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 hydrolytic enzymes does S. auerus have and what do they cause?
Lipases, nucleases and hyalauronic acid - cause tissue destruction
How is chemotaxis inhibited by S. Aureus?
S. Aureus expresses CHIPS protein which binds to C5R and FPR (formlyated protein receptors) which means C5a and FP cannot bind, and therefore neutrophils cannot migrate up the gradient
what are the three methods of evading antibody opsonisation?
Hide antigens
Disrupt antibody functions
Prevent detection
How does staph Aureus hide its antigens?
S. Aureus has a capsule which helps to hide the antigenic structures that can be detected by the immune system
How does S. aureus prevent detected 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 molecule
How does S. aureus disrupt antibody function?
SpA binds to the IgG Fc region instead of their Fab region, which prevents normal opsonisation thus disrupting the normal function of the antibodies
What are the four key steps in the complement cascade?
- Initiation
- Formation of C3 convertase
- formation of C5 convertase
- MAC formation
What are the 4 ways in which S. aureus evades complement opsonisation?
- Inhibit the complement convertases
- Inhibit C3 processing
- Inhibit MAC formation
- Degrade complement components
What 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
Which S. aureus protein binds C3d in C3 to induce a conformational change?
Efb protein
when Efb protein binds C3d region of C3, what effect does this have?
induces a conformation change and prevents the binding of factor B to C3, so no C3bBb can be made
All three complement pathways result in what?
The formation of C3 convertase
What is a key step in the complement system?
The deposition of C3b on the surface of the microbe
What does the deposition of C3b on the microbe allow?
The detected 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?
SSL7 protein binds to C5 meaning no C5a is formed, meaning no C6-9, so no MAC
What is the name of a prtein which degrades antibodies by cleavage?
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 complement gradient
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 hydrogen peroxide which is produced by 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 FPR detect?
Formylated peptides
What do TLR receptors detect?
conserved microbial structures
What does CHIPS do?
protein which prevents C5a from binding to C5aR so no neutrophil migration
What does FLIPr and SSL5 do?
Inhibit phagocytosis as they inhibit Fc gamma and alpha
Does S. aureus secrete toxins which can kill neutrophils?
Yes
How could S. aureus evade immune responses by binding to neutrophil receptors?
Bind to neutrophil receptors which are involved in activating the neutrophil
Which strain of Staph expresses IdeS?
Streptococcus Agalactiae
What is the major cause of meningitis in neonates?
E. coli
What are the two C3 convertases and which pathways are each found in?
C3bBb (alternative) and C4bC2b (classical)
What does SpeB do?
degrades complement components - cleaves C3
What bacteria expresses SpeB?
S. pyogenes
What is the main toxin produced by S. aureus?
PVL
What toxin does B. pertusis produce?
Pertussis toxin
What does factor H do?
Inhibit C3 convertases
What is protein G and what expresses it?
It is an antibody binding protein like SpA that is expressed by S. dysgalactiae
