Bacterial Immune Evasion Flashcards
what is Staphylococcus aureus
Gram positive bacteria that is commensal and lives harmlessly in nose.
Is able to cause minor skin infections to severe and life threatening diseases.
what are the 2 groups S. Aureus can be divide into?
- localised pyogenic diseases characterised by tissue destruction, mediated by hydrolytic enzymes and cytotoxins
- diseases mediated by toxins that function as super antigens producing systemic diseases
What is a pyogenic disease?
one that causes pus to be produced
What are pyogenic diseases mediated by
hydrolytic enzymes and toxins
What are systemic diseases mediated by?
Toxins
what is S. Pyogenes
gram + bacteria , lives harmlessly in throat/
what 3 groups can S. Pyogenes be split into?
- localised diseases characterised by tissue destruction e.g pharyngitis
- diseases mediated by toxins that function as super antigens producing systemic diseases
- post- infection sequelae
How is chemotaxis inhibited by S. Aureus?
- S.Aureus releases CHIPs
- binds to C5aR
- prevents binding of C5a
- hence, neutrophils not activated as no C5a binding
what are the three main methods of evading antibody opsonisation?
- Use of capsules to hide bacteria
2.Use of surface proteins to prevent detection - Use of proteases to degrade antibodies
How is the expression of a capsule useful in bacterial immune evasion?
Use of a polysaccharide capsule helps to hide the antigenic structures of bacteria from adaptive immune components
How does S. aureus use surface proteins to prevent detection?
S. aureus has protein A on its surface (Spa).
Spa proteins bind to antibodies via their Fc (constant) region not their Fab (variable) region.
This prevents normal opsonisation, and therefore neutrophils cannot detect S. aureus.
How does S.pygones use surface proteins to prevent detection?
they have M surface proteins
these proteins bind to antibodies via their Fc (constant) region not their Fab (variable) region.
This prevents normal opsonisation, and therefore neutrophils cannot detect S.pyogenes
How can bacteria expressing proteases affect antibody opsonisation?
proteases cleave antibodies into many non-functional forms
This prevents IgGs binding to bacterial surface and performing their function.
what is another antibody opsonisation evasion strategy and why is it useful?
bacteria have antigenic variation.
Switching expression of antigens means antibodies that recognise the first surface structure are unable to recognise those bacteria now
what is complement opsonisation?
Complement system is composed of large number of proteins that react with one another to opsonise pathogens or to directly kill them by membrane attack complex (MAC) formation
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 bacteria specificallu S. Aureus evades complement opsonisation?
1.cleave complement factors such as C3
2. Inhibit C3/C5 convertases
3. recruit negative regulators
4. bind complement factors and prevent their processing
What protein binds to C3bBb and prevents the formation of C3 convertase and C5 convertase?
SCIN
How does S. aureus inhibit complement convertase?
Produces SCIN protein which binds to C3bBb and inhibits the formation of C3 convertase and C5 convertase
what are the 3 initiation pathways that result in C3 converts formation?
- classical pathway
- lectin pathway
- alternative pathway
What does the deposition of C3b on the microbe allow? d
The detected of the microbe by certain receptors on neutrophils / phagocytes
What is the name of a protein which degrades antibodies by cleavage?
IdeS - separates the Fc and Fab region
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? d
- 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 are pathogen recognition receptors? (PRRs)
directly detect microbes/microbial products. Cause neutrophils to become activated/primed.
what are the 3 main PRRs?
TLR receptors
CLEC receptors
FPR receptors
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?
inhibits chemotaxis of S. Aureus as prevents C5a from binding to C5aR which is a chemokine receptor
What does FLIPr and SSL5 do?
bind to Fc gamma receptors , preventing detection of IgG-opsonised bacteria => reduces antibody mediated phagocytosis
which bacteria releases FLIPr and SSL5 to block Fc receptors?
S. aureus
Does S. aureus secrete toxins which can kill neutrophils?
Yes
What is the major cause of meningitis in neonates?
E. coli
What does SpeB do?
its a protease that degrades C3 in S.pyogenes
which are the 2 proteases which degrade C3?
Aur
SpeB
which protease does S.Aureus release which degrades C3?
Aur
What bacteria expresses SpeB?
S. pyogenes
what are the 2 negative regulators that bacteria can recruit to evade complement opsonisation?
factor H
C4BP
What is the 3 toxins produced by S. aureus?
PVL
LUkAB
LukDE
what are the 2 toxins produced by S.Pyogenes that can kill neutrophils?
SLS
SLO
how do neutrophils sense and respond to their environment?
express hundreds of different immune receptors which allow them to sense their environment
how can immune receptors on neutrophils indirectly detect bacteria?
they can detect opsonised microbes through Fc receptors/complement receptors
how does S.Pygones inhibit chemotaxis?
It releases protein SpyCEP which cleaves CXCL8 + prevents binding to CXCR1/2 receptor
what does SpyCEP do
cleaves CXCL8 + prevents binding to CXCR1/2 receptor
which bacteria releases SpyCEP?
S.pyogenes
