Lecture 7

1.
What is accidental cell death?
"Instantaneous rupture caused by physical, chemical insult, pressure, temperature etc."
2.
What does accidental cell death result in?
"Inflammation, regulated cell death in neighbouring cells"
3.
What are the types of regulated cell death?
"Programmed (physiological) cell death, induced regulated cell death"
4.
When does apoptosis occur?
"During development to remove superfluous, worn out or damaged"
5.
How is apoptosis recoginised?
"Cell rounding, shrinkage, fragmentation. Chromatin condensation (pyknosis), nuclear fragmentation (karyorrhexis)"
6.
What is apoptosis induced by?
"Death ligands (FSL, TNF), loss of survival signals (GFs), homelessness (anoikis), oxidative stress (ROS), DNA damage"
7.
Describe the FADD apoptosis pathway?
FASL > FASR > FADD > Initiator caspases > Executioner caspases
8.
Describe the alternate apoptosis pathway?= ="Apoptotic signals (ROS, decreased GFs, Damaged DNA, ECM (homelessness)) > pores in mitochondrial membrane > cytochrome c release > formation of apoptosome (apoptotic protease activating factor-1), activation of initiator caspases, activation of executioner caspases"
9.
What proteins are inhibited by Smac in the apoptotic pathway?
Inhibitor of apoptosis proteins (inhibit caspases)
10.
What signals are released from apoptotic cells?
"Find me signals (ATP), eat me signals (phosphatidylserine)"
11.
What is the difference between TNF and TGF beta?
"Tumour necrosis factor is pro inflammatory, transforming growth factor beta is anti inflammatory"
12.
"When macrophages phagocytose apoptotic bodies, what happens to their release of TNF and TGFbeta?"
"Release of TNF decreases, release of TGFbeta increases"
13.
When does inadequate apoptosis take place?
"Cancer, autoimmune disease"
14.
When does excessive apoptosis occur?
"Brain and heart infarctions (at margins), chronic heart failure, neurodegeneration, pancreatic islet beta cells in diabetes"
15.
"What happens before, during, after necrosis?"
"Membrane permeability and lysis, release of DAMPs, fibrosis"
16.
When does necroptosis occur?
"When TNF or FasL signal receptor interacting protein kinases to form pores in cell membrane, causing lysis"
17.
18.
Describe how pyroptosis occurs?
Phagocytosed PAMPs activate inflammasomes which signal gasdermin proteins to form pores in cell membrane of phagocytic cell. Activates inflammation and prevents replication of intracellular bacteria
19.
Describe how ferroptosis occurs?
Stress > p53 > supression of GSH > suppression of GPX4 > increase in ROS + Fe which generate lipid peroxides > cell death
20.
Decribe how autophagy causes cell death?
"Phagocytosis of pathogen, proteins into autophagosome > autophagosome fuses with lysosome to form autolysosome. Excessive autoysosome generation leads to cell death "
21.
Where does ischaemia result in necrosis?
"Coagulative (myocardia infarcts), colliquative (stroke), gas gangrene (alpha toxin from Clostridium perfringens), dry gangrene (atherosclerosis)"
22.
When does necrosis follow infection?
"Supporative necrosis (abscesses), caseous necrosis (tuberculosis) "
23.
When does necrosis follow injury?
"Injury to adipose tissue, acute haemorrhagic pancreatitus"