Microbial Decoys Flashcards
(18 cards)
What are 4 strategies used by microbes to avoid antibodies/complement?
- Blocking antibodies from binding
- Destroying antibodies
- Hijacking host immune regulators
- Neutralising immune signals
How does Neisseria meningitidis and Streptoccus pneumoniae subvert complement?
Through hijacking human Factor H
What is human factor H?
A negative regulator of complement
How does How does Neisseria meningitidis and Streptoccus pneumoniae hijack Factor H?
Bind Factor H to their surface; mimicking self; prevents complement activation
What is IgA1 protease?
Enzyme that cleaves IgA1, a dominant antibody in mucosal areas.
Weakens mucosal defence, e.g. in respiratory tract
What pathogens secrete IgA1 proteases?
Streptococcus pneumoniae
Neisseria spp.
What is protein A?
- Binds to Fc region of IgG; prevents Fc receptor recognition by phagocytes
- Induces B cell apoptosis
What pathogen uses protein A?
Staphylococcus aureus
What is SSL7?
S. aureus superantigen-like protein 7.
- Binds to Fc region of IgA; blocks IgA receptor interaction.
- Also binds C5; inhibits complement activation
What is an example of a pathogen that has a carbohydrate capsule?
Streptococcus pneumoniae
What is the immune evasion granted by S. pneumoniae capsule?
- Block phagocyte receptors
- Carbohydrate capsules are not well recognised by immature immune systes (e.g. babies)
- S. pneumoniae has over 90 serotypes; evades immunity & vaccine targetting
How can conjugate vaccines help tackle capsules?
Link capsule polysaccharide to protein to boost immunogenicity
How many serotypes do S. pneumoniae vaccines cover?
Only the most common 7.
This leads to serotype replacement post-vaccination (rarer serotypes fill ecological niche)
What pathogen has a glycan shield?
HIV; envelope of heavily glycosylated proteins
Where are glycans derived from?
The host (“self”); evades antibody detection
What happens to the glycan shield of HIV over time?
- Addition of glycosylation sites to gp120; further masks viral epitopes
- Altering of loop sequencing; further reduces antibody accessibility to binding sites
- Together, they combine to provide rapid antigenic variation
What did Sager et al. find about glycosylation and altered loop structures?
Significantly reduced antibody neutralisation capability
How does SARS-CoV-2 decrease vaccine efficacy?
Variants in mutations in Spike protein lead to antigenic drift; decreased vaccine efficacy