Bacterial immune evasion

Question 1

What does antibody opsonisation allow? [2]

Answer 1

• Deposition of complement in the classical complement pathway
• Neutrophils and other phagocytes the ability to detect invading microbes

Question 2

State the 5 methods of action through which bacteria evade anitbody opsonisation.

Answer 2

1) Hide antigens
2) Disrupt functions
3) Prevent detection
4) Degrade antibodies
5) Modify antigenicity

Question 3

What is main function of capsule polysaccharide expression

Answer 3

Hides antigens from immune system components

Question 4

What are the effects of S.aureus expressing protein A which binds to Fc region of IgG?

Answer 4

Prevents detection
Prevents normal opsonisation and therefore neutrophils cannot detect S.aureus.

Question 5

What is the effect of S.pyogenes expressing M protein which binds to Fc region of IgG?

Answer 5

Prevents normal opsonisation and therefore neutrophils cannot detect S.pyogenes

Question 6

What is the effect of S.aureus expressing SSL10 which binds to Fc region of IgG?

Answer 6

Inhibit neutrophil detection of antibody

Question 7

What is the effect of IdeS from S.pyogenes protease cleaving enzymes?

Answer 7

IdeS cleaves or modifies antibodies in order to prevent normal opsonisation and therefore neutrophils cannot detect S.pyogenes.

Question 8

What is the effect of Opa and LOS antigens on N.gonorrhea to evade antibody opsonisation?

Answer 8

Modify antigenicity

Question 9

What is the effect of Cap on S.pneumoniae to evade antibody opsonisation?

Answer 9

Modify antigenicity

Question 10

What are the 4 general steps of the complement cascade?

Answer 10

1) Initiation
2) Formation of C3 convertase
3) Formation of C5 convertase
4) MAC formation

Question 11

What are the 5 mechanisms through which bacteria evade complement opsonisation?

Answer 11

• Cleave complement factors
• Inhibition of C3 or C5 convertases
• Acquire host derived complement regulators
• Bind complement factors and prevent their processing

Question 12

What is the effect of SCIN protein from S.aureus binding to C3bBb in evading complement opsonisation?

Answer 12

Inhibits formation of C3 or C5 convertase
Prevents:
1) C3b deposition
2) C3a formation
3) C5a formation

Question 13

What is the effect of S. pyogenes expressing SpeB proteases on evading complement opsonisation?

Answer 13

Degrade C3 which prevents
1) C3b deposition
2) C3a formation
3) C5a formation

Question 14

What is the effect of proteases on evading complement opsonisation? and how does S.aureus do this

Answer 14

S. aureus expressing Aur
Degrade C3 which prevents
1) C3b deposition
2) C3a formation
3) C5a formation

Question 15

What is the effect of proteases on evading complement opsonisation? and how does S.pyogenes do this

Answer 15

S.pyogenes expressing SpeB
Degrade C3 which prevents
1) C3b deposition
2) C3a formation
3) C5a formation

Question 16

What is the effect of acquiring host-derived complement regulators on evading complement opsonisation and how does S.aureus do this?

Answer 16

Recruits factor H onto their surface and expresses Sbi
- Inactivates C3b, which inhibits C3 convertases

Question 17

What is the effect of acquiring host-derived complement regulators on evading complement opsonisation and how does S.pyogenes do this?

Answer 17

Recruits C4BP and factor H to surface
Degrades C2a from C3 convertases

Question 18

What do neutrophils have on their surface to sense and response to their environment?

Answer 18

Immune receptors such as Pathogen recognition receptors (PRRs)

Question 19

What are the 3 types of PRR? What do they detect?

Answer 19

• TLR receptors- Toll-like receptors that detect conserved microbial structures
• CLEC receptors - C type lectin receptors detect microbial carbohydrates
• FPR receptors - Formylated peptide receptors which detect formylated peptides

Question 20

How can neutrophils indirectly detect bacteria?

Answer 20

• Fc receptors on neutrophils detect antibody opsonised microbes
• Complement receptors on neutrophils detect complement opsonised microbes

Question 21

What are ITAMs?

Answer 21

Activating motifs in cytoplasmic tails of Fc receptors

Question 22

What are the 4 different classes of immune receptors that modulate function?

Answer 22

• Activatory receptors - enhance immune cell activity
• Inhibitory receptors - suppress immune cell activity
• Cytokine receptors - detect cytokines and signal neutrophils
• Chemoattractant receptors - for chemotaxis

Question 23

State the ways bacteria dysregulate neurtrophil function

Answer 23

• Inhibit chemotaxis
• Inhibit detection of bacteria
• Kill neutrophils
• Disrupt intracellular signalling

Question 24

How can bacteria inhibit chemotaxis to evade neutrophil detection and how does S.aureus do this?

Answer 24

ChIPs binds C5aR and prevents binding of C5a
- Neutrophils do not migrate to sites of infection
- Neutrophils do not become activated through C5aR

Question 25

How can bacteria inhibit chemotaxis to evade neutrophil detection and how does S.pyogenes do this?

Answer 25

SpyCEP cleaves CXCL8 and prevents binding to CXCR1/2
- Neutrophils do not migrate to sites of infection
- Neutrophils do not become activated through CXCR1/2

Question 26

How can bacteria prevent phagocytosis to evade neutrophill detection/killing? and how does S.aureus do this?

Answer 26

• FLIPr binds Fcy receptors preventing the detection of IgG opsonised bacteria
• SSL5 binds Fc a receptors preventing the detection of IgG opsonised bacteria
  These mechanisms reduces antibody mediated phagocytosis and killing of S.aureus

Question 27

What 3 toxins does S.aureus produce that kill neutrophils?

Answer 27

PVL toxin
LukAB
LukDE

Question 28

What 2 toxins does S.pyogenes produce that kill neutrophils

Answer 28

• SLS
• SLO

Question 29

What is the effect of bacteria killing neutrophils?

Answer 29

• Fewer neutrophils at the site of infection that can kill bacrteria
• This reduces phagocytosis of S.aureus and S.pyogenes

Question 30

How does each bacteria inhibit the effects of microbials?

Answer 30

Release proteins that inhibit effects of these antimicrobials
S.aureus (SPIN)
S.pneumoniae (SP_1749)
Y.pestis (YopE)
P.aeruginosa (ExoS)

Question 31

How does each bacteria modify bacterial surface?

Answer 31

Switch expression of certain surface proteins
- N.meningitidis (Opa)
- E.coli (O and K antigens)
- S.pneumoniae (Cap)