Lecture 25: Preformed Defences Flashcards
When are chemicals with anti-microbial properties found in body ?
In anticipation of infection
What is phagocytosis not just ?
An innate cellular process
What is the function of phagocytic receptors ?
Enhance phagocytic activity, add specificity and enhance inflammation
What are the downstream consequences of phagocytosis ?
Dynamic signalling/metabolic events that kill pathogen
What is the function of the respiratory burst ?
At the phagosomal membrane liberates toxic radicals
What are the steps involved in macrophage phagocytosis ?
- Contact with solid triggered/cargo
- Formation of phagocytic cup
- Internalisation and formation of the phagosome
- Intracellular fate ?
- Fusion with acidic lysosyme for degradation of cargo via catabolic enzymes, respiratory burst, acidic environment
- Recycling of cargo
- Escape of cargo
What is found inactive on neutrophil 2* granule or mac lysosyme membrane ?
NADPH oxidase, cytochrome B558 complex
What is the plasma membrane activated by in respiratory burst ?
GPCR- fMLP-Receptor
What does the GPCR fMLP recognise ?
Bacterial formyl-MET (PAMP) fMLP tri-peptide
What does GPCR signalling do ?
Exchanges GDP-GTP activating signalling - Rac2
What does Rac2 trigger ?
Relocalisation of cytoplasmic NADPH oxidase subunits p40, p47, p67
Where is the fully active NADPH oxidase ?
Mature lysosyme/granule
What does the fully active NADPH oxidase generate ?
Superoxide
What are the phagocytic receptors ?
- C-type lectin receptor
- Scavenger receptor
What does the lectin/sugar binding domain recognise ?
Bacterial and fungal cell wall components
What do c-type lectin receptors trigger ?
Internalisation (phagocytosis)
What part of the c-type lectin receptor interacts with kinases ?
Intracellular ITAM domain
What part of the c-type lectin receptor interacts with kinases ?
Intracellular ITAM domain
What is an example of C-type lectin receptors ?
Dectin-1 recognises fungal B-(1,3)-GLUCANS
What do scavenger receptors recognise ?
- Modified self
2.Pathogens
What does Dectin-1 signalling trigger ?
Intracellular signalling via hemi-ITAM, adapter syk
What is ITAM ?
Immunoreceptor tyrosine based activation motif
What is [YxxL]6-8aa[YxxL] ?
4 amino acid motif repeated but separated
Where are ITAMs present ?
Cytoplasmic tails of non-catalytic tyrosine-phosphorylated receptors
What does phosphoryltion create ?
Docking sites for other adapters with SH2 domains
Where are ITAMs found ?
CD3
What is hemi-ITAM ?
1 motif, brought together by dimerisation - syk activation
Where is Hemi-ITAM found on ?
CLRSs
What is ITIM ?
Inhibitory motif, recruits phosphatases not kinases
How does Dectin-1 respond ?
Triggered by different ligands, different types of Beta-glucans depending on how ligand/Beta-glucan is presented
What do the signalling receptors of transcriptional activation recognise ?
Danger, trigger intracellular signalling pathways and transmit the signal further to culminate in activation of various TRC factors
