19 Fighting Macrophage

Question 1

what do TLR recognise

Answer 1

flagellin, bacterial DNA, peptidoglycan, LPS of outer membrane directly and the bound bacterium is engulfed into the macrophage

Question 2

what happens once bacterium engulfed

Answer 2

Once engulfed the bacterium is in a vesicle or phagosome (live bacteria if marked by antibodies or TLRs)

Question 3

what do endosomes do

Answer 3

bring more antibacterial factors to the phagosome until it becomes a phagolysosome and lyses the bacteria

Question 4

examples of bacteria that can divide in macrophages

Answer 4

Coxiella actively live and grow and divide inside macrophages, some more (Salmonella) survive and escape

Question 5

what happens if bacteria can resist the antibacterial activities

Answer 5

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

Question 6

can bacteria be carried around body

Answer 6

Being carried round the body as macrophages travel round the body - infect more – but need to deal with the lysozyme

Question 7

how do bacteria resist lysozyme

Answer 7

Modified bacterial cell wall to resist lysozyme

Question 8

what do special proteins bind to

Answer 8

Special proteins like haemoglobins to bind reactive N and O (ONOO-) radicals

Question 9

how do bacteria prevent macrophage from interacting with the phagosome membrane

Answer 9

Inhibit the V-ATPase of the macrophage from interacting with the phagosome membrane to acidify the interior

Question 10

what neutralises O- and H2O2

Answer 10

Catalase peroxidase enzymes to react with and neutralise O- and H2O2

Question 11

how do bacteria resist proteases

Answer 11

Extra surface layers or surface changes to resist protease

Question 12

what resists antimicrobial proteins

Answer 12

Changes in outer membrane to resist defensins which are antimicrobial peptides

Question 13

effect of bacteria resisting killing inside the macrophage

Answer 13

Interfere with signalling that macrophages use to induce phagosome maturation with endosomes and therefore their antibacterial activities

Question 14

examples of different bacterial pathogens can inhibit different processes in the maturation of the phagolysosome in macrophages so bacteria can live

Answer 14

Strep pyogenes

Neisseria

Question 15

Strep pyogenes growth

Answer 15

prevent normal fusion of the lysosome with the phagosome containing the Strep. Bacteria by making protein M1 on the phagosome

Question 16

Neisseria growth

Answer 16

make a protease that chews up the LAMP proteins which normally also allow endosome docking with antibacterial cargoes

Question 17

what is Klebsiella pneumoniae like

Answer 17

Gram negative pathogen

Question 18

where is Kp

Answer 18

asymptomatic reservoir in the gut but can circulate in the blood, the lungs, and causes lethal lung infections

Question 19

where are Kp in body

Answer 19

monocytes in bone marrow and blood and osteoclasts in bone may bind and engulf systemic Klebsiella pneumoniae bacteria

Question 20

what is Kp approach to resistance like

Answer 20

multipronged approach to resisting immune- killing- its capsule is important

Question 21

what treatment is there for Kp

Answer 21

lethal antibiotic resistant pathogen of humans

Question 22

what protects the Kp from immune system - AMPs

Answer 22

capsule can protect it against neutrophils and antimicrobial peptides (AMPs)

Question 23

how does Kp make a capsule

Answer 23

make a capsule using several operons of cps genes to make the carbohydrates and transport them

Question 24

what does the capsule resist

Answer 24

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

Question 25

what is changed for Kp OM

Answer 25

change their outer membrane composition , especially the lipidA part of the LPS when inside macrophages

Question 26

where are changes made in LPS and effect

Answer 26

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

Question 27

what prevents Kp merging with phagolysosome

Answer 27

survive inside special vacuoles KCVs

Question 28

what do Kp regulate

Answer 28

a key lysosomal regulator of the macrophage

Question 29

why does Kp not have a capsule inside KCV

Answer 29

may not help the later stage macrophage resistance once engulfed