4.7 Bacterial Immune Evasion

Question 1

What is a pyogenic disease?

Answer 1

One that causes pus to be produced

Question 2

What are pyogenic diseases mediated by?

Answer 2

Hydrolytic enzymes and cytotoxins

Question 3

What are systemic diseases mediated by?

Answer 3

Toxins

Question 4

What are 5 methods of evading antibody opsonisation?

Answer 4

Hide antigens
Disrupt antibody function
Prevent detection of opsonised bacteria
Degrade antibodies with proteases
Modify antigenicity (switching antigen expression)

Question 5

What are 5 ways in which bacteria can dysregulate neutrophil function?

Answer 5

Inhibit chemotaxis
Inhibit detection of bacteria
Kill neutrophils
Stimulate inhibitory receptors
Disrupt intracellular signalling

Question 6

What hydrolytic enzymes does S. auerus have and what do they cause?

Answer 6

Lipases, nucleases and hyaluronic acid

Cause tissue destruction

Question 7

How does S. aureus hide its antigens?

Answer 7

S. aureus has a polysaccharide capsule which helps to hide the antigenic structures that can be detected by the immune system

Question 8

How is chemotaxis inhibited by S. aureus?

Answer 8

S. aureus expresses CHIPS protein which binds C5aR and FPR1

Thus C5a and formylated peptides cannot bind, and neutrophils do not migrate or become activated

Question 9

How does S. aureus prevent detection by antibodies?

Answer 9

Has SSL10 – a secreted protein which binds to the Fc region of IgG which prevents the Fc receptors on neutrophils from detecting IgG on the surface of the bacteria

Question 10

How does S. aureus disrupt antibody function?

Answer 10

Spa protein binds to the IgG Fc region instead of their Fab region, which prevents normal opsonisation thus disrupting the normal function of the antibodies

Question 11

What is the complement system?

Answer 11

Large number of proteins that react with one another to opsonise pathogens or kill them by membrane attack complex formation

Question 12

What are the four key steps in the complement cascade?

Answer 12

1. Initiation
2. Formation of C3 convertase
3. Formation of C5 convertase
4. Membrane attack complex formation

Question 13

What are the 4 ways in which S. aureus evades complement opsonisation?

Answer 13

Inhibit complement convertases
Inhibit complement components (C3, MAC)
Degrade complement components with proteases
Recruit host-derived regulators

Question 14

What S. aureus protein binds to C3bBb and prevents the formation of C3 convertase and C5 convertase?

Answer 14

SCIN

Question 15

How does S. aureus inhibit complement convertase?

Answer 15

SCIN protein binds C3bBb and inhibits the formation of C3 convertase and C5 convertase

This prevents:
Deposition of C3b – less detection
Formation of C3a – less neutrophil recruitment
Formation of C5a – less MAC formation

Question 16

Which S. aureus protein binds C3d in C3 to induce a conformational change?

Answer 16

Efb protein

Question 17

What effect does Efb protein binding have?

Answer 17

Binds C3d region of C3, inducing a conformational change

Prevents factor B binding C3, thus no C3bBb made
Prevents C3dg binding CR2 on phagocytes, thus less detection

Question 18

All three complement pathways result in what?

Answer 18

The formation of C3 convertase

Question 19

What does the deposition of C3b on the microbe allow?

Answer 19

Detection of the microbe by certain receptors on neutrophils/phagocytes

Question 20

Why are C3a and C5a so essential?

Answer 20

They are chemoattractants and therefore attract the components needed for MAC complexes - C6, C7, C8, C9

Question 21

How is MAC formation inhibited by S. aureus?

Answer 21

SSL7 binds C5 thus no C5a is formed

Since C5a is a chemoattractant, the components for MAC formation (C6-9) are not attracted, thus no MAC are formed

Question 22

What is the name of a protein which degrades antibodies by cleavage and how?

Answer 22

IdeS – separates the Fc and Fab region

Question 23

How do C3a and C5a result in neutrophils arriving at the site?

