Immune Evasion Flashcards
What cells are part of the innate immune system?
Neutrophils
Eosinophils
Basophils
Dendritic cells
Macrophages
What do neutrophils do?
Recruited to ares of infection
Detect microbes
Perform effector functions —> kill microbes
Why must Neutrophil responses be balanced?
To prevent infection but also to prevent damage (inflammation) to host
How do neutrophils work?
Microbes enter body and become opsonised with antibodies and complement
Results in production of gradient of C3a and C5a as well as bacterial proteins and peptides
C3a and C5a bind to their receptors on endothelial cells —> endothelial cells express ICAM at their surface
Neutrophils contact endothelial they detect increase in ICAM and adhere to ICAM receptor —> roll along surface of endothelium then transmigrate across endothelial layer
Become primed by gradient of C3a C5a/bacterial proteins and peptides
Migrate towards complementary components and bacterial proteins via chemotaxis
Become activates and perform effector functions —> phagocytosis or degranulation
Neutrophils also recruit other immune cells
What is Staphylococus aureus?
Gram positive bacterium
Commensalism and lives harmlessly in the nose
Opportunistic pathogen and able to cause minor skin infections to severe and life-threatening diseases
What is streptococcus progenies?
Gram positive bacterium
Lives harmlessly in the throat of humans
Opportunistic virus
Able to cause range of disease —> pharyngitis, skin infections, scarlet fever and sepsis
What is antibody opsonisation?
Antibodies bind bacterial antigens allowing:
—> deposition of complement in the classical complement pathway
—> neutrophils and other phagocytes the ability to detect invading microbes
What are strategies bacterial pathogens have to evade being opsonised with antibodies?
Hide antigen
Distrust function
Prevent detection
Degrade antibodies
Modify antigenicity
How are antigens hidden in evasion of antibody opsonisation?
Bacteria express capsule on their surface —> helps bind antigenic structures that can be detected by innate and adaptive immune components
How do surface proteins prevent detection in evasion of antibody sopsoinisation?
Protein bind the antibodies via their Fc region and not their Fab region —> prevents normal opsonisation
How do proteases prevent detection in evasion of antibody opsonisation?
Cleave or modify antibodies —> prevents normal opsonisation
What is the use of antigen variation in evasion of antibody opsonisation?
Switching expression of antigens means antibodies that recognise the first structure are unable to recognise those bacteria now
What is complement opsonisation?
Large number of proteins that react w/ one-another to opsonise pathogens or to directly kill them by membrane attack complex formation
What is the key step of compliment opsonisation?
Deposition of C3b onto surface of the microbe —> can be detected by complement receptors expressed on neutrophils which can phagocytose the microbe
What are the 4 key steps of the complement cascade?
Initiation
Formation of C3 convertase —> amplification of signal
Formation of C5 convertase —> formation of membrane
MAC formation
What do S. aureus and S. pyogenes SpeB do in compliment evasion?
Proteases that degrade C3
—> prevents
- C3b deposition
- C3a formation
- C5a formation
What does S. aureus SCIN do in complement evasion?
Protein binds C3bBb and inhibits formation of Cs convertase and C5 convertase
—> prevents
- C3b deposition
- C3a formation
- C5a formation
What does recruiting negative regulators do in complement evasion?
Recruitment of factor H (fH) onto surface (S.aureus) —> inactivates C3b into iCb3
Recruitment of CF binding protein 4 to surface (S. pyogenes)—> degrades C2a from Ce3 convertase
What is the goal of all evasion of complement strategies?
Ensure S.aureus is not killed by MAC + less C3b deposited onto surface of bacteria which could be detected by neutrophils and other phagocytes
How do neutrophils sense and respond to their environment?
Express hundreds of diff immune receptors at their surface or in secretory vesicles and granules
→ allow neutrophils to sense and respond to their environment
What receptors do neutrophils have?
TLR receptors —> detect conserves microbial structures
CLEC receptors —> detect microbial carbohydrates
FPR receptors —> detect formulated peptides
Through what receptors do neutrophils detect opsonised microbes?
Fc receptors or complement receptors
What do activatory receptors do?
Enhance immune cell activation
How doesS.aureus CHIPs inhibit chemotaxis and activation?
C5aR detects C5a
CHIPS blinds c5aR and prevents binding of C5a
Neutrophils do not migrate to sites of infection and do not become activated through C5aR
How does SpyCep inhibit chemotaxis?
CXCR1 and CXCR2 detect CXCL8
SpCEP cleaves CXCL* and prevents binding to CXCR1/2
Neutrophils do not migrate to sites of infection and do not become activated through CXCR1/2
How does bacteria inhibit phagocytosis?
S.aureus FLIPr inhibit Fc gamma receptors —> receptor can’t interact w/ IgG antibodies
S.aureus SSL5 inhibit Fc alpha receptors —> receptor can’t interact w/ IgA antibodies
Reduces antibody mediated phagocytosis and killing of S.aureus
How do bacteria kill neutrophils?
S. aureus —> toxins bind to receptors on neutrophils —> induce lysis
S. pyogenes —> toxins bind too cellular membrane on receptors —> cell rupture
Fewer neutrophils at sire I of infection that can detect and kill bacteria
How does bacteria inhibit effects of antimicrobials?
S.aureus express proteins that can inhibit effects of antimicrobials
