Class #3 - Inflammation (part 1) Flashcards
Apoptosis characteristics?
1-requires active RNA/p+ synthesis
2-Cell quickly replaced
3-No inflammation
Necrosis characteristics?
- Cell and organelles swell
- Membrane blebs
last longer than apoptosis - Followed by inflammation
Apoptosis normal event eg.
Webbed digits in embryo skin intestines cell infected by certain viruses lens of eyes
Apoptosis initiation (2)?
1-Mitochondria: loss growth factor, DNA damage, misfolded p+
2-Death receptors on cell surface
Cell survival ?
receptors on surface when activated by (survival signal like growth factors) trigger the prod. of anti-apoptosis p+
Apoptosis execution in two pathways?
1- Intrinsic - mitochondria
2- Extrinsic - Death receptors
Intrinsic pathway?
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
Anti-apoptotic p+
And mechanism of action
regulators of the Bcl-2 family : Bcl-2 and Bcl-XL.
- Antagonize Bax and Bak
Extrinsic Pathway Fas
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
Extrinsic Pathway TNF
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
P+ misfolded apoptosis?
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.
Cell injury leading to apoptosis?
1-Accumulated misfolded p+ due to (mutation, cell stress, infections)
2- Radiation (dna damage)
3- Inflammation can lead to apoptosis
Cell injury leading to necrosis?
1-Hypoxia
2-Multiple injurious stimuli (ROS, damage lipids, p+ and DNA)
3- Inflammation
What is delayed prolonged inflammatory reaction?
Eg sunburn
Stimuli that can trigger acute infla?
INfection Trauma Tissue necrosis foreign bodies Immune reaction (=hypersensitivity reactions)
Acute inflam. steps?
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
1- Recognition of microbe, necrotic cells and foreign substances?
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.
Cause of redness and warmth in inflammation?
Arteriolar vasodilation -> increase blood flow and engorgement of down stream capillary beds
2-Vascular changes
Goal: Bring cells and p+ to site of injury/infection
- 1-Change in vascular caliber and flow
- 2- Increase vascular permeability
- 3-Response of lymphatic vessels: Increased drainage
2.1. Change in vascular caliber and flow
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)
*Shunt in cap. bed?
Pre-capillary sphincters allow blood to bypass the cap. bed and go strait from the arteriole to the venules.
Transudate vs exsudate
Almost p+, few blood cells
high p+, and lots blood cells
2.2- Increase vascular permeability end result
Exudate, increase oncotic pressure in extravascular spaces causing edema and presence of WBC
2.2- Increase vascular permeability mechanisms?
a) Endothelial cell contraction after binding to histamine, bradykinins, leukotrienes, etc.
