2: Immune Evasion Flashcards
How are bacteria detected by the immune system
Complement system - group of proteins that opsonize or lyse bacteria
Antