Acute Inflammation Flashcards
What is acute inflammation characterized by?
Movement of serum proteins and leukocutes (esp granulocytes - neutrophils, eos, baso.) from the blood –> extravascular compartments
Describe the vascular and cellular phase of inflammation
- vascular phase: vessel dialation and increased permeability promotes the movement of plasma and proteins (e.g. fibrin, Abs)
- cellular phase: chemotactic mediators and endothelial cell activation recruit immune cells (esp granulocytes) through extravasation
What are the five signs of inflammation? Include latin term
- calor (heat)
- rubor (redness)
- tumor (swelling)
- dolor (pain)
- functio laesa (LOF)
For both acute and chronic inflammation:
- definition
- when does the response first appear
- how long does it last
- which cells are involved
acute:
- definition: limited tissue response that starts immediately after injury
- onset: immediate
- duration: several days - IT RESOLVES
- cells: 1st - innate immune cells (PMNs); 2nd - lymphocytes
chronic:
- definition: prolonged response
- onset: delayed onset
- duration: months to years
- cells: lymphocytes, MFs, and plasma cells (adaptive IS is the primary driver of acute inflammation)
What initiates inflammation?
PAMPS and DAMPS
Describe NF-kB activation
- IKK complex phosphorylates NF-kB:IkB
- NF-kB:IkB-P is ubiquitulated and IkB is degraded in the proteosome
- NF-kB translocates to the nucleus
What defines the TLR/IL-1 superfamily?
TIR domain
For the following PAMPs, what TLR do they activate, and where is that TLR located:
- LPS
- flagellin
- dsRNA
- ssRNA
- CpG DNA
- LPS –> TLR4 (pm)
- flagellin –> TLR5 (pm)
- dsRNA –> TLR3 (endosome memb)
- ssRNA –> TLR 7/8 (endosome memb)
- CpG DNA –> TLR 9 (endosome memb)
Describe the MyD88 and TRIF signaling pathways of activated TLRs
MyD88 –> TRAF 6 –> TAK 1 –> NF-kB –> proinflammatory cytokines
TRIF –> TRAF 6 –> etc
TRIF –> TRAF 3 –> IRF3 –> type 1 IFNs
What are NLRs? What are the two subfamilies, give examples for each subfamily
NLRs = intracellular sensors of PAMPs that enter the cell via phagocytosis or pores, and DAMPs associated with cell stress
Subfamilies
1. NLRC: NOD1/2, NLRC3/4/5
2. inflammasomes: NLRP3
Describe the formation of the inflammasome and its function
formation: PYD of NLRs binds to adapter protein ASC (PYCARD) via PYD-PYD interaction –> ASC links NLRs to inactive form of caspase 1 via the CARD domain
function: aggregation of pro-caspase 1 –> autocleavage to active caspase 1 –> caspase 1 cleaves pro-IL-1B to IL-B1 (inflammatory cytokine) + activates pore proteins –> cytokine release (creates the ILs and opens the door)
What are RLRs? Give a couple examples of RLRs and what they activate.
RLRs = family of cytoplasmic PRRs that sense RNA, provide frontline defense against viral infections in most tissues
e.g. RIG-I and MDA5 –> activate NF-kB
what are CLRs? give examples of DC and MF CLRs and their functions
CLRs = carbohydrate-binding lectins, require Ca2+ for binding
examples:
* CLECs
* MMR –> scavenger R
* DEC-205 –> cross presentation
* dectins –> fungi detection
* langerin –> specific of Langernans cells
What are KLRs?
NK cell lectin-like Rs: both activating and inhibitory types
DAMPs
For the following DAMPs, state their intracellular location and their receptors:
* genomic DNA
* HMGB1
* ATP
* uric acid crystal
- genomic DNA: nucleus, TLR9
- HMGB1: nucleus, TLR2/4, RAGE
- ATP: cytosol, P2Y2, P2X7
- uric acid crystals: cytosol, NLRP3