Class #3 - Inflammation (part 1) Flashcards

1
Q

Apoptosis characteristics?

A

1-requires active RNA/p+ synthesis
2-Cell quickly replaced
3-No inflammation

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2
Q

Necrosis characteristics?

A
  • Cell and organelles swell
  • Membrane blebs
    last longer than apoptosis
  • Followed by inflammation
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3
Q

Apoptosis normal event eg.

A
Webbed digits in embryo
skin
intestines
cell infected by certain viruses
lens of eyes
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4
Q

Apoptosis initiation (2)?

A

1-Mitochondria: loss growth factor, DNA damage, misfolded p+

2-Death receptors on cell surface

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5
Q

Cell survival ?

A

receptors on surface when activated by (survival signal like growth factors) trigger the prod. of anti-apoptosis p+

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6
Q

Apoptosis execution in two pathways?

A

1- Intrinsic - mitochondria

2- Extrinsic - Death receptors

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7
Q

Intrinsic pathway?

A

Lack growth factors/DNA damage/misfolded proteins -> Bcl-2 family sensors activation -> activation of effectors Bax and Bak -> These dimerize and create passage in mitochondria which allows for leakage of cytochrome C + cofactors -> Initiator caspases -> Executioner caspases -> Breakdown of cytoskeleton/endonucleases activation -> cytoplasmic blebs -> apoptotic body with ligands for phagocytic cell receptors -> Phagocytosis

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8
Q

Anti-apoptotic p+

And mechanism of action

A

regulators of the Bcl-2 family : Bcl-2 and Bcl-XL.

- Antagonize Bax and Bak

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9
Q

Extrinsic Pathway Fas

A

Fas ligand (for Fas) ->Activation of death molecules on cell surface (mainly part of Tumor Necrosis Factor receptor family with a death domain inside the cell) Fas with a death domain -> Fas trimerize -> Creating the FADD (Fas Activating Death Domain) with 3 death domain inside the membrane -> Activation of caspase cascade -> Executioner caspases -> Breakdown of cytoskeleton/endonucleases activation -> cytoplasmic blebs -> apoptotic body with ligands for phagocytic cell receptors -> Phagocytosis

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10
Q

Extrinsic Pathway TNF

A

TNF binds to TNF receptor 1 (TNFRI) -> Creating the TRADD -> FADD -> Activation of caspase cascade -> Executioner caspases -> Breakdown of cytoskeleton/endonucleases activation -> cytoplasmic blebs -> apoptotic body with ligands for phagocytic cell receptors -> Phagocytosis

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11
Q

P+ misfolded apoptosis?

A

ER stress b/c p+ folding demand higher than folding capacity -> ER either adapt by decreasing p+ synthesis and increasing chaperone synthesis or triggers apoptosis.

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12
Q

Cell injury leading to apoptosis?

A

1-Accumulated misfolded p+ due to (mutation, cell stress, infections)
2- Radiation (dna damage)
3- Inflammation can lead to apoptosis

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13
Q

Cell injury leading to necrosis?

A

1-Hypoxia
2-Multiple injurious stimuli (ROS, damage lipids, p+ and DNA)
3- Inflammation

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14
Q

What is delayed prolonged inflammatory reaction?

A

Eg sunburn

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15
Q

Stimuli that can trigger acute infla?

A
INfection
Trauma
Tissue necrosis
foreign bodies
Immune reaction (=hypersensitivity reactions)
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16
Q

Acute inflam. steps?

A

1- Recognition of microbe, necrotic cells and foreign substances
2-Vascular changes: INcreased blood flow due to vasodilatation + increase vascular permeability
3-Leukocyte Recruitment
4- Leukocyte Activation

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17
Q

1- Recognition of microbe, necrotic cells and foreign substances?

A

1- Toll-like receptors (TLRs): Located in plasma membranes on endosomes and inside cytosol, allowing for extra/intracellular microbe identifications.
2- Inflammasomes: Located in cytosol and recognize extracellular ATP, product of cell death, uric acid, crystals and other microbial products.

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18
Q

Cause of redness and warmth in inflammation?

