What to attack? Flashcards
How does the IS distinguish pathogens from commensials, self-antigens and environmental antigens?
PRRs which recognise danger associated molecular patterns and pathogen associated molecular patterns (DAMPs and PAMPs). DAMPs are produced in the host in response to infection/tissue damage, alerting the IS.
How are PRRs encoded and what are they similar to?
They are individually encoded by specific genes and show low polymorphism. They are termed lectin-like; lectin is a protein which binds carbohydrates. They bind multivalently to exposed microbial surface sugars.
What is the molecular structure of PAMPs?
They can be polysaccharides or polynucleotides and differ minimally from one pathogen to another. Not synthesised by the host
Are PAMPS recognised by BCR or TCR?
No.
Name a class or PRRs
The Toll-like receptors (TLRs)
What does PRR engagement cause?
a signal which alerts the cells to the presence of infection and initiates cellular activation. A signalling cascade leads to the translocation of transcription factors; NFkB and IRF (interferon response factor), to the nucleus and causes the synthesis of pro-inflammatory cytokines.
What does TLR4 bind to?
LPS and viral dsRNA.
What does TLR5 bind to?
flagellin
What does TLR9 bind to?
unmethylated CpG DNA
Where can TLRs be found?
On the cell surface or endosomal compartments.
Can PRRS be secreted/ cell=-associated?
Yes; when secreted it is a direct pathogen attack with a proteolytic cascade leading to the lysis of pathogen. When cell-associated it cause the phagocytosis of a PAMP and associated microorganism, immune cell activation and release of inflammatory mediators.
Which cells release DAMPs?
Necrotic cells; initiates an immune response. Apoptotic cells do not. Necrosis and apoptosis are differentially induced due to the degree of injury inflicted onto that cells. - In apoptosis immune system is quiescent as DAMPs remain intracellular - regulated cell death, however the damaged cells is recognised by macrophages and phagocytosis of the apoptotic cell occurs
What does PAMP-mediated system stimulation result in?
The release of cytokines and chemokines (chemotactic cytokines which mediate the migration of phagocytes to site of PAMP release.
What do cytokines stimulate?
The endothelium causing cell contraction; facilitating cell migration and increase cytokine production (positive feedback), macrophges become activated and dendritic cells become differentiated.
What is the cascade of PAMP binding to PRR?
Binding causes MyD88 (thethered to PRR) to induce a signalling cascade which results in an IKK complex (IkB kinase) which then phosphorylates IkB (bound to NF-kB). Phosphorylated IkB is marked for degradations and NF-kB is now free to enter the nucleus to mediate the gene transcription of inflammatory cytokines such as interferons, interleukin-1, TNF and chemokines.
