Cell Death Flashcards

1
Q

What are the two types of subleathal injury to cells

A

Hydropic Change (oncosis) - accumulation of water. Steatosis - accumulation of fat

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2
Q

What is sublethal injury?

A

When a cell looses the ability to maintain homeostasis

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3
Q

What dangerous molecules are formed in the mitochondria?

A

Oxygen free radicles

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4
Q

Define necrosis

A

It is the death of tissue following the bioenergetic failure and loss of plasma membrane integrity

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5
Q

What does necrosis induce and what are the different types?

A

It induces an inflammatory response. The different types are;

  • Coagulative (necrosis in tissue),
  • Colliquative (necrosis in the brain),
  • Caseous (necrosis seen in tuberculosis),
  • Gangrenous (necrosis with rotting tissue),
  • Fibrinoid (necrosis in a microscopic feature of arterioles),
  • Fat necrosis (may follow trauma)
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6
Q

Describe Apoptosis?

A

Where individual cells are killed in a control manner and does not trigger inflammation. The cell is broken down into smaller membrane bound fragments which are then destroyed.

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7
Q

What is important about apoptosis involving DNA fragmentation

A

This can be interfered with using drugs in treatment of disease for example, inhibitors of PARP (molecule that tries to repair DNA when it is fragmented) are used in cancer.

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8
Q

How can macrophages recognise cells that need to be phagocytosed?

A

They recognise phosphatidylserine which appear on the outer leaflet of a cell when the membrane flips. This is an ‘eat me’ signal

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9
Q

What are the extrinsic and intrinsic factors that cause apoptosis

A

Extrinsic - receptors and T cells.

Intrinsic - Stress, metabolic, DNA damage and p53.

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10
Q

What are the key features of the extrinsic pathway using receptors

A

So you have receptor interaction from molecules such as (TNF family, Fas CD95 and inflammation) which trigger cytoplasmic singals activating the caspase cascade.

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11
Q

Describe the T cell Mediated extrinsic pathway

A

T cell hits target cell (viral cells or transplant cells) and interacts with the receptors. It then injects perforin and granzymes which activate the caspase enzymes.

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12
Q

Describe how the intrinsic pathway works

A

Endogenous activation of caspase enzymes which often involves mitochondrial damage as the mitochondria release products (Cytochrome C) which activate caspases.

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13
Q

What are apoptosomes and what are their functions

A

It is a large protein formed from the active components of apoptosis which overcome the suppressor of apoptosis

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14
Q

What is the role of p53

A

When radiation breaks the strand of DNA, this break is recognised by p53. It acts as a transcription factor causing new genes to be expressed. It can cause cell cycle arrest, DNA repair or cell death, therefore is prevents cancers.

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15
Q

What is the role of the Bcl2 family?

A

They are a family of proteins that either promote or inhibit apoptosis. They can exist as either homodimerisation or heterodimerisation.

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16
Q

Name an example of a Bcl2 that kills the cell

A

Bax-bax homodimerisation

17
Q

Abnormal Bcl2 expression can do what?

A

Contribute to formation of cancer. This is because genes on the chromosome undergo a translocation and rearrangement mutation.

18
Q

Name another layer of control in apoptosis and why this is important

A

IAP - which are inhibitors of apoptosis. Important because it blocks caspases so in cancers a drug could a be used against IAPs, promoting cell death

19
Q

What are Caspases?

A

a family of protease enzymes playing essential roles in programmed cell death and inflammation

20
Q

Name some targets of caspases

A
  • Cleave ICAD which destroys genetic info.
  • Cleave PARP which prevents DNA repair.
  • Cleave lamin which breaks down nuclear architecture.
  • Cleave keratin whch breaks down cytoplasmic architecture
21
Q

What are some survival factors and why are these important

A

Important - can block apoptosis. Examples are;

  • Increased production on anti-apoptotic Bcl2 protein.
  • Inactivation of pro-apoptotic BH3-only Bcl2 protein.
  • Inactivation of anti-IAPs
22
Q

What can arise from apoptosis gone wrong?

A

Autoimmune disease, cancers and neurodegeneration.

23
Q

What pathway compounents can be targeted by drugs?

A

Bcl2 in lymphoma, Caspase 3 in Alzheimer disease and IAP in cancers

24
Q

What is pyroptosis?

A

Cell death triggered by salmonella and has features similar to both apoptosis and necrosis. (caspase 1 activation, not caspase 3. Pro-inflammatory and nuclear fragmentation but not cytoplasmic blebbing)

25
Q

What is anoikis?

A

Death after losing contact with basement membrane/ECM