19 Fighting Macrophage Flashcards
what do TLR recognise
flagellin, bacterial DNA, peptidoglycan, LPS of outer membrane directly and the bound bacterium is engulfed into the macrophage
what happens once bacterium engulfed
Once engulfed the bacterium is in a vesicle or phagosome (live bacteria if marked by antibodies or TLRs)
what do endosomes do
bring more antibacterial factors to the phagosome until it becomes a phagolysosome and lyses the bacteria
examples of bacteria that can divide in macrophages
Coxiella actively live and grow and divide inside macrophages, some more (Salmonella) survive and escape
what happens if bacteria can resist the antibacterial activities
macrophage can be a stable home full of food and a way to be carried around the body
(as the macrophage travels) and to infect more cells
can bacteria be carried around body
Being carried round the body as macrophages travel round the body - infect more – but need to deal with the lysozyme
how do bacteria resist lysozyme
Modified bacterial cell wall to resist lysozyme
what do special proteins bind to
Special proteins like haemoglobins to bind reactive N and O (ONOO-) radicals
how do bacteria prevent macrophage from interacting with the phagosome membrane
Inhibit the V-ATPase of the macrophage from interacting with the phagosome membrane to acidify the interior
what neutralises O- and H2O2
Catalase peroxidase enzymes to react with and neutralise O- and H2O2
how do bacteria resist proteases
Extra surface layers or surface changes to resist protease
what resists antimicrobial proteins
Changes in outer membrane to resist defensins which are antimicrobial peptides
effect of bacteria resisting killing inside the macrophage
Interfere with signalling that macrophages use to induce phagosome maturation with endosomes and therefore their antibacterial activities
examples of different bacterial pathogens can inhibit different processes in the maturation of the phagolysosome in macrophages so bacteria can live
Strep pyogenes
Neisseria
Strep pyogenes growth
prevent normal fusion of the lysosome with the phagosome containing the Strep. Bacteria by making protein M1 on the phagosome
Neisseria growth
make a protease that chews up the LAMP proteins which normally also allow endosome docking with antibacterial cargoes
what is Klebsiella pneumoniae like
Gram negative pathogen
where is Kp
asymptomatic reservoir in the gut but can circulate in the blood, the lungs, and causes lethal lung infections
where are Kp in body
monocytes in bone marrow and blood and osteoclasts in bone may bind and engulf systemic Klebsiella pneumoniae bacteria
what is Kp approach to resistance like
multipronged approach to resisting immune- killing- its capsule is important
what treatment is there for Kp
lethal antibiotic resistant pathogen of humans
what protects the Kp from immune system - AMPs
capsule can protect it against neutrophils and antimicrobial peptides (AMPs)
how does Kp make a capsule
make a capsule using several operons of cps genes to make the carbohydrates and transport them
what does the capsule resist
capsule does resist opsonisation and so engulfment by macrophages as well as neutrophils but making different capsule types allows Kp to miss recognition by previous IgG antibodies
what is changed for Kp OM
change their outer membrane composition , especially the lipidA part of the LPS when inside macrophages
where are changes made in LPS and effect
changes are made in vivo inside a human (or mouse) host. The changes allow the K. pneumoniae to resist host antimicrobial peptides/defensins and not have their outer membranes damaged by them
what prevents Kp merging with phagolysosome
survive inside special vacuoles KCVs
what do Kp regulate
a key lysosomal regulator of the macrophage
why does Kp not have a capsule inside KCV
may not help the later stage macrophage resistance once engulfed
