(L5) Initiation of apoptosis

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What type of signals initiate apoptosis?
Internal and external
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What cells do mammals use to destroy damaged or virus-infected cells?
Cytotoxic T lymphocytes (white blood cells)
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What type of signals do white blood cells use?
External signals that stimulate death receptor proteins on the cell surface
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What are the 2 main steps of how cytotoxic T lymphocytes is involved in apoptosis
1) It recognises infected or damaged cells, 2) It activates apoptosis
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How does a cell present the receptor on its surface to be recognised by the cytotoxic T lymphocyte?
Incomplete breakdown of endogenous or foreign proteins in proteasomes producing peptides, which are transported to endoplasmic R and bind to MHC proteins and are exported to cell surface, target cell presents peptide bound to MHC on surface
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What is MHC?
Major histocompatibility complex
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What happens once the proteins bound to the major histocompatibility complex proteins are exposed on the cell surface?
T cell receptor on the cytotoxic T cell binds to peptide and MRC proteins and recognises peptides from pathogen proteins or does not recognise peptides from organisms own proteins (self-tolerance)
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What molecules are the initiators of apoptosis?
Caspase-8 or Caspase-10
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What domain in the procaspases aids in apoptosis?
Death effector domain (procaspases are thee precursors to caspases)
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On target cells, what is on their cell surface which is involved in apoptosis activation?
A death receptor protein, called Fas, which contains an intracellular death domain
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What do cytotoxic T cells (killer lymphocytes) have on their cell surface which binds to Fas?
Fas ligand
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After Fas has blinded to the Fas ligand on the cytotoxic T cell, what happens?
Fas aggregates, procaspase-8 or -10 associates with Fas via an adaptor protein (FADD) to form death-inducing signalling complex (DISC), procaspase molecules then activated each other and initiate further procaspase activation and caspase activation
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What cellular stresses can trigger an internal signal for apoptosis?
Radiation, toxic chemicals, oxidative stress, viral infection
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Which caspase is use as the initiator caspase?
Caspase-9
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What does the prodomain of procaspase-9 contain?
A caspase recruitment domain (CARD)
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Describe the mechanism that activates apoptosis from internal signals
Apoptotic stimulus causes mitochondria to release cytochrome c, which binds to adaptor protein Apaf1, Apaf1 molecules assemble via own CARD domains with cytochrome c form apoptosome, procaspase-9 binds to apoptosome via own CARD and becomes activated
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How does it become activated?
Caspase-9 cleaves and activates procaspase-9, this leads to a caspase cascade leading to apoptosis
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What is Bcl2?
Family of proteins which major role is to control thee release of cytochrome c from the mitochondria
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Other cards in this set

Card 2

Front

What cells do mammals use to destroy damaged or virus-infected cells?

Back

Cytotoxic T lymphocytes (white blood cells)

Card 3

Front

What type of signals do white blood cells use?

Back

Preview of the front of card 3

Card 4

Front

What are the 2 main steps of how cytotoxic T lymphocytes is involved in apoptosis

Back

Preview of the front of card 4

Card 5

Front

How does a cell present the receptor on its surface to be recognised by the cytotoxic T lymphocyte?

Back

Preview of the front of card 5
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