Anaerobic Life

Question 1

Zipper Mechanism

Answer 1

ex: Listeria, Yersinia, Campylobacter, Helicobacter

Question 2

Trigger Mechanism

Answer 2

Bacrerial type III/IV secretion system injects effectors into host cell –> actin/cytoskeletal components –> protrusions form endocytic vesicles

ex: Salmonella, Shigella, Chlamydia

Question 3

What type of agar does Legionella require?

Answer 3

BCYE (buffered charcoal yeast extract) + L-cysteine + Iron!

poorly gram staining, need silver stain to view

Question 4

What 2 clinical conditions are caused by Legionella?

Answer 4

1) atypical pneumonia (legionairres)

2) Pontiac Fever

Question 5

What is the reservoir for Legionella?

Answer 5

amoebae in fresh water

Question 6

Who is most at risk of falling ill from Legionella?

Answer 6

immunocompromised

Question 7

Pathogenesis of Legionella Pneumophila:

Answer 7

Inhaled –> OMPs/pili bind alveolar macrophage complment receptors –> MIP (macrophage infectivity potentiator) which is a surface protein, enhances phagocytosis –> “coiling phagocytosis” –> once inside, organism secretes effectors via DOT/LCM –> alters maturation of endosomal vacuole

Question 8

What is the overall mechanism of Legionella’s resistance of phagocytic clearance?

Answer 8

resists phagocyte killing by reprogramming phagosome maturation

Question 9

What is the overall mechanism of Listeria’s resistance to phagocytic clearance?

Answer 9

escapes phagolysosome

Question 10

MOA of how listeria resists phagocytic clearance?

Answer 10

entry into cell via zipper mechanism (Internalin A binds E-cadherin) –>phagosome fuses with lysosome –> decreased pH activates Listeriolysin O (LLO) and PLCs –> pore forming toxin which causes lysis of phagosome and bacteria replicates in cytosol –> once in cytosol ActA polymerizes actin and it pushes bacteria into adjacent cells.

Question 11

which bacteria can effectively avoid destruction by intracellular antimicrobial activity and extracellular immune strategies?

Answer 11

Listeria

Question 12

what is the overall mechanism of coxiella’s resistance to phagocytic clearance?

Answer 12

resists phagolysosomal killing mechanism

Question 13

MOA of coxiella’s resistance to phagocytic clearance?

Answer 13

phagocytosed by alveolar macrophages –> Lipid A acts as TLR4 ANTAGONIST –> phagosome fuses with lysosomes and recruits many other vacuoles and forms a giant Coxiella-containing vacuole (CCV) –> Coxiella is activated into replicative form by acidic pH –> Large Cel Variant (LCV) expresses several virulence factors that protect it form antimicorbial elements within vacuole

Question 14

what is the overall mechanism of mycobacterium TB’s resistance to phagocytic clearance?

Answer 14

RESISTANCE! can survive and grow within macrophages. waxy cell wall renders oranism impermeable and resistance to antimicrobial factors. doesn’t have normal virulence factors

Question 15

what is the MOA for mycobaterium’s resistance to phagocytic clearance?

Answer 15

phagocytosed by alveolar macrophages (complement receptors or mannose receptors) –> phagosomes inhibit phagosome-lysosome fusion (LIPOARABINOMANNAN AND CORD FACTOR (TREHAOLSE DIMYCOLATE)) –>

Question 16

what is cord factor?

Answer 16

protects mycobacterium TB from destruction. Serpentine stacks of cells.

Question 17

what is the immune response against mycobacterium TB?

Answer 17

TH1 triggers immune response with production of IFN-gamma. some pathogen will be killed but it is not enough. There is granuloma formation where epitheloid cells coalesce upon IFN-gamma and form multi-nucleated giant cells surrounded by activated T-lymphocytes (mainly CD4).

Question 18

what is the immune response to Legionella, Listeria, and Coxiella? (and other intracellular pathogens?)

Answer 18

produciton of IFN-gamma by Th1 cells which activated macrophages (and promotes CD8T cell effector functions). IFN-gamma activates macrophages by triggering enhanced receptor-mediated phagocytosis.

Question 19

what is the specific immune response for listeria?

Answer 19

cell-mediated response driven by Cytotoxic T lymphocytes (response similar to that against viruses).

CD4T lymphocytes become TH1 which activade CD8 which become cytotoxic and kill infected cells in MHC I dependent manner