Cell Death Flashcards

1
Q

What is necrosis?

A

Dearth of tissues following bioenergetic failure and loss of plasma membrane integrity

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2
Q

What does necrosis induce?

A

Inflammation and repair

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3
Q

What may cause necrosis?

A

Ischaemia, metabolic causes, trauma causes, amongst others

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4
Q

What kind of necrosis is seen in the brain?

A

colliquative necrosis - liquifaction

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5
Q

What necrosis occurs in most types of tissues?

A

Coagulative necrosis - firm pale area with outline in microscopy

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6
Q

What necrosis occurs in tuberculosis?

A

Caseous necrosis - pale yellow semi solid material

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7
Q

What is gangrene?

A

Necrosis with putrefaction - follows vascular occlusion or certain infections and is distinctively black

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8
Q

What necrosis occurs as a microscopic feature in arterioles in malignant hypertension?

A

Fibrinoid necrosis

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9
Q

What us fibrinoid necrosis?

A

Fibrinoid necrosis occurs as a microscopic feature in arterioles in malignant hypertension

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10
Q

What necrosis may follow trauma and cause a mass, or follow pancreatitis and be visible as multiple white spots?

A

Fat necrosis

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11
Q

What does fat necrosis occur after?

A

Trauma as a mass

Pancreatitis as multiple white spots

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12
Q

How may necrosis be identified microscopically?

A

Cell go splat

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13
Q

What are the different types of necrosis?

A
Coagulative
Colliquative
Caseous
Gangrenous
Fibrinoid
Fat necrosis
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14
Q

When may apoptosis occur?

A
  • 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
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15
Q

What is the difference between the action of necrosis and apoptosis on DNA?

A

Apoptosis usually involves DNA fragmentation

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16
Q

What general rule is used t differentiate apoptosis and necrosis, especially on microscopy of effected cells?

A

Necrosis go SPLAT

Apoptosis - think fragmentation

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17
Q

What does the clearance of apoptotic cells by macrophages first require?

A

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

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18
Q

What are the tow types of ways that apoptosis can be induced?

A

Extrinsic pathway

Intrinsic pathway

19
Q

What are some examples of the extrinsic causes of apoptosis?

A

Receptors

T cells

20
Q

What are some examples of the intrinsic causes of apoptosis?

A

– Stress
– Metabolic
– DNA damage and p53

21
Q

What are the key features of the extrinsic pathway of apoptosis due to receptor action?

A

Receptor interaction
Cytoplasmic signals
Caspase cascade

22
Q

What may cause the extrinsic pathway of apoptosis due to receptor action?

A

TNF family
Fas CD95
Inflammation

23
Q

What are the key features of the T cell mediated extrinsic pathway of apoptosis?

A

Perforin and granzymes Cytoplasmic activation

24
Q

What may cause the T cell mediated extrinsic pathway of apoptosis?

A

Viral infection

Transplantation rejection

25
Q

What are the key features of the intrinsic pathway of apoptosis?

A

Endogenous activation Mitochondrial involvement

Cytochrome C is key

26
Q

What is a notable key step in the intrinsic pathway of apoptosis?

A

Release of cytochrome c from mitochondria

27
Q

What is apoptosome?

A

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

28
Q

How may radiation cause apoptosis?

A

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

29
Q

What family is key in the control of apoptosis through dimerisation?

A

The Bcl2 family

30
Q

What is one of the important branches of the Bcl2 family?

A

The pro-apoptotic BH123 protein (Bax, Bak, etc(?))

31
Q

What can abnormal Bcl2 expression cause?

A

cancer, as it can be translocated onto antibody H chains thus leading to uncontrolled production and follicular lymphoma

32
Q

What is the broad purpose of the inactivators of apoptosis (IAP)?

A

To add another layer of control to the process of apoptosis and inactivate apoptosis lol

33
Q

What is the purpose of BH123 proteins?

A

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

34
Q

What are the key mediators of caspases?

A

Cysteine in the active site (C)
Cleavage after aspartate (asp)
Protease (ase)

35
Q

What do phenotypic changes in cells require?

A

Cleavage of cellular proteins by caspases

36
Q

Give some examples of the action of caspases

A

Cleave ICAD -> destroy genetic information

Cleave PARP - prevent DNA repair

Cleave lamina -> break down nuclear architecture

cleave keratin -> break down cytoplasmic architecture

37
Q

How does caspase activation occur?

A

An inactive procaspase is activated by cleavage mediated by an active caspase, thus producing an active caspase from the inactive procaspase

38
Q

Why is apoptosis more complicated than it seems?

A
  • Intrinsic and extrinsic pathways are linked
  • Survival factors can override apoptosis
  • Importance in carcinogenesis
  • Calorie restriction lengthens lifespan – how
39
Q

How do survival factors prevent apoptosis?

A

Through membrane receptors and generally the action of kinases or gene regulatory proteins

40
Q

What can occur when apoptosis goes wrong?

A
  • Autoimmune disease
  • Cancer
  • Neurodegeneration
41
Q

How may a better understanding of apoptosis lead to treatments for disease?

A

• Can pathway components be drug targets?
– Bcl2 in lymphoma
– caspase 3 in Alzheimer Disease
– IAP in cancer

42
Q

What is Pyroptosis?

A

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

43
Q

What is anoikis?

A

A form of apoptosis

  • Death after losing contact with basement membrane/extra cellular matrix
  • Apoptosis morphology
  • How does metastasis occur?