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Infection And Immunity > How microbes avoid phagocytosis and killing > Flashcards

How microbes avoid phagocytosis and killing Flashcards

1
Q

what are the Microbe survival strategies

A

Strategy 1: Avoid being phagocytosed

Strategy 2: Subvert phagocytosis (escape from phagosome or avoid being killed)

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2
Q

how do microbes Avoid Phagocytosis?

A

– Inhibit phagocyte recruitment
– Kill phagocytes
– Resist phagocytosis

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3
Q

how do microbes Inhibit phagocyte recruitment?

A 
Directly inhibiting motility and chemotaxis
eg. Bordetella pertussis produces toxins
1. Adenylate cyclase 
» Increases cyclic AMP in neutrophils
» Leads to cell paralysis
2. Pertussis toxin
» Impairs migration of monocytes
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4
Q

how does Chlamydia inhibit phagocytes?

A

produce LPS with very low inflammatory activity to reduce phagocyte chemotaxis/activation

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5
Q

how do microbes kill phagocytes?

A

– release Leukocidins (exotoxins) kill neutrophils and macrophages
e.g. highly invasive bacteria Pseudomonas, staphylococci,

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6
Q

how does Streptococcus pyogenes kill leukocytes

A
  • by secreting leukocidins
  • Subunits oligomerize within the leukocyte membrane
  • Pore formation kills leukocytes
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7
Q

how do bacteria use the capsule in Resisting phagocytosis?

A

• Loose unstructured network of polymers on bacterial surface
• Polysaccharide mainly
• Antiphagocytic
• Decreased cell lysis by complement components
• Less complement C3b and C5b formation
• Some capsules mimic host polysaccharides
LPS is believed to be resistant to complement, acting in a similar manner to a capsule

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8
Q

how does Opsonisation can overcome the advantages of capsule?

A

appearance of antibodies allows clearance of Streptococcus pneumoniae

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9
Q

give an example of how Microbes avoid opsonization by antibodies?

A

Staphylococci
– Express bacterial surface protein, protein A (protein G)
– Binds to IgG molecules by the wrong end (Fc region)
– Cannot act as opsonins because Fc region not free to bind to Fc receptors on phagocytic cells

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10
Q

what is Avoidance of complement opsonisation?

A
  1. Non-opsonic phagocytosis
    Direct recognition and uptake by phagocytes
  2. Opsonic phagocytosis
    Phagocytosis of particles labeled with antibodies/complement
    • Complement (C3b)
    • Collectins (SP-A, SP-D)
    • Antibodies
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11
Q

what does Deposition of C3b cause?

A
  • Inflammation
  • Phagocytosis
  • Bacterial killing
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12
Q

why are Human cells not opsonized

A

Factor H prevents opsonization of sialic acid-containing surfaces

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13
Q

how does Neisseria avoid complement opsonisation?

A
  • modifies its LPS with sialic acid
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14
Q

how does M protein of Streptococcus pyogenes help the organism to resist phagocytosis?

A

–Binds H factor in serum (prevents complement opsonisation)

–Also binds fibrinogen (prevents phagocytosis)

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15
Q

how do Yersinia YOPs (Yersinia Outer Proteins) block complement?

A
  • block host cell actin polymersiation, preventing uptake of bacteria
  • YOPs are secreted into the host cells (Type III secretion)
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16
Q

how does Subversion of Phagocytosis occur?

A
  1. Escape into the cytoplasm
  2. Survival inside phagocytes
    - Inhibition of lysosome and phagosome fusion
    - Resistance to lysosomal contents
    - Inhibition of phagocyte oxidative pathway
17
Q

give an example of a bacteria that can Escape into the cytoplasm

A

Rickettsia (Rocky Mountain Spotted Fever) crosses membrane of phagosome to enter cytoplasm
– Since lysosomes do not secrete contents into cytoplasm, organism is safe
– Possess surface-bound phospholipase, which may weaken membrane

18
Q

Why block phagosome maturation?

A

• Limit hydrolytic capacity (ie addition of enzymes)
• Restrictinterfacebetweenpathogenandantigen processing/presentation
• Provide time for bacterial maturation/differentiation
Examples:
– Mycobacterium tuberculosis

19
Q

what is Mycobacterium tuberculosis?

A

Causes 2 million deaths each year

One third of world population is infected

20
Q

how is Mycobacterial phagosome maturation arrested

A
  • Lacks H-ATPase pump
  • Fails to fully acidify
  • Retain TACO (coronin)
  • Lacks many proteins found in normal phagolysosome
21
Q

what is TACO?

