HTHSCI 1DT3 Lecture Notes - Lecture 19: Interleukin 13, Invagination, Hmgb1
23 Jun 2018
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Innate immunity and TLRs
Relies on recognition of PAMPS
These include:
1. Collectins e.g. mannose-binding lectin, surfactant proteins A & D
2. Complement
3. TLRs
4. NODs
5. Scavenger receptors
Danger Signal Hypothesis
The immune system requires the recognition of foreign antigen AND a danger signal from
injured tissues, as is more concerned with damage that ‘foreignness’
Hence Danger Associated Molecular Patterns (DAMPs) are key e.g. high mobility protein B1
At the immune synapse, where MHC binds TCRs, accessory molecule interactions like CD40-
CD40L will only occur if a DAMP is present.
If no DAMP is present, accessory molecule interactions will not occur, and further, the presence
of molecules like ILT3 may cause anergy or a suppressive immunomodulatory response
Collectins
Generally found on mucosal surfaces, except MBL – which circulates
Important for mucus clearance
Have a carboxy terminal c-type lectin domain, which undergoes Ca2+-dependant binding to
carbohydrates
Have an alpha-helical coiled coil
Collagen-like triple helix
N-terminal non-collagenous region
Surfactant Protein D is found in the stomach and SI’s mucous barrier, where it:
Binds, agglutinates ,inhibits and enhances phagocytosis of bacteria
It also enhances DC antigen uptake
Hence T cell responses are reduced in SP-D KO
Effective for small amounts of bacteria but can be overwhelmed
TLRs
Toll-like receptors (TLRs) have an extracellular region, which contains leucine-rich repeat motifs,
and a cytoplasmic tail, which has a Toll/interleukin-1(IL-1) receptor (TIR) domain
Activation triggers the activation of the innate immune system, as well as the development of
acquired immunity
TLR-signalling pathways originate from the TIR domain, as a result of its recruitment of TIR-
domain-containing adaptors — such as MyD88, TIRAP and TRIF
Signalling through each TLR requires MyD88 for the production of inflammatory cytokines.
However, a MyD88-independent pathway exists, and following signalling through TLR3 or TLR4,
it leads to the production of type I interferons through activation of TRIF and IRF3
TIRAP polymorphisms can lead to impaired TLR signalling and higher rates of bacteraemia, TB,
malaria and pneumococcal infection (even one polymprhism – heterozygosity – impairs)
The TLR-signalling pathways are negatively regulated by TLR-inducible molecules — such as
IRAK-M, SOCS1, MyD88s (MyD88 short), SIGIRR and ST2
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
These include: collectins e. g. mannose-binding lectin, surfactant proteins a & d, complement, tlrs, nods, scavenger receptors. The immune system requires the recognition of foreign antigen and a danger signal from injured tissues, as is more concerned with damage that foreignness". Hence danger associated molecular patterns (damps) are key e. g. high mobility protein b1. At the immune synapse, where mhc binds tcrs, accessory molecule interactions like cd40- Cd40l will only occur if a damp is present. If no damp is present, accessory molecule interactions will not occur, and further, the presence of molecules like ilt3 may cause anergy or a suppressive immunomodulatory response. Generally found on mucosal surfaces, except mbl which circulates. Have a carboxy terminal c-type lectin domain, which undergoes ca2+-dependant binding to carbohydrates. Surfactant protein d is found in the stomach and si"s mucous barrier, where it: Binds, agglutinates ,inhibits and enhances phagocytosis of bacteria. Hence t cell responses are reduced in sp-d ko.
