Bacterial Immune Evasion Flashcards
What are common features of bacteria that our body can detect?
LPS in Gram-negative bacteria
LTA in Gram-positive bacteria
Flagella on certain bacteria
What are the three major stages that bacteria can evade?
Antibody opsonisation
Complement opsonisation
Neutrophil functions
What are our innate immune cells?
Neutrophils
Eosinophils
Basophils
Dendritic Cells
Macrophages
- the innate immune response is very efficient at detecting and killing invading microbes
What are facts about neutrophils?
Most abundant leukocyte (50-70%) in the blood
Recruited to areas of infection
Detect microbes
Perform effector functions-> kill microbes
Considered simple immune cells
What do neutrophils do?
Why must neutrophil responses be balanced?
Neutrophil responses must be balanced to prevent infection, but also, prevent damage (inflammation) to the host.
What is Staphylococcus aureus?
Gram-positive bacterium, that is a commensal and lives harmlessly in the nose of 30% of human population. S. aureus is an opportunistic pathogen able to cause minor skin infections to severe and life-threatening diseases.
- S.aureus has evolved many sophisticated mechanisms to evade neutrophils
What is Streptococcus pyogenes?
Gram-positive bacterium, that can live harmlessly in the throat of humans. S. pyogenes is an opportunistic pathogen able to cause a range of disease including cause pharyngitis (Strep throat), skin infections, scarlet fever and sepsis.
- S.pyogenes has evolved many sophisticated mechanisms to evade neutrophils
What is antibody opsonisation?
Antibodies bind bacterial antigens, allowing…
- the deposition of complement in the classical complement pathway
- neutrophils and other phagocytes the ability to detect invading microbes
How do bacteria evade antibody opsonisation?
Capsule polysaccharide hides the antigens
e.g., S.aureus and S.pyogenes
Surface proteins bind Fc region of antibodies
e.g., S.aureus (Protein A aka Spa) and S.pyogenes (M protein)
Proteases to degrade antibodies
e.g., S.pyogenes IdeS
Explain in more detail the capsule polysaccharide.
Bacteria can expresses capsule on their surface.
This helps to hide antigenic structures that can be detected by innate and adaptive immune components, such as complement and antibodies
Explain in more detail the surface proteins binding Fc region of antibodies.
Spa and M surface proteins bind antibodies via their Fc region not their Fab region.
This prevents normal opsonisation, and therefore neutrophils cannot detect S. aureus or S. pyogenes.
Explain in more detail proteases to degrade antibodies.
Proteases cleave or modify antibodies.
This prevents normal opsonisation, and therefore neutrophils cannot detect S. pyogenes.
Overall, what are the S.aureus and S.pyogenes antibody evasion methods?
Capsule expression
Inhibit antibody opsonisation- Spa and M protein
Degrade antibodies- ideS
What is special about the proteins involved in immune evasion?
They often perform the same function. they:
1) hide antigens
2) disrupt functions
3) prevent detection
4) degrade antibodies
5) modify antigenicity
This helps to ensure immune evasion is successful.
How do N.gonorrhoeae and S.pneumoniae evade?
antigenic variation
(altering surface antigens)
N.gonorrhoeae= OPA and LOS antigens
S.pneumoniae= Cap
Do bacteria only have one method of evading immunity?
No, many bacterial pathogens utilise multiple strategies to evade antibody opsonisation.
What is the complement opsonisation?
Complement system is composed of a 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 key steps of the complement cascade?
1) initiation
2) formation of C3 convertase
3) formation of C4 convertase
4) MAC formation
What are the 3 types of complement cascade?
Classical, MBL, Alternative
what are the strategies that bacterial pathogens have to disrupt the complement cascade?
1) degrade complement components
2) inhibit convertases
3) recruit host-derived regulators
4) inhibit complement components
Explain in more details how bacteria degrade complement components.
Bacteria degrade C3
e.g., S.aureus and S.pyogenes
S. aureus Aur and S. pyogenes SpeB are proteases that degrade C3
This prevents…
C3b deposition
C3a formation
C5a formation
Explain in more detail how bacteria inhibit convertases.
Bacteria inhibit C3 or C5 convertases
S. aureus SCIN protein binds C3bBb and inhibits formation of C3 convertase and C5 convertase (aka blocks complement cascade and its amplification)
This prevents…
C3b deposition
C3a formation
C5a formation
Explain in more detail how bacteria recruit host derived regulators.
Bacteria recruit negative regulators.
E.g., S.aureus (recruits factor H), S.pyogenes (recruits factor H, recruits C4BP)
How do bacterial proteins prevent C3b or MAC deposition?
1) Cleave complement factors
2) Inhibit C3/C5 convertases
3) Acquire host-derived complement regulators
4) Bind complement factors and prevent their processing