PHGY 459 Flashcards
What are the 3 phases of inflammation?
- Inflammatory phase (d0 – 3):
Key process: blood clotting, vasoconstriction, immune cell recruitment/infiltration (neutrophils, then M1 macrophages)
- Platelet activation & degranulation
- Chemotaxis of immune cells
- Negative regulation to prevent excessive inflammation
Purpose: prevent infection, remove debris, prepare the wound for healing
- Proliferative phase (d3 – 30)
Key process: Fibroblast activation, collagen deposition (III), angiogenesis, re-epithelialization
- Differentiation & migration of keratinocytes
- ECM synthesis by fibroblasts
- Local hypoxia induces autophagy promote cell survival
Purpose: rebuilt tissue and restore blood supply
- Remodeling phase (d10 – 1y or more)
Key process: collagen is reorganized from type III → I, increased tensile strength, reduction in scar size
- Contraction of scar?
- Decrease in cellularity and vascularity
- Apoptosis
- M2 macrophages
what is the definition of autophagy?
Lysosome-dependent, self-renewal mechanism that can degrade and recycle cellular components cellular organelles/protein are engulfed by double-membrane structure called autophagosome
- Autophagosome = double-membrane vesicle
- Promote cell survival → clearance ROS
- Fuse with lysosome for degradation + recycling
- Provides energy and building blocks
What are the main takeaways of this paper?
Keratinocyte-Macrophage Crosstalk by the Nrf2/Ccl2/EGF Signaling Axis Orchestrates Tissue Repair
- Epidermal nrf2 initiates a regenerative response through Ccl2 regulation
- Ccl2 release by basal stem/progenitor keratinocytes prompts macrophage trafficking (required for macrophage attraction)
- Ccl2 regulates EGF production in macrophages trafficked to the injury site
- Ccl2 treatment brought back healing - EGF from macrophages stimulates basal keratinocytes
What are the main takeaways of this paper?
Keratinocyte autophagy enables the activation of keratinocytes and fibroblasts and facilitates wound healing
Looked at → wound closure (histological slides), delayed re-epithelization + granulation tissue formation
Epidermal autophagy is critical for keratinocyte proliferation and differentiation onset during wound healing.
Epidermal autophagy facilitates the activation of fibroblasts and the recruitment of macrophages, neutrophils, and mast cells
- Autophagy → TNF-mediated CCL2 transcription
- Facilitates wound repair through regulating CCL2 expression recruitment of …
- Ccl2 was low in atg5 KO and atg7 KO
- Autophagy Ccl2 keratinocyte proliferation and migration
- Enhance fibroblast activation
Wounding induces expression of autophagy genes → TNF → NFkB-mediated expression of autophagy (positive feedback)
What is the MyD88 pathway?
Pathway1: MyD88-Dependent → Proinflammatory Cytokines
Key Features
- Activated by: TLR4 (at plasma membrane, activated by LPS), TLR2 (via Pam3CSK4)
- Adaptor protein: MyD88
- Signaling intermediates: TRAF6, TAK1, clAP1/2
- Modification of TRAF3: K48-linked ubiquitination, leading to degradation
Functional outcome:
- Activates MAPKs (p38, JNK) and IKK complex
Induces NF-xB and AP-1-driven expression of proinflammatory cytokines (.g., IL-6, TNF)
Mechanism
1. MyD88 recruits TRAF6 and TRAF3 to TLR4.
2. TRAF6 activates clAP1/2 via K63-linked ubiquitination.
3. clAP1/2 then mediate K48-linked degradative ubiquitination of TRAF3.
4. Degradation of TRAF3 allows the signaling complex (MyD88, TAK1, TRAF6) to translocate to the
cytosol, enabling MAPK activation.
5. Results in expression of inflammatory cytokines.
What is the TRIF pathway?
Pathway2: TRIF-Dependent → Type I Interferon Response
Key Features:
- Activated by: TLR3 (via poly I:C), or TLR4 after endocytosis
- Adaptor protein: TRIF
- Signaling intermediates: TRAF3, TBK1, IRF3
- Modification of TRAF3: K63-linked non-degradative self-ubiquitination
Functional outcome:
Activates IRF3 (via dimerization and nuclear translocation) Induces expression of type I interferons (IFN-a, IFN-B)
What is the difference between NAIP5 and NAIP2?
NLR → cytosolic receptors inflammasome complex → cleave active caspase-1
NAIP = NLR family apoptosis inhibitory protein → acts as both inhibitor of apoptosis + sensor of pathogens
- Mediates assembly of inflammasomes for inflammatory caspase activation
- NAIP5 binds to flagellin → NAIP5-NLRC4 inflammasome assembly
- NAIP2 binds to PrgJ → NAIP2-NLRC2 inflammasome assembly
What are the 4 layers of the colliculus in frogs?
- Contrast detectors → slowest fibers
- Unmyelinated
- No adaptation
- Directional sensitivity - Convexity detectors
- Unmyelinated
- Respond to edges/cures (more when more curved)
- Suppressed by uniform motion (motion of the background), prefers small jerky displacement instead of smooth movement → fly detector - Moving edge detectors
- Myelinated
- No preference for direction of motion - Dimming detector
- Myelinated
- Respond when light goes down, but not when light goes up
What cells are bug detectors of frogs?
Convexity detectors
What are the differents in MT?
- V2 thick stripes
- V1 layer 4b
- Superior Colliculus
*Magnocellular cells
What are 2 types of outputs of MT?
- Optic flow → MST, VIP
- Generation of eye movement → LIP FEE, SC
What are the 2 steps of face perception?
- Detection → as a whole, focus on common features
- Measurement & categorization → focus on differences
What does dynasore do?
What does SM do?
Prevent LPS-induced internalization of TLR4
Smac mimetics (SMs) induce the degradation of both cIAP1 and cIAP2, which are cellular inhibitors of apoptosis, through a process involving auto-ubiquitylation and proteasomal degradation