A

Arteriolar vasodilation -> increase blood flow and engorgement of down stream capillary beds

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19
Q

2-Vascular changes

A

Goal: Bring cells and p+ to site of injury/infection

  1. 1-Change in vascular caliber and flow
  2. 2- Increase vascular permeability
  3. 3-Response of lymphatic vessels: Increased drainage
20
Q

2.1. Change in vascular caliber and flow

A

a) Arteriolar vasodilation: increase blood flow => engorgement of down stream capillary beds (more in than out)
b) Blood stasis -> accumulation of leukocytes along vascular endothelial walls (margination)

21
Q

*Shunt in cap. bed?

A

Pre-capillary sphincters allow blood to bypass the cap. bed and go strait from the arteriole to the venules.

22
Q

Transudate vs exsudate

A

Almost p+, few blood cells

high p+, and lots blood cells

23
Q

2.2- Increase vascular permeability end result

A

Exudate, increase oncotic pressure in extravascular spaces causing edema and presence of WBC

24
Q

2.2- Increase vascular permeability mechanisms?

A

a) Endothelial cell contraction after binding to histamine, bradykinins, leukotrienes, etc.

25
Q
  1. Leukocytes recruitment
A
    1. Margination and rolling
  1. 2 Adhesion
  2. 3 Transmigration
  3. 4 Chemotaxis
26
Q

3.1. Margination ?

A

a) WBC flow near wall due to laminar flow, when low flow they come in contact with capillary walls.
Margination = when WBC accumulate near periphery of vessels.

27
Q

3.1 Rolling?

A

a) Weak/transient interaction between leuko. and endothelial cells = mediated by SELECTINS (found on both)
b) Expressed on endothelial by stimulation of histamine and thrombin

28
Q

CAMs?

A

Cellular adhesion molecules, include:
Selectins
Integrins
Member of Ig superfamily

29
Q

3 types of CAMs (on endothelial cells)? + roles?

A

GlyCAM: Rolling
VCAM-1: Adhesion
ICAM-1: Firm adhesion, arrest, transmigration

30
Q

3.2 Adhesion?

A

Binding of INTEGRINS (on both WBC and endo. cells) causes firm adhesion

31
Q

“pavementing” =

A

adhesion

32
Q

3.3 Transmigration?

A

Neutro. go between cells, then secrete COLLAGENASES to breakdown the basement membrane.

33
Q

Diapedesis=

A

Transmigration, which is extravasation of leuko. out of vessel to site of injury

34
Q

3.4 Chemotaxis

A

Leuko. follow gradient of [].

Different chemokines attract different cells

35
Q

Cell able to phagocytose ?

A

Monocytes/macrophage

36
Q

Basophils role in inflam.?

A

Similar as mast cells, but in blood: release histamine

37
Q

Neutrophils role in inflam.?

A
  • release lysosomal enz.
  • NETs (Neutrophiles, extracellular trap)
  • Phagocytose bacteria and release cytokines
38
Q

Eosinophils role in inflam.?

A
  • Parasites
39
Q

Monocytes role in inflam.?

A

-Induce systemic signs of infections :fever, etc
Become a and b when in tissues:
a)macro: phagocytos
b)dendritic: initiate adaptive immune response

40
Q

Lymphocytes role in inflam.?

A

T/B cells

41
Q

Macrophage activation?

A

Cytokines released by: Tcells, NK cells

TLRs recognition of antigens

42
Q

Types of macrophages (3)?

A

Anti-microbial
Wound healing
Regulatory macro.

43
Q

Cytokines released by macro?

A

IL, chemokinins, growth factors, interferons

44
Q

Inflammation sequence of events with cells?

A

Edema -> Neutrophils (peak 24h) -> Macro, bigger fight (there for days,weeks,months, etc)

45
Q

Phagocytosis stages

A
  1. Recognition and attachment
  2. Engulfment
  3. Killing and Digestion
46
Q

Phagocytosis stages 1. Recognition and attachment?

A

Receptors for complement or Fc portion of IgG

47
Q

Phagocytosis stages 2. Engulfment?

A

Membrane zip up around microbe. This becomes a phagosome inside the cytosol. Lysosome (with ROS and Enz.) fuse to the phagosome, becoming a phagolysosome