36 Questions
What is the primary difference between apoptosis and necrosis?
Apoptosis is regulated cell death, while necrosis is accidental cell death.
What is the role of apoptosis in tissue remodeling and development?
To remove excess cells and form mature tissues.
What is a characteristic of necrosis?
Cells die due to lack of ATP or physical damage.
What is the term for the process by which cells die in a controlled manner?
Programmed Cell Death (PCD)
What is the result of apoptosis in terms of inflammatory response?
No inflammatory response is triggered.
What is the term for the process by which cells die due to lack of ATP or physical damage?
Accidental Cell Death (ACD)
What is the result of necrosis in terms of cell contents?
Cell contents are released into the extracellular space.
What is a trigger of apoptosis?
Intrinsic or extrinsic signals.
What is the primary function of iCAD?
Inhibition of CAD endonuclease
What is the result of DNA fragmentation during apoptosis?
Cleavage of DNA in the regions between nucleosomes
What triggers the caspase cascade in the extrinsic pathway?
Binding of Fas ligand to Fas receptor
What is the function of executioner caspases?
Degradation of iCAD
What is the name of the complex formed after the binding of Fas ligand to Fas receptor?
Death-inducing signalling complex (DISC)
What is the name of the receptor family that death receptors belong to?
Tumour necrosis factor (TNF) family
What is the result of caspase degradation of iCAD?
Activation of CAD endonuclease
What is the name of the process triggered from outside the cell?
Extrinsic pathway
What is the primary function of phosphatidylserine in apoptosis?
To facilitate phagocytosis by macrophages
What is the role of survival factors in apoptosis?
They block apoptosis by binding to cell surface receptors
What is the primary function of apoptosis in response to excessive DNA damage?
To prevent the possible development of cancer by removing damaged cells
What is the outcome of caspase activation in apoptosis?
Flipping of phosphatidylserine to the outer leaf of the plasma membrane
What type of radiation induces chemical bonds between adjacent thymines, leading to thymine dimers?
UVB (290-320nm)
What is the consequence of Bax/Bak aggregation?
Activation of caspases
What is the primary function of initiator caspases in the apoptotic pathway?
To cleave and activate executor caspases
Why are survival factors important during development?
They block apoptosis to regulate cell number
What is the result of thymine dimers on DNA structure?
Disruption of DNA structure and interference with accurate replication
What is the importance of phagocytosis in apoptosis?
It removes apoptotic cells to maintain tissue homeostasis
What is the fate of apoptotic cells?
They are engulfed and destroyed by phagocytosis by macrophages
What is the morphological change observed during apoptosis where the cell surface bulges?
Blebbing
What is the role of executor caspases in the apoptotic pathway?
To activate all the changes in cell biology observed in apoptosis
What is the result of excessive DNA damage on skin keratinocytes?
They undergo apoptosis and form 'sunburn cells'
What is the primary mechanism that contributes to the development of cancers?
Increase in cell division or decrease in apoptosis
What is often found at the centre of solid tumours?
A necrotic core due to lack of blood supply
What is the result of a decrease in apoptosis in the development of cancers?
An increase in the number of cells
What is a key factor that regulates the development of cancers?
Survival factors
What is the primary mechanism that leads to the development of solid tumours?
Mutations and subsequent development by further mutations
What is the importance of apoptosis in the development of cancers?
It inhibits the development of cancers
Study Notes
Cell Death
- Apoptosis: Regulated cell death (RCD) or Programmed Cell Death (PCD) where cells die in a controlled way, and their contents are not released, triggering no inflammatory response.
- Necrosis: Accidental cell death (ACD) due to lack of ATP, physical damage, or injury, where cell contents are released, triggering an inflammatory response.
Role of Apoptosis
- In tissue re-modelling and development: Removes excess cells to form mature tissues, e.g., during metamorphosis, limb development, and establishment of the adaptive immune system.
- In removing damaged cells: Prevents cancer development by eliminating cells with excessive DNA damage, such as those exposed to UVB radiation.
Morphological Changes during Apoptosis
- Cells become smaller
- Cytoskeleton collapses
- Nuclear envelope disassembles
- Chromatin condenses and is fragmented
- Cell surface bulges (blebs)
- Cells break up into membrane-bound "apoptotic bodies"
- Apoptotic bodies are engulfed and destroyed by phagocytosis by macrophages
Caspases – Intracellular Mediators of Apoptosis
- A family of proteases that trigger a sequence of intracellular events leading to apoptosis
- Initiator caspases:Inactive monomers in the cytosol that are activated by cleavage during apoptosis
- Executor caspases: Activated by initiator caspases, which then activate all the changes in cell biology observed in apoptosis
DNA Fragmentation
- Activated by caspases, which cleave and activate the endonuclease CAD
- DNA is cleaved in the regions between nucleosomes, resulting in a ladder of fragments
Extrinsic Pathway to Trigger Apoptosis
- Activation of death receptors on the cell surface, such as the Fas receptor
- Binding of Fas ligand to the Fas receptor activates the caspase cascade
Removal of Apoptotic Cell by Macrophage
- Cells undergoing apoptosis are detected and removed by phagocytosis
- Phosphatidylserine (PS) is flipped to the outer leaf of the plasma membrane, triggering phagocytosis
Survival Factors
- Block apoptosis by interfering with Bax/Bak aggregation
- Examples: Bcl2
- Most cells require continuous signalling by survival factors produced by neighbouring cells to block apoptosis
Apoptosis and Cancer
- Cancers are caused by an excessive number of cells due to mutations and decreased apoptosis
- Increase in cell division or decrease in apoptosis can contribute to cancer development
- At the centre of solid tumours, a necrotic core often forms due to a lack of blood supply
Understand the differences between necrosis and apoptosis, and learn about the intracellular pathways involved in these cell death processes. Appreciate the clinical importance of apoptosis.
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