Answer 23

They bind to their respective receptors on the epithelial cells, which causes the epithelial cells to increase the expression of ICAM which results in neutrophils recruited to the area

Question 24

What primes neutrophils?

Answer 24

The gradient of complement proteins

Question 25

Why is S. aureus a common cause of food poisoning?

Answer 25

Because they are able to grow in high salt concentrations

Question 26

What two enzymes does S. aureus have?

Answer 26

Coagulase and catalase

Question 27

What does catalase do?

Answer 27

Protects the cell by degrading H2O2 produced by the neutrophil

Question 28

What does coagulase do?

Answer 28

Converts **fibrinogen into fibrin** so that blood clots can form

Question 29

What are three toxins that S. aureus has?

Answer 29

Enterotoxins Exfoliative toxins Toxic Shock syndrome toxin

Question 30

What does the exfoliative toxins of S. aureus cause?

Answer 30

Cause the superficial layers of the skin to peel off

Question 31

What does enterotoxin do?

Answer 31

Causes food poisoning as it is heat stable and acid resistant

Question 32

Describe neutrophil action during an infection?

Answer 32

1. Pathogen enters blood stream 2. Pathogen opsonised by antibodies and complement 3. This triggers the complement cascade 4. Results in the formation of C3a and C5a which forms a gradient 5. C3a binds to C3aR and C5 binds to C5a receptors, on endothelium 6. This triggers the dnothelium to increases the expression of ICAM 7. This causes neutrophils to be recruited to the site - they bind to the lining and migrate through 8. Then activated and perform effector functions

Question 33

What do neutrophil CLEC receptors detect?

Answer 33

Microbial carbohydrates

Question 34

What do FPRs on neutrophils detect?

Answer 34

Formylated peptides

Question 35

What do TLR receptors on neutrophils detect?

Answer 35

Conserved microbial structures

Question 36

How are pattern recognition receptors involved in neutrophil priming and activation?

Answer 36

PRPs detect microbes or microbial products directly

Question 37

How are antibodies and complement involved in neutrophil priming and activation?

Answer 37

Microbes are opsonised by antibodies and complement Neutrophils detect these opsonised microbes with Fc or complement receptors

Question 38

What do activatory and inhibitory receptors do?

Answer 38

Activatory – enhance immune cell activity Inhibitory – suppress

Question 39

What does FLIPr and SSL5 do?

Answer 39

Bind Fc gamma and alpha receptors Prevents detection of IgG-opsonised bacteria, **inhibiting phagocytosis**

Question 40

How does S. aureus kill neutrophils?

Answer 40

Secretes toxins

Question 41

What are the two C3 convertases and which pathways are each found in?

Answer 41

C3bBb (alternative) and C4bC2b (classical)

Question 42

What is the major cause of meningitis in neonates?

Answer 42

E. coli

Question 43

What does SpeB do?

Answer 43

Degrades complement components - cleaves C3

Question 44

What bacteria expresses SpeB?

Answer 44

S. pyogenes

Question 45

What is the main toxin produced by S. aureus and what does it do?

Answer 45

PVL toxin, kills neutrophils

Question 46

What toxin does B. pertusis produce?

Answer 46

Pertussis toxin

Question 47

What does factor H do?

Answer 47

Inhibit C3 convertases

Question 48

What is protein G and what expresses it?

Answer 48

Antibody binding protein like SpA that is expressed by **S. dysgalactiae**

Question 49

How does S. aureus prevent phagocytosis?

Answer 49

Expresses **FLIPR** that binds to **Fc-gamma** receptors on neutrophils, preventing **IgG detection** Expresses **SSL5** that binds to **Fc-a** receptors, preventing **IgA detection**

Question 50

How does S. aureus inhibit activating receptors?

Answer 50

Expresses surface molecules that bind and block activating receptors

Question 51

How can N. meningitidis and E. coli evade detection by neutrophils?

Answer 51

Modifying bacterial surface proteins N. meningitidis – switches Opa protein expression E. coli – switches O and K antigen expression