Inflammation Flashcards
What do lectins do?
bind sugars on pathogen surfaces
What are toll like receptors?
they recognise different pathogens, TLR signalling switches on cytokine production, play a central role in activating macrophages and neutrophils
What does MHC I bind to?
CD8
What does MHC II bind to?
CD4
What is inflammation?
response to infection, damage/ trauma
What is inflammation characterised by?
calor (heat), dollar (pain), rubor (redness), tumour (swelling)
What is Acute inflammation?
local reaction. movement of proteins and cells from blood to tissue, predominantly neutrophils -> leads to resolution
What is Chronic inflammation?
prolonged inflammation, non- resolving, leads to loss of function, due to persistent inflammatory cells and mediators
What regulates an inflammatory response?
pro inflammatory eg’s: histamine, complement (c3a and c5a)
anti inflammatory: adrenaline and noradrenaline, cAMP
What are PRR’s and PAMPs?
- pattern recognition receptors
-pathogen associated molecular patterns
Where do PRRs bind to?
PAMPs
PRRs on the surface of phagocyte bind to PAMPS on the surface of pathogens
What does the binding of PRR and PAMP do?
-triggers the internalisation of the pathogen in the phagosome
-NADPH oxidase becomes activated and produces reactive oxygen species
-ROS are highly toxic to pathogens
What is oxidative burst?
rapid release of reactive oxygen species, mechanism of the innate immune response
What happens after oxidative burst?
inflammation
What do inflammatory cytokines and chemokine do?
-act on blood vessels, causes fluid and proteins to come out of the blood (exudate - fluid),
-inflammatory cells migrate into tissue- cause pain
What are TLRS?
toll like receptors - also part of pre family
What is a function of TLRs?
recognise wide range of PAMPs, sense infection
Explain dimerisation of TLR-1 and TLR-2 and its function:
TLR-1 and 2 are joined by a lipopeptide = dimerisation (heterodimer)
This causes cell activation
Why is TLR-4 dimerisation different?
TLR-4 can make a dimer with itself and is joined by LPS (homodimer)
Describe the steps in inflammatory cytokine production:
- TLR4- main receptor that detects LPS (PAMP)
-forms TLR4/MD2 complex, CD14 binds to LPS and presents it to TLR4/MD2 complex
-TLR4 recruits MyD88
-MyD88 recruits IRAK4 which becomes phosphorylated and activates other signalling molecules
-IRAK4 phosphorylates TRAF6
-TRAF6 activates IKK which frees NF-kB from its inhibitor (IkB)
-NF-kB enters nucleus and binds to promoter regions of specific genes that code for pro inflammatory cytokines -> triggers transcription
-MRNA is translated into proteins -> cytokines are secreted by macrophages - cytokines: increase vascular permeability, recruit additional immune cells = resolution
What does complement activation do?
1) recruits inflammatory cells
2) opsonises pathogens
3) kills pathogens
Where does C3b bind to ?
surface components of pathogen -> opsonisation
What is the function of C3a?
recruits phagocytes
What are the main classes of PRRs?
1) TLRs- found on cell surface and in endosomes of immune cells
2)Nod Like Receptors NLRs- found in cytoplasm of immune cells
3)CLRs - found on surface of dendritic cells
