Cell Death Flashcards
What are the differences between necrosis and apoptosis?
Necrosis produces an inflammatory response as cells burst and toxins leak out where as Apoptosis is carried out in a controlled manner without inflammation.
What are some key things that lead to apoptosis?
Embryology - lumen of tubes (via apoptosis)
Response to growth signal- menstrual cycle (via apoptosis)
Inflammation - resolution, death of neutrophils (via apoptosis)
Immune defence - T and Natural Killer cell responses. (via apoptosis)
Tumour prevention - prevent mutation (via apoptosis)
Autoimmune disease - self destruct (via apoptosis)
HIV AIDS - HIV and activated T cell death (via apoptosis)
What is the role of the Bcl2 family ?
They are involved in check and balances
BCL2 travels in pairs (homodimerise - 2 molecules travelling together that are the same) - The 2 BCL2 prevent cell death
Another member of the family is BAX also travel in a homodimerise fashion but they promote cell death. (they do this by triggering the intrinsic apoptotic pathway).
Cell dies or lives depending on the balance of this family.
How did caspases get their name ?
Caspases are key mediators
They get their name from;
• cysteine in the active site : “C”
• cleavage after aspartate: “asp”
• protease: “ase”
Define anoikis ?
An epithelial cell dies after losing contact with basement
membrane/extra cellular matrix
Can cause a tumour to spread as if it gains the ability to not require a basement membrane then it can travel and form a tumour.
Define pyroptosis ?
Pyroptosis is where skin cells die by losing their nucleus and retaining their keratin.
Its a little like some apoptosis and some necrosis caused by the microbial trigger Salmonella
Pyrop - means fever
What can caspases target?
- cleave ICAD -> destroy genetic information
- cleave PARP -> prevent DNA repair
- cleave lamin -> break down nuclear architecture
- cleave keratin -> break down cytoplasmic architecture
Why are apoptotic cells phagocytosed?
Apoptotic cells are phagocytosed primarily to prevent secondary necrosis, which can trigger inflammation and tissue damage if apoptotic cells are not promptly cleared.
Additionally, phagocytosis of apoptotic cells induces immune tolerance by efficiently processing cellular contents in a non-inflammatory manner, dampening immune responses, and promoting tissue repair.
Overall, phagocytosis of apoptotic cells is crucial for maintaining tissue homeostasis, preventing inflammation, and inducing immune tolerance.
What is reversible cell injury ?
Reversible cell injury is a cell losing its ability to homeostasis but it has not died yet
What conditions to doctors work to save reversible cell injury and why is this important ?
In patients who have had stroke and heart attacks you have killed some cells but you have some cells around that which are sub-lethally injured and you can save them and reverse some symptoms
What toxin is produced from the electron transport chain ?
Oxygen becomes reactive due to electrons producing free radicals (O2-). These free radicals then become Hydrogen Peroxide (H2O2) which is damaging to cells.
What can free radicals cause?
Sublethal/leathal injuries to cells.
What happens in cells that have underwent lethal injury ?
Cells that experience lethal injury break normal homeostasis and necrosis occurs.
Seen in stroke and heart attacks as cells cannot produce energy and die.
How can a thrombus cause lethal injury ?
A thrombus prevents oxygenated blood from reaching Glycolysis in a cell and this causes Anaerobic glycolysis.
In anaerobic glycolysis a little ATP is made but so is Lactate which goes through a series of processes and activates phospholipases, which causes cell membrane damage, leading to cell necrosis.
What is Necrosis?
Necrosis is a complete loss of energy balance in a cell.
It is the death of tissues following bioenergetic failure and loss of plasma membrane integrity
It induces inflammation and repair due to toxins being outside the cell which aren’t wanted
Caused by ischaemia, metabolic, trauma
What is the difference between programmed cell death and apoptosis ?
Programmed cell death is an intention where as Apoptosis is a morphology (fragmentation and budding of cells).
What can we target in cancer chemotherapy to influence life or death of cells?
ICAD (Inhibitor of caspase activated DNase)
PARP (Poly ADP-RIbose polymerase)
How are apoptotic membranes removed and how is a apoptotic cell recognised?
Apoptotic cells (once they have fragmented) flip the lipids in their membrane (reorganisation of phosphatidylserine), which allows macrophages to recognise their phosphotidylserine signal and phagocytose them without an inflammatory response.
Explain what happens in the extrinsic apoptotic pathway?
The 3 main triggers of extrinsic apoptosis is TNF family, Fas CD95 and inflammation.
A trigger factor outside the cell like TNF binds to a TNF receptor (TNFR) in the cell membrane and causes a docking protein to bind to the transmembrane receptor and get activated. This binds to and activates procaspase 8 which becomes caspase 8 once activated. This activates procaspases 3, 6 and 7 to become caspase 3, 6 and 7 which activate Endonucleases (by PARP), nuclear proteins (by Laminators) or Cytoskeletal proteins (by a-fodrin). All of these result in apoptosis of a cell.
The key features in this process is; receptor interaction, cytoplasmic signals and caspase cascade
What happens in a T cell mediated response?
T cells directly hit the target cell
T cells engage with receptors which can induce extrinsic apoptosis
T cells also inject Perforin into the cell which activates the caspase enzymes
Both of these cause fragmentation of DNA and the breakdown of cytoskeleton and cell breaks up into apoptotic bodies to be removed.
This is an extrinsic response
Explain what happens in the intrinsic apoptotic pathway?
Mitochondria becomes leaky then the products it may leak are very harmful to cells (i.e calcium and oxygen radicals)
Cytochrome C is released from the mitochondria which activates the caspases and caspase 3 is the final effector which causes the fragmentation of DNA and the breakdown of cytoskeleton and cell breaks up into apoptotic bodies to be removed.
What is an apoptosome?
Theapoptosomeis a large quaternary protein formed in the process of apoptosis.
Its formation is triggered by the release of cytochrome c from the mitochondria in response to a stimulus.
Cells are in balance so apoptosome concentrate the pro-apoptotic components to outcompete the effects of the normal suppressor components to cause cell death.
What can abnormal BCL2 cause?
Abnormal BCL2 causes cancers as too much BCL2 will cause homdimerisation of BCL2 triggering anti-death signals (cells won’t die).
Difficult to treat these slow growing cancers
How does a lower intake of calories lower the risk of cancers?
Lower calorie intake causes a lower oxidative stress which reduces the likelihood of Apoptosis happening.
