Immune evasion by microbes Flashcards
What are the innate immune cells?
Neutrophils, Eosinophils, Basophils, Dendritic cells, Macrophages
Why must neutrophil response be balanced?
So that infection is prevented but also damage is prevented to the host (inflammation)
What is opsonisation?
Where a pathogen is marked for ingestion and destruction by phagocytes
What do neutrophils do?
- Opsonisation occurs
- Gradient of C3a and C5a and bacterial proteins is made
- Results in neutrophil recruitment:
- C5a binds to C5aR
- C3a binds to C3aR
- Endothelial cells express ICAM
- Neutrophils rolls along surface of vessels (adhesion) - The neutrophils migrate across the endothelial barrier
- The gradient of C3a, C5a and bacterial proteins ‘PRIMES’ the neutrophils
- Chemotaxis occurs, where the neutrophils migrate to the complement proteins and bacterial proteins where they become ACTIVATED
7a. They perform their effector function by ingestion adn phagocytosing the pathogen/bacteria
OR
7a. They become degranulated by releasing antimicrobial molecules
7b. They recruit other immune cells to the site of infection
What type of bacteria is S.aureus?
Gram-positive, it is opportunistic
What 3 methods does S.aureus use to evade antibody opsonisation?
- The bacterium expresses a polysaccharide capsule which hides the antigens on the surface membrane so that they cannot be bound to (or less efficiently) by antibodies, therefore there is a lower amount of complement being deposited on the surface of the bacteria.
- Protein A (SpA) causes antibodies to bind via their Fc region rather than the Fab region which means complement cannot be deposited on the bacterial surface. Can also be done by Sbi protein
- The bacterium secretes SSL10 which binds to the Fc region of an antibody after it has already bound the bacterium via its Fab region. This results in the antibody being unable to be detected by Fc receptors on neutrophils
What antibody evasion strategies are there besides the ones that S.aureus is able to do?
- Proteases from bacteria cleave antibodies (Fc and Fba are separated)
- Antigenic Variation - Bacteria switch the anitbodies being presented so less opsonisation occurs
What is the classical complement cascade?
- Deposition of antibodies
- Formation of C1qrs
- Activation of C3 convertase (C4bC2b)
- Formation of C5 convertase
- Deposition of C6-9 on membrane and formation of membrane attack complex
What is the MBL complement cascade?
- Formation of MBL + MASP
- Activation of C3 convertase (C4bC2b)
- Formation of C5 convertase
- Deposition of C6-9 on membrane and formation of membrane attack complex
What is the alternative complement cascade?
- Deposition of C3b onto microbe surface
- Activation of C3 convertase (C3bBb)
- Formation of C5 convertase
- Deposition of C6-9 on membrane and formation of membrane attack complex
What does the SCIN protein from S.aureus do?
Binds to the C3bBb and inhibits the formation of C3 and C5 convertases
This prevents :
- C3b deposition onto cell microbe surfaces
- C3a formation
- C5a formation
What does the Efb protein from S.aureus do?
Binds to C3d in C3, which causes a conformation change
This prevents:
- Factor B from binding to C3
- C3dg binding to CR2 (complement receptor 2)
What do TLR receptors detect?
Conserved microbial structures such as:
- LPS in gram negative cell wall
- LTA in gram positive cell wall
- Flagella
What do CLEC receptors detect?
Microbial carbohydrates
What do FPR receptors detect?
Formylated peptides released from pathogens
