pattern recognition receptors Flashcards
(36 cards)
what are PRRs?
innate immune cells that detect pathogens via pathogen associated molecular patterns (PAMPs)
diverse range of molecules - lipids, polysaccharides, nucleic acids
not species specific
damage associates molecular patterns (DAMPs)
host cell molecules or structures not normally visible to the immune system but can be released from damaged or dying cells
micro-organism associated molecular patterns (MAMPs)
molecules or structures that are specific for microbes and viruses not normally visible on host cells
overlaps with PAMPs but include structures on commensal microbes
how are commensal micro-organisms in the gut and lung tolerated by the immune system
a complex relationship exists but they are required for normal immune function
changes in the micro biome can have adverse effects on the immune system
what are PAMPs recognised by and where are the expressed
recognised by PRRs
expressed on all innate immune cells and in some cases T, B and endothelial cells
classes of PRRs
membrane receptors = toll like, c type lectin
cytoplasmic receptors = nod like, DNA and RNA
Lipopolysaccharide (LPS)
a component of gram -ve bacterial cell calls, structure vaires between bacterial strain species, very potent PAMP
what does loss of toll like receptor 4 protect mice from
endotoxic shock
how does sepsis occur
from systemic, bacterial or fungal infection
excessive production of pro-inflammatory cytokines
massive inflammation leads to organ failure and death
mortality driven by over activation of the immune system rather than invading the pathogen
injection of bacterial endotoxin can give rise to a similar condition where cytokine driven inflammation results in endotoxic shock and death
toll like receptor function
pathogen killing = phagocytosis, production of reactive O2 species
recruitment of immune cells to site of infection and activation of other immune cells = production of chemokines and proinflam cytokines
TLRs in infection
play important roles in activation host response to pathogens
IRAK4/Myd88 muts = increased susceptibility to bacterial infection
in childhood there is a 30-40% mortality rate even when treated with antibiotics
TLRs in cancer
TLR activation occurs during the killing of cancer cells by the immune cells, this process is subverted by cancer cells during tumour development
what does aberrant activation of TLRs contribute to
development of auto immune disorder - see notes to learn specific cases
Toll like receptors
part of the IL-1 receptor family, no of TLR genes is species dependent, diff TLRs in diff locations, diff TLRs recognise diff PAMPs
why is the correct localisation important for TLRs
must be in the position to bind to see the pathogen, must be in a location that minimises exposure to endogenous host ligands
what is the leucine rich repeat for in TLRs
for ligand binding
what does the activation of TIR domain allow
signalling
what is the toll/ interleukin 1 receptor homology domain for and where is it found
it mediates the interaction between TLRs and adaptor proteins - this is crucial to initiate down stream signalling
found in TLRs and IL-1 receptors present in TLR/IL-1 adaptor proteins
how do TLRs activate signalling
via Myd88 of Trif dependent signalling
all TLRs except TLR3 couple via
what is the name of the 2nd adaptor promotes TLR2 TLR4 and Myd88 recruitment
what do TLR3 and 4 couple via
Myd88
Mal
Tram
why is IRAK4 essential for myd88 dependent signalling
irak4 is essential - KO of irak4 in mice blocks responses to LPS and increases infection
- inactivating muts in humans results in invasive bacterial infection
how is IRAK recruited to myd88 for myd88 dependent signalling
via interactions between the death domain of myd88 and IRAK4
what does IRAK4 recruit and phosphorylate for myd88 dependent signalling and what does it activate
IRAK1 and 2 which activates the kinase of IRAK1
in myd88 dependent signalling what does IRAK2 lack
lacks catalytic residues in the kinase active site and is therefore inactive
