Lecture 5 Flashcards
What are the 5 types of cell death?
Oncosis/Necrosis, Necroptosis, Pyroptosis, Apoptosis, Autophagic Cell Death
What occurs in oncotic cell death?
The cell loses control of the composition of its ions due to trauma resulting in swelling causing lysis and cell death resulting in inflammation
What occurs in Necroptosis?
Death ligands activate receptors which turn on protein kinases RIP 1/3 causing mitochondrial dysfunction leading to a build up in reactive oxygen species resulting in lipase activation and messy cell death
What is tumour necrosis factor?
A death ligand
What is a necrostatin?
A competitive inhibitor for RIP 1 protein which can be used to suppress inflammation
What occurs in pyroptosis?
Bacterial products activate the inflammasome, which activates the caspase-1 protease resulting in cell lysis and inflammation
What is an inflammasome?
An internal danger sensor of cells causing inflammation ad cell death
What is the purpose of pyroptosis?
To product against the intracellular replication of bacteria and to alert the immune system to the presence of invaders
What occurs in apoptosis?
This is a more natural and clean way of removing cells that are old and need to be turned over, or if they are in excess to requirements. This is a process which retains an intact cell membrane stopping inflammation provided the budding off apoptopic bodies are phagocytosed before they degrade
What occurs in Autophagic cell death?
Double membrane vacuoles enclose cytoplasm or organelles to form autophagosomes, these then fuse with a lysosome to form an autolysosome
What is the normal purpose of autophagy?
To remove misfolded proteins and damaged organelles but the process can result in cell death if the cell is placed under tooo much stress
In the case of anoxia what is the mechanism of oncosis? (Hint there are 9 steps)
- Reduced ATP results in failure of the Na/K ATPase causing build up of Na+
- Use of glycosis due to lack of Oxygen results in increase in lactic acid and a decrease in intracellular pH
- The Na/H exchange is activated to restore pH but this results in an even higher conc. of Na+
- Na+ Concentration is reduced through a Na+/Ca2+ transporter resulting in accumulation of Ca2+
- Due to a lack of ATP the Ca2+ pump can not remove Ca2+
- High Ca2+ conc. activates phospholipases releasing lysophospholipids and fatty acids that damage the cell membrane
- Ca2+ acitvates proteases destroying the cytoskeleton
- The cell lyses
- The spilled contents induce inflammation
What are the 5 causes of apoptotic death?
Engagement of a death ligand with is receptor, Damage to DNA, Absence of required growth factors, Anoikis, Stresses that activate p53
What is Anoikis?
When a call loses its attachment to the extracellular matrix
What does both DNA damage and death ligands activate?
Apoptotic Caspases
What is the effect of an apoptotic caspase?
Pores are opened in the outer mitochondrial membrane releasing Cytochrome C, Apoptotic protease activating factor and a caspase casade
What are Caspases?
Proteases activated by oligomerisation and proteolytic cleavage, which cleaves proteins after any aspartate residue resulting in apoptosis
What are the signals that apoptotic cells release?
Find me ATP signal and eat me Phosphatidylserine on the outside of the cell
What do phagocytosing cells express after ingesting an apoptotic body and what is its function?
Phosphatidylserine which supresses the release of the inflammatory protein Tumour Necrosis Factor and releases the anti-inflammatory protein transforming growth factor
What can result from a loss of normal apoptosis?
Cancers and autoimmune diseases as lymphocytes which target ‘self’ are not removed
What is the result of excessive apopotosis?
ischaemic injury, heart failure, neure degeneration, beta pancreatic cells in diabetes, lymphocytes in AIDs
What are four types of necrotic lesions?
Coagulative necrosis, Colliquative necrosis, gas gangrene and dry gangrene
What is Coagulative Necrosis?
Dead tissue is firm, retain its initial shape until removed by inflammatory cells and replaced with scar tissues. This can result in lesions that persist for years due to inaccessibility
What is Colliquative necrosis?
Occurs when a cerebral blood vessel has been blocked, which results in digestion of brain tissue and cyst being formed by glial cells
