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Questions and Answers
What is the primary difference between apoptosis and necrosis?
What is the role of apoptosis in tissue remodeling and development?
What is a characteristic of necrosis?
What is the term for the process by which cells die in a controlled manner?
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What is the result of apoptosis in terms of inflammatory response?
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What is the term for the process by which cells die due to lack of ATP or physical damage?
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What is the result of necrosis in terms of cell contents?
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What is a trigger of apoptosis?
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What is the primary function of iCAD?
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What is the result of DNA fragmentation during apoptosis?
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What triggers the caspase cascade in the extrinsic pathway?
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What is the function of executioner caspases?
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What is the name of the complex formed after the binding of Fas ligand to Fas receptor?
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What is the name of the receptor family that death receptors belong to?
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What is the result of caspase degradation of iCAD?
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What is the name of the process triggered from outside the cell?
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What is the primary function of phosphatidylserine in apoptosis?
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What is the role of survival factors in apoptosis?
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What is the primary function of apoptosis in response to excessive DNA damage?
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What is the outcome of caspase activation in apoptosis?
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What type of radiation induces chemical bonds between adjacent thymines, leading to thymine dimers?
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What is the consequence of Bax/Bak aggregation?
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What is the primary function of initiator caspases in the apoptotic pathway?
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Why are survival factors important during development?
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What is the result of thymine dimers on DNA structure?
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What is the importance of phagocytosis in apoptosis?
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What is the fate of apoptotic cells?
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What is the morphological change observed during apoptosis where the cell surface bulges?
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What is the role of executor caspases in the apoptotic pathway?
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What is the result of excessive DNA damage on skin keratinocytes?
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What is the primary mechanism that contributes to the development of cancers?
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What is often found at the centre of solid tumours?
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What is the result of a decrease in apoptosis in the development of cancers?
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What is a key factor that regulates the development of cancers?
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What is the primary mechanism that leads to the development of solid tumours?
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What is the importance of apoptosis in the development of cancers?
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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
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Description
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.