically)?
- The executioner caspases lead to endonuclease activation (leading to degradation of DNA) and catabolism of the cytoskeleton.
- DNA fragments and organelles are packed into cytoplasmic buds (blebbing), known as apoptotic bodies, which are dealt with by macrophages (without release of inflammatory mediators)
What is necrosis?
- Necrosis is a form of irreversible cell injury that leads to cell death by autolysis (self-digestion).
- It is usually caused by external factors, such as trauma.
Compare apoptosis and necrosis.
Apoptosis:
- Controlled
- Cells play an active role (cell suicide)
- Does not lead to cell lysis and release of inflammatory mediators
Necrosis:
- Uncontrolled
- Cells are more passive
- Leads to cell lysis and release of inflammatory mediators
Compare the difference in morphology seen during apoptosis and necrosis.
Give some examples of the different types of necrosis.
- Liquefactive necrosis -> Cell structure is destroyed by digestion, leading to the formation of a viscous liquid mass
- Coagulative necrosis -> Cell structure is intact, but there is coagulation due to to protein degradation, where albumin tranforms into a firm state.
- Caseous necrosis -> A combination of coagulative and liquefactive necrosis, with incomplete digestion leaving behind granular particles.
- Fat necrosis -> Associated with acute pancreatitis.
What happens following necrosis?
There is release of inflammatory mediators, which can attract phagocytes, etc. However, these can lead to damage of surrounding tissue, so that the process is renewed and is self-reinforcing.
What is pyroptosis?
Controlled form of cell necrosis.
*It is activated by caspases and caspase-mediated cleavage of gasdermin-D.
How does pyroptosis differ from necrosis?
- Necrosis is caused by physical or mechanical tissue injury -> It is not controlled.
- Pyroptosis is carried out in a deliberate and highly self-programmed process that generally involves innate immune cells and activation of inflammasomes.
