Antibacterial autophagy Flashcards
What does cell autonomous innate immunity refer to?
that all nucleated cells can protect themselves from pathogenic invasion
What are the options intracellularly for pathogens to live?
vesicles or cytosol
What do extracellluar pathogens face in terms of immunity?
antibodies; complement; phagocytes
What do vesicular pathogens face interms of immunity?
low pH; hydrolytic enzymes; radicals
What do cytosolic pathogens face in terms of immunity?
autophagy; inflammasome; host clel death
Give examples of pathogens that live in the cytosol?
shigella; listeria
What is autopahggy?
enclosure of cytoplasmic constituents in a double membrane vesicle- autophagosome
What proteins are required for autophagy?
ATG proteins
Which ATG proteins are particularly important for autophagy?
ATG8/LC3
What name is given to bacterial autophagy?
xenophagy
What fuses with autophagosome?
late endosomes or lysosomes
What are the 3 general stages in xenophagy?
intial danger signal; cargo labelling; label decoding
What protein is used for cargo labelling?
ubiquitin
What is used for label decoding?
autophagy adaptor/receptor
What is hte function of autophagy receptors?
decode “eat me” signals and drags intracellular microbes into autophagosomes
What are the 3 domains found on autophagy receptors?
one for interaction ot immune signalling; LIR domain and one which recognises an eat me signal
What is the LIR region for?
LC3 interacting region which ensures targeting of the autophagy receptor to LC3 anchored in the phagosome membrane
Give examples of autophagy receptors?
NDP52; optineurin; T6BP
What happens when NDP52 is missing?
rampant intracellular bacteria
Which types of cell is ubiquitin foudn in?
eukaryotic cells
By what type of bonding does ubiquitin modify other proteins?
covalently
How many enzymes does ubiquitin linkage require ?
3
How are ubiquitin chains formed?
by lysine residues- the shape of the chain determiens the repsonse to the ubiquitin
How does the cell recognise cytosolic bacteria?
bursting of the vacuole exposes host carbohydrates that aren’t normally present
Which receptor is responsible for detecting cytosol exposed carbohydrates?
danger receptor- galectin-8
What receptor is galectin-8 able to bind directly to?
NDP52
What is macro-autophagy?
delivers cytoplasmic cargo to the lysosome through the autophagosome
What is micro-autophagy?
cytosolic components are directly taken up by the lysosome through invagination of the lysosomal membrane
What is chaperone-mediated autophagy?
targeted proteins are translocated across the lysosomal membrane in a complex with chaperone proteins that are recognised by a receptor LAMP-2A
How does salmonella escape its salmonella containing vacuole?
type 3 secretion system
What is a good marker for autophagy?
LC3
