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A10HA > 13 - Apoptosis > Flashcards

13 - Apoptosis Flashcards

1
Q

Molecular classification of 2018

A
  • intrinsic apoptosis
  • extrinsic apoptosis
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2
Q

What is apoptosis

A

terminates immune response after infection, eliminates self-
reactive lymphocytes or those without functional receptors, induced by cytotoxic cells

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3
Q

Apoptosis vs necrosis

A
  • apoptosis: regulated and controlled
  • necrosis: cell/tissue damage, causes inflammatory response
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4
Q

Purpose of apoptosis

A
  • Kills virally infected/malignant cells
  • Wound healing
  • Controls lifespan of immune cells
    (i) natural longevity
    (ii) reducing post-infection cell numbers
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5
Q

Apoptosis pathways

A

Differ in upstream events, converge on caspase activity

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6
Q

Caspases

A

Proteolytic enzymes (cysteine proteases) which cleave aspartic acid residues in target protein

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7
Q

Cells of apoptosis

A
  • Single cells or small clusters of cells
  • Cell shrinkage, pyknosis (chromatin condensation),karyorrhexis (nuclear fragmentation)
  • Intact cell membrane, cytoplasm retained in apoptotic bodies, no inflammation
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8
Q

Apoptosis pathways

A

Extrinsic pathway OR intrinsic pathway THEN execution pathway

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9
Q

Extrinsic pathway

A
  • receptor mediated
  • recruitment of adaptor proteins
  • activation of caspase 8
  • activation of caspase 3
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10
Q

Intrinsic pathway

A
  • stimulus e.g., absence of certain cell factors, presence of toxins
  • Changs in membrane permeability
  • release of pre-apoptotic proteins
  • activation of caspase 9
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11
Q

Execution pathway

A
  • cell shrinkage, chromatin begins to condense, membrane blebs form
  • extensive blabbing, chromatin heavily condensed, nucleus breaking down
  • formation of apoptotic bodies
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12
Q

Instrinic pathway in detail

A
  1. stimulus: e.g. absence of certain cell factors, presence of toxins
  2. pro-apoptotic proteins
  3. inhibit anti-apoptotic proteins e.g., Bcl-2
  4. [AIF, endocrine G, CAD –> nucleus (END)] OR [Smac/Diablo, Omi/HtrA2-inhibit IAPs (end)] OR [cytochrome c (cont.)]
  5. assembly of procaspase 9 with hepameric complex of Apaf-1 molecule
  6. caspase 9 activation
  7. activation of caspase 3
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13
Q

Extrinsic pathway in detail

A
  1. initiated by death receptors: members of TNF-receptor superfamily
    - Receptors contain ‘death domains’ (DD) in intra-cellular region
  2. recruitment of adaptor protein complex
    - proteins also contain death domains, e.g., FADD or TRADD
  3. death inducing signalling complex (DISC) forms
  4. activated caspase 8
    - complex associates with procaspase 8
  5. caspase 9 activation
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14
Q

Apoptosis and disease : cell attrition caused by excessive apoptosis

A

NEUROGENERATIVE DISEASE:
- huntingtons disease
- SMA
INFECTION
- sepsis
- shigellosis
- AIDS
ISCHEMIA
- stroke
- myocardial infarction
HEMATOLOGICAL DISEASE:
- MDS
- cyclin neutropenia
AUTOIMMUNE DISEASE
- type I diabetes
- hashimotos thyroiditis
METABOLIC DISEASE
- Wilsons disease
-alcoholic hepatitis

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15
Q

Apoptosis and disease : cell accumulation caused by defective apoptosis

A

MALIGNANT DISEASE:
- carcinoma
- leukaemia
- lymphoma
AUTOIMMUNE DISEASE:
- SLE
- ALPS
-rheumatoid arthritis
HEMATOLOGICAL DISEASE:
- polycythemia vera
- FHL

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16
Q

Features of necrosis

A
  • Triggered by interference with energy supply of cell
  • Direct membrane damage
  • Cell swells, cytoplasmic vacuoles form
  • Distortion/disruption of organelles such as ER, mitochondria, lysosomes
  • Detachment/disaggregation of ribosomes
  • Rupture of cell membrane, releasing cytoplasmic content
17
Q

Importance of apoptosis

A
  • Apoptosis important in many biological processes besides immunity.
  • Shows distinct cellular changes, ultimately seen as membrane bound, apoptotic vesicles, in which cell contents are safely contained.
18
Q

What is apoptosis dependent on?

A

Apoptosis is caspase dependent, with different caspases being activated depending on whether apoptosis is extrinsic or intrinsic

19
Q

What mediates extrinsic apoptosis?

A

Extrinsic apoptosis is receptor-mediated and involves caspase 8 and the formation of a death-induced signalling complex

20
Q

What can intrinsic apoptosis result from?

A

Intrinsic can result from absence of certain cell signals, or presence of toxins, and is mediated by caspase 9 and formation of the apoptosome

21
Q

What does caspase 3 trigger

A

Caspase 3 triggers the execution pathway from both the extrinsic and intrinsic pathways

A10HA (18 decks)

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