Inflammation (L19) Flashcards
what is the purpose of inflammation?
restrict
• damage limitation
• stop pathogen movement
remove
• destroy invading pathogens
• clear damaged tissue
repair
• tissue regeneration
• healing/scarring
signs of inflammation
- erythema (redness)
- swelling
- heat
- pain
all leads to a loss of function
what are the 2 inflammatory responses?
innate immune response
adaptive immune response
innate immune response
rapid response at injury site
destruction of pathogens and phagocytosis
no memory component
adaptive immune response
specific response that can be remembered
triggered by innate activation
involves APCs, T cells and B cells
local inflammatory response
macrophages express receptors for many microbial constituents
bacteria trigger macrophages (through LPS) receptors to release cytokines and chemokine
vasodilation and increased vascular permeability causes redness, heat and swelling
inflammatory cells migrate to tissue, releasing inflammatory mediators that cause pain
stages of the innate inflammatory response
signalling is always there
inflammatory cell accumulation starts just after the microvascular event (6 hours)
you then get the systemic effects - makes you feel tired, pain and headaches
takes about 4 days before you see any healing
what cells are involved in local inflammation?
mast cells
macrophages
what do mast cells do?
important for clearing inflammation
communication hubs of the immune response
release granules containing histamine and active agents
what do macrophages do?
phagocytosis and activation of bactericidal mechanisms
antigen presentation
what does a tissue injury lead to the release of?
vasoactive mediators
chemotactic factors
what do vasoactive mediators cause?
- dilation of arterioles
- construction of venules
- increased vascular permeability
this leads to oedema
what do chemotactic factors cause?
the recruitment/stimulation of inflammatory cells
this leads to either chronic or acute inflammation
how do we resolve a tissue injury?
body wants to pull the 2 healthy edges together
• by clotting and fibrin
we don’t want fibrin there long term - has no activity
once wound is closed we want to replace fibrin with healthy tissue - complete restoration = no scarring
if fibrin is replaced with collagen there is scarring
what are eicosanoids?
structures that are 20 carbons in size
what is arachidonic acid?
an eicosanoid
the precursor for most inflammatory molecules
made from phospholipids by phospholipase A2 (a platelet activating factor)
what are the 3 classes of inflammatory molecules?
prostaglandins
thromboxanes
leukotrienes
they are all eicosanoids
prostaglandins
cycle-oxygenase converts arachidonic acid into PGH2 (an intermediate plastglastin)
PGH2 then gets converted into 2 compounds by cyclic endoperoxidases
what are the 2 compounds produced from PGH2 by cyclic endoperoxidases?
PGI2 (prostacyclin) - vasodilator, hyperalgesic, stops platelet aggregation
TXA2 (thromboxane) - thrombotic, vasoconstrictor, looks more like a box
leukotrienes
chemical mediators produced by white blood cells containing 3 conjugated double bonds between carbon atoms
they all come from arachidonic acid
12-lipoxygenase makes most of the compounds
5-lipoxygenase is the better target for drug action as it is further upstream so makes more products
what action could a drug perform to reduce inflammation?
- interfere with immune cell response
- block the pain signals (analgesic)
- prevent blood vessels becoming leaky
- stop cell infiltration to damaged tissue
- reduce body temp (antipyretic)
- prevent response from happening at all (immunosuppression)
what are anti-inflammatory drugs?
drugs used to combat pain and inflammation
what are the 4 categories of anti-inflammatory drugs?
antihistamines - antagonists of the histamine receptors
NSAIDS - non-steroidal anti-inflammatory drugs
glucocorticoids - steroidal anti-inflammatory drugs
immunosuppressants - reduction of immune cell activation or response
examples of NSAIDs
paracetamol
ibuprofen
aspirin
celecoxib
