4.7 Bacterial Immune Evasion Flashcards
What is a pyogenic disease?
One that causes pus to be produced
What are pyogenic diseases mediated by?
Hydrolytic enzymes and cytotoxins
What are systemic diseases mediated by?
Toxins
What are 5 methods of evading antibody opsonisation?
Hide antigens
Disrupt antibody function
Prevent detection of opsonised bacteria
Degrade antibodies with proteases
Modify antigenicity (switching antigen expression)
What are 5 ways in which bacteria can dysregulate neutrophil function?
Inhibit chemotaxis
Inhibit detection of bacteria
Kill neutrophils
Stimulate inhibitory receptors
Disrupt intracellular signalling
What hydrolytic enzymes does S. auerus have and what do they cause?
Lipases, nucleases and hyaluronic acid
Cause tissue destruction
How does S. aureus hide its antigens?
S. aureus has a polysaccharide capsule which helps to hide the antigenic structures that can be detected by the immune system
How is chemotaxis inhibited by S. aureus?
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
How does S. aureus prevent detection by antibodies?
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
How does S. aureus disrupt antibody function?
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
What is the complement system?
Large number of proteins that react with one another to opsonise pathogens or kill them by membrane attack complex formation
What are the four key steps in the complement cascade?
- Initiation
- Formation of C3 convertase
- Formation of C5 convertase
- Membrane attack complex formation
What are the 4 ways in which S. aureus evades complement opsonisation?
Inhibit complement convertases
Inhibit complement components (C3, MAC)
Degrade complement components with proteases
Recruit host-derived regulators
What S. aureus protein binds to C3bBb and prevents the formation of C3 convertase and C5 convertase?
SCIN
How does S. aureus inhibit complement convertase?
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
Which S. aureus protein binds C3d in C3 to induce a conformational change?
Efb protein
What effect does Efb protein binding have?
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
All three complement pathways result in what?
The formation of C3 convertase
What does the deposition of C3b on the microbe allow?
Detection of the microbe by certain receptors on neutrophils/phagocytes
Why are C3a and C5a so essential?
They are chemoattractants and therefore attract the components needed for MAC complexes - C6, C7, C8, C9
How is MAC formation inhibited by S. aureus?
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
What is the name of a protein which degrades antibodies by cleavage and how?
IdeS – separates the Fc and Fab region
How do C3a and C5a result in neutrophils arriving at the site?
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
What primes neutrophils?
The gradient of complement proteins
Why is S. aureus a common cause of food poisoning?
Because they are able to grow in high salt concentrations
What two enzymes does S. aureus have?
Coagulase and catalase
What does catalase do?
Protects the cell by degrading H2O2 produced by the neutrophil
What does coagulase do?
Converts fibrinogen into fibrin so that blood clots can form
What are three toxins that S. aureus has?
Enterotoxins
Exfoliative toxins
Toxic Shock syndrome toxin
What does the exfoliative toxins of S. aureus cause?
Cause the superficial layers of the skin to peel off
What does enterotoxin do?
Causes food poisoning as it is heat stable and acid resistant
Describe neutrophil action during an infection?
- Pathogen enters blood stream
- Pathogen opsonised by antibodies and complement
- This triggers the complement cascade
- Results in the formation of C3a and C5a which forms a gradient
- C3a binds to C3aR and C5 binds to C5a receptors, on endothelium
- This triggers the dnothelium to increases the expression of ICAM
- This causes neutrophils to be recruited to the site - they bind to the lining and migrate through
- Then activated and perform effector functions
What do neutrophil CLEC receptors detect?
Microbial carbohydrates
What do FPRs on neutrophils detect?
Formylated peptides
What do TLR receptors on neutrophils detect?
Conserved microbial structures
How are pattern recognition receptors involved in neutrophil priming and activation?
PRPs detect microbes or microbial products directly
How are antibodies and complement involved in neutrophil priming and activation?
Microbes are opsonised by antibodies and complement
Neutrophils detect these opsonised microbes with Fc or complement receptors
What do activatory and inhibitory receptors do?
Activatory – enhance immune cell activity
Inhibitory – suppress
What does FLIPr and SSL5 do?
Bind Fc gamma and alpha receptors
Prevents detection of IgG-opsonised bacteria, inhibiting phagocytosis
How does S. aureus kill neutrophils?
Secretes toxins
What are the two C3 convertases and which pathways are each found in?
C3bBb (alternative) and C4bC2b (classical)
What is the major cause of meningitis in neonates?
E. coli
What does SpeB do?
Degrades complement components - cleaves C3
What bacteria expresses SpeB?
S. pyogenes
What is the main toxin produced by S. aureus and what does it do?
PVL toxin, kills neutrophils
What toxin does B. pertusis produce?
Pertussis toxin
What does factor H do?
Inhibit C3 convertases
What is protein G and what expresses it?
Antibody binding protein like SpA that is expressed by S. dysgalactiae
How does S. aureus prevent phagocytosis?
Expresses FLIPR that binds to Fc-gamma receptors on neutrophils, preventing IgG detection
Expresses SSL5 that binds to Fc-a receptors, preventing IgA detection
How does S. aureus inhibit activating receptors?
Expresses surface molecules that bind and block activating receptors
How can N. meningitidis and E. coli evade detection by neutrophils?
Modifying bacterial surface proteins
N. meningitidis – switches Opa protein expression
E. coli – switches O and K antigen expression
