Cell Death Flashcards
What is necrosis?
Dearth of tissues following bioenergetic failure and loss of plasma membrane integrity
What does necrosis induce?
Inflammation and repair
What may cause necrosis?
Ischaemia, metabolic causes, trauma causes, amongst others
What kind of necrosis is seen in the brain?
colliquative necrosis - liquifaction
What necrosis occurs in most types of tissues?
Coagulative necrosis - firm pale area with outline in microscopy
What necrosis occurs in tuberculosis?
Caseous necrosis - pale yellow semi solid material
What is gangrene?
Necrosis with putrefaction - follows vascular occlusion or certain infections and is distinctively black
What necrosis occurs as a microscopic feature in arterioles in malignant hypertension?
Fibrinoid necrosis
What us fibrinoid necrosis?
Fibrinoid necrosis occurs as a microscopic feature in arterioles in malignant hypertension
What necrosis may follow trauma and cause a mass, or follow pancreatitis and be visible as multiple white spots?
Fat necrosis
What does fat necrosis occur after?
Trauma as a mass
Pancreatitis as multiple white spots
How may necrosis be identified microscopically?
Cell go splat
What are the different types of necrosis?
Coagulative Colliquative Caseous Gangrenous Fibrinoid Fat necrosis
When may apoptosis occur?
- Embryology – lumen of tubes
- Response to growth signals – menstrual cycle
- Inflammation – resolution, death of neutrophils
- Immune defence – T and Natural Killer cell responses
- Tumour prevention – prevent mutation
- Autoimmune disease – self destruct
- HIV AIDS – HIV and activated T cell death
What is the difference between the action of necrosis and apoptosis on DNA?
Apoptosis usually involves DNA fragmentation
What general rule is used t differentiate apoptosis and necrosis, especially on microscopy of effected cells?
Necrosis go SPLAT
Apoptosis - think fragmentation
What does the clearance of apoptotic cells by macrophages first require?
Reorganisation of phosphatidylserine - In apoptotic cells PS moves from the inside layer of the phospholipid bilayer to being found predominantly on the extracellular surface and thus may be recognised by macrophages
What are the tow types of ways that apoptosis can be induced?
Extrinsic pathway
Intrinsic pathway
What are some examples of the extrinsic causes of apoptosis?
Receptors
T cells
What are some examples of the intrinsic causes of apoptosis?
– Stress
– Metabolic
– DNA damage and p53
What are the key features of the extrinsic pathway of apoptosis due to receptor action?
Receptor interaction
Cytoplasmic signals
Caspase cascade
What may cause the extrinsic pathway of apoptosis due to receptor action?
TNF family
Fas CD95
Inflammation
What are the key features of the T cell mediated extrinsic pathway of apoptosis?
Perforin and granzymes Cytoplasmic activation
What may cause the T cell mediated extrinsic pathway of apoptosis?
Viral infection
Transplantation rejection
What are the key features of the intrinsic pathway of apoptosis?
Endogenous activation Mitochondrial involvement
Cytochrome C is key
What is a notable key step in the intrinsic pathway of apoptosis?
Release of cytochrome c from mitochondria
What is apoptosome?
The apoptosome is a large quaternary protein structure formed in the process of apoptosis. Its formation is triggered by the release of cytochrome c from the mitochondria in response to an internal or external cell death stimulus
When the procaspase-9 within the apoptosome is activated a caspase cascade occurs which leads to apoptosis
How may radiation cause apoptosis?
Radiation can cause DNA damage to the p53 gene, thus leading to a release of activated p53
This can interfere with the checkpoints of the cell cycle, but also leads to an increased [Bax] which causes the MPTP of the mitochondrion to open when it outweighs [Bcl-2] and so apoptosis occurs
What family is key in the control of apoptosis through dimerisation?
The Bcl2 family
What is one of the important branches of the Bcl2 family?
The pro-apoptotic BH123 protein (Bax, Bak, etc(?))
What can abnormal Bcl2 expression cause?
cancer, as it can be translocated onto antibody H chains thus leading to uncontrolled production and follicular lymphoma
What is the broad purpose of the inactivators of apoptosis (IAP)?
To add another layer of control to the process of apoptosis and inactivate apoptosis lol
What is the purpose of BH123 proteins?
When the intrinsic pathway is activated, they release anti-IAPs which block inactivators of apoptosis and thus allow the continuation of the pathway and apoptosis
What are the key mediators of caspases?
Cysteine in the active site (C)
Cleavage after aspartate (asp)
Protease (ase)
What do phenotypic changes in cells require?
Cleavage of cellular proteins by caspases
Give some examples of the action of caspases
Cleave ICAD -> destroy genetic information
Cleave PARP - prevent DNA repair
Cleave lamina -> break down nuclear architecture
cleave keratin -> break down cytoplasmic architecture
How does caspase activation occur?
An inactive procaspase is activated by cleavage mediated by an active caspase, thus producing an active caspase from the inactive procaspase
Why is apoptosis more complicated than it seems?
- Intrinsic and extrinsic pathways are linked
- Survival factors can override apoptosis
- Importance in carcinogenesis
- Calorie restriction lengthens lifespan – how
How do survival factors prevent apoptosis?
Through membrane receptors and generally the action of kinases or gene regulatory proteins
What can occur when apoptosis goes wrong?
- Autoimmune disease
- Cancer
- Neurodegeneration
How may a better understanding of apoptosis lead to treatments for disease?
• Can pathway components be drug targets?
– Bcl2 in lymphoma
– caspase 3 in Alzheimer Disease
– IAP in cancer
What is Pyroptosis?
A form of apoptosis
• Microbial trigger eg Salmonella
• Pattern recognition receptors
– NOD like and Toll like receptors
• Some features similar to both apoptosis and
necrosis
– Caspase 1 activation, not caspase 3
– Nuclear fragmentation but not cytoplasmic blebbing
– Pro-inflammatory
What is anoikis?
A form of apoptosis
- Death after losing contact with basement membrane/extra cellular matrix
- Apoptosis morphology
- How does metastasis occur?