A

Newly formed phagosome is coated with a protein called “TACO” (tryptophan-aspartate-containing coat protein), also called “Coronin”

22
Q

how does TACO prevent maturation?

A
  • must be removed before phagosome can fuse with a lysosome.
  • Mycobacteria prevent TACO coat being removed, thus fusion is blocked
  • Macrophages with TACO gene knocked out rapidly kill mycobacteria by phagosome-lysosome fusion
23
Q

how does TACO modulate the vacuole?

A
  • Mycobacteria cause TACO to be retained, so the phagosome can’t fuse with the lysosome
  • Incontrast, M.bovis vacuole fuses with lysosome in TACO -ve macrophages
24
Q

what is Mycobacterial Mannosylated Lipoarabinomannan (ManLam)?

A
  • Component of the bacterial cell wall
  • Also used by M.tuberculosis to block phagosome / lysosome fusion
  • ManLam interferes with acquisition of lysosome, inhibits signalling pathway
25
Q

how are microbes Resistant to lysosomal contents?

A
  • microbes produce high-affinity binding proteins, siderophores that allow them to acquire iron sequestered by the host protein lactoferrin
    • Some microbes are resistant to cationic peptides
26
Q

what are Innate human ‘peptide antibiotics?

A

Cationic antimicrobial peptides = CAMPs

27
Q

name two CAMPs

A
  1. a-Defensin hNP-1 (Granulocytes, Macrophages, Paneth cells, T cells)
  2. -Defensin hBD1 (Epithelia, skin)
28
Q

give evidence that Host defence factors are ‘positive by nature’ - Bacteria are ‘negative by nature’

A 
1. Antimicrobial host factors are Positively charged
 • Antimicrobial peptides 
•Lysozyme
2. Bacterial cell envelope components are Negatively charged:
• Peptidoglycan
• Teichoicacids
• Phospholipids
• Lipid A, LPS,...
29
Q

give 2 negatively charged bacterial cell envelope

A

Gram-positive bacteria (Staphylococcus aureus)

Gram-negative bacteria (Shigella flexneri)

30
Q

how is Staph. aureus resistant to defensins

A
  • introduction of positive charges into the cell wall

- incorporation of D-ala into techie acids

31
Q

what are the Bacterial CAMP resistance mechanisms?

A
  1. Cleavage of CAMP PgtE protease: Salmonella, Escherichia
  2. Anti-CAMP Staphylokinase: Staphylococcus
  3. Extrusion of CAMP MtrCDE efflux pump: Neisseria
  4. Repulsion of CAMP
    - Modification of teich. acids and lipids:
    Staphylococcus, Listeria, Streptococcus, …
    - Modification of lipid A:Salmonella, Pseudomonas
32
Q

example of Survival inside phagocytes

A

Resistance to lysosomal enzymes—survive in phagolysosome (pH as low as 4)
Leishmania spp. (protozoa)—resistance may be due to:
– Resistant cell surfaces
– Secretion of enzyme inhibitors

33
Q

how does Inhibition of phagocyte’s oxidative pathway protect microbe?

A 
Legionella pneumophila (Legionnaire’s disease) Inhibits oxygen consumption in neutrophils
Reduces respiratory burst for killing microbes
34
Q

how do microbes become Resistance to Reactive oxygen and nitrogen intermediates

A
  • ROI detoxifiers, ROI scavengers
    Staphylococci—produce catalase, which degrades hydrogen peroxide
    • RNI : ROI detoxifiers interfere with RNI
35
Q

what are the Antibody effects?

A
  • Rickettsia coated with antibody can’t pass through membrane into cytoplasm
    • Antibodies don’t always prevent entry into cells, but can inhibit subsequent effects
    • Antibodies against Legionella prevent inhibition of phagolysosomal fusion
36
Q

name the Bacterial strategies to avoid being phagocytosed

A
  1. Capsule- Haemophilus influenzar
  2. Slime- Pseudomonas aeruginosa
  3. IgG improperly bound- Staphylococcus aureus
  4. Inhibition of chemotaxis- Bordetella pertussis
  5. Escape from phagosome- Shigella flexneri
37
Q

name the Bacterial strategies to avoid killing by phagocytes

A
  1. Alter phagosome maturation / lysosome fusion- Mycobacterium tuberculosis
  2. Resistance to oxidative killing- Mycobacterium tuberculosis
  3. Resistance to non-oxidative killing- Escherichia coli
  4. Failure of respiratory burst- Mycobacterium tuberculosis
  5. Inhibits macrophage activation- Mycobacterium leprae
  6. Kills macrophages- Yersinia enterocolitica
  7. Inhibition of antigen presentation- Mycobacterium tuberculosis

Infection And Immunity (16 decks)

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