Inflammation Flashcards
What are the symptoms of acute inflammation?
- swelling and redness
- heat and fever
- pain
- loss of function
What are the major cell mediators of acute inflammation and what do they secrete?
- neutrophils - TNF-α
- macrophages - IL-6
- mast cells - IL-1
- endothelial cells - acute phase proteins
Describe prostaglandins and inflammation
- PGE2 can sensitise nerves to pain
- PGE2, PGE1 and others involved in vasodilation
- PGE2 involved in fever with IL-1
- production of PG is mechanism of action for NSAIDS
Describe PAMP/PRR in acute inflammation recognition
- innate cell recognition of pathogens
- macrophages and neutrophils
- also mast cells - not just Th2/IgE response
- TLRs and other PRRs also important
Describe DAMPs in acute inflammation recognition
- innate cell recognition of damage
- host proteins
- nuclear and cytosolic proteins usually hidden
- therefore innate immune system should only see when necrosis has occured
Describe DAMPs
- damage associated molecular patterns
- chromatin-associated protein high-mobility group box 1: HMGB1 - TLR4
- head shock proteins TLR-4
- DNA - TLR9
Describe the released mediators in acute inflammation
- activation of neutrophils, macrophages and mast cells
- secondary responses by endothelial cells
- releases TNF-α, IL-1, IL-6, Histamine and Chemokines CCL2, CCL5, CXCL8
What causes redness and heat in acute inflammation?
- IL-1 and TNF-α
- leads to vasodilation and vascular permeability
- capillaries closer to surface
What causes swelling in acute inflammation?
- chemokines
- cellular infiltration at site of infection/damage
- upreg of adhesion molecules on endothelia (IL-1)
Describe the acute phase response
- pro-inflammatory cytokines (mainly IL-6) lead to upreg & downreg of proteins
- release of acute-phase proteins in liver
- opsonisation
Describe the release of acute-phase proteins from liver in acute phase response
- haptoglobin
- fibrinogen
Describe haptoglobin
- increased in horses, cattle, rabbits, sheep, humans
- binds haemoglobin
- prevents bacteria requiring iron from gaining it
Describe fibrinogen
- increased in horses, rabbits, humans
- potential damage to tissues
- cleavage of fibrinogen to generate fibrin threads
- clot can block pathogen
Describe opsonisation
- mannan-binding lectin
- c-reactive protein
- complement
Describe complement in opsonisation
- C3a - mast cell activation/degranulation
- C4a - mast cell activation
- C5a - chemotaxis, vasodilation, neutrophil & mast cell activation/degranulation
What causes pain in acute inflammation?
- damaged endothelial cells and platelets produce pain response mediators - seratonin
- plasma leaking from blood vessels contains bradykinin
- seratonin and bradykinin stimulate nerve endings
What are some diseases associated with inflammation?
- sepsis
- toxic shock syndrome
- cytokine storm
Describe sepsis
- range of bacteria causes
- macrophages and DCs activated by bacteria
- overproduction of IL-1 and TNF-α
- increased blood vessel permeability, decreased blood pressure
- local and systemic effects of cytokines IL-1, IL-6 and TNF-α induce clinical symptoms associated with septic shock
Describe toxic shock syndrome
- caused by bacterial protein toxins: enterotoxin type B or TSST-1 or Spe1 and SpeC
- known as superantigens:
- bind to MHC class II and TCRs
- activates 5% of T cells - normally 0.01%
- production of TNF-α and IL-1
Describe cytokine storm
- hypersecretion of cytokines - positive feedback loop
- TNF-α, IL-1, chemokines etc
- Ebola, SARS
Describe chronic inflammation
- not only innate cells
- T cells important
- can be Th1, Th2, Th17
- caused by pathogens and non-pathogens
Describe resolution of inflammation
- Tregs and Macrophages have a role
- short half-life of inflammatory mediators
- production of pro-inflammatory prostaglandin and chemokines stops
- stops neutrophils migrating to site
- existing apoptotic neutrophils phagocytosed by macrophages
- major change in cell types
Describe Tregs and resolution of inflammation
- CD4+ T Cells producing anti-inflammatory cytokines are critical
- secrete IL-10 and/or TGF-β
- leads to downregulation of: Th1 production, MHC class II expression, co-stimulatory molecules
Describe macrophages and resolution
- M1 converts to M2
- M1 Th1 associated - IL-12
- M2 Th2 associated - IL-10, TGF-β, protease inhibitors
- balance of M1/M2 important in helminth infections, cancers, arthritis
