Recognition of infection Flashcards
what is CRP?
a marker for infection that is made by the liver
when does C3 bind to microbe membranes?
when the thioester domain in the alpha-domain of C3 is activated. The thioester domain is prevented from activation by the inhibitory beta-domain
how is the thioester domain in the alpha domain of C3 activated?
C3 removes the beta-chain that normally inhibits the thioester domain and exposes the highly reactive alpha-chain thioester domain
what is C3b and what is its function?
C3b is the active compliment molecule
- it immediately binds to adjacent microbes, or is inactivated by hydrolysis
what is the function of complement inhibitors?
prevent complement from binding and/or inactivate complement
what is caused by CD59 deficiency?
Paroxysmal nocturnal haemoglobinuria
- characterised by episodes of erythrocyte lysis
what is CD59?
a complement inhibitor expressed on host cells
what is the mechanism of CD59?
prevents final assembly of the membrane attack complex at the C8 to C9 stage
what are the features of Toll-like receptors?
recognize many types of pathogen molecules
-homologous to fruit fly toll receptor
- dimers with leucine-rich repeat (LRR) domains that bind PAMPs and DAMPs
how are gram positive and gram negative recognised differently by TLR?
gram-negative and gram-positive display different molecules for recognition by the innate immune system. While both types of membrane can be destroyed by lysozyme, we have different recognition systems for each class of bacteria
what detects gram-negative bacteria?
Gram-negative bacteria cell membranes contain lipopolysaccharide which is detected by TLR-4
what detects gram-positive bacteria?
Gram-positive bacteria have lipoteichoic acid (detected by TLR-2
what does TLR binding of PAMPs activate?
signalling pathways
what signalling pathways do PAMPs activate?
NF-kappaB transcription factor activation
Interferon regulating factor (IRF) pathways
MAP kinase pathway downstream transcription factors such as AP-1
what do TLRs recruit to their TIR domain?
different TLRs recruit different adapter proteins to their TIR domain
what are the interferon regulating factor pathways important for?
important for antivirus response/recognition
associated with interferon response (MHC-I and MHC-II upregulation response to viral infection)
what does the ligand binding the the TLR trigger?
adaptor recruitment to the TIR domain
transcription factor is activated and DNA binds
what can transciption factors do once they are activated?
they can cross the membrane
how do dendritic cells use toll like receptors?
utilise toll like receptors as a key bridge between the innate and adaptive immune response
what is the role of nucleic acid sensors?
induce a IFN type 1 response that protects other cells against virus infection
how do RIG-I and MDA5 act as nucleic acid sensors?
RIG-I and MDA5 detect short (uncapped) dsRNA and long dsRNA
- Activated RIG-I or MDA5 coalesce on mitochondria with MAVS to activate IRF and NF-kappaB transcription factors
- Interferon Type I (IFN-alpha and IFN-beta) transcription induced aling with other anti-viral genes
how does RIG-I work?
RIG-I-like helicase detects cytoplasmic RNAs
- RIG-I recognises uncapped RNA with 5’ trophosphate (no methyl guanosine (usual cap))
-RIG-I activation results in Type I interferon production, as well as classic NK kappaB induced genes
what is IL-6?
interleukin that acts on the liver to induce release of acute phase reactants
what stimulates the release of IL-6?
bacteria
what is an indicator of bacterial infection?
C reactive protein
what is C reactive protein (CRP)?
a protein that in synthesised in the liver and is the most important clinical marker for bacterial infection
what is the role of CRP?
binds phosphocholine of bacterial cell surfaces
when does rapid production of IL-6 occur?
during bacterial infection
- often when symptoms of illness are the worst
what is fibrinogen?
precursor to fibrin clots
- binding bacteria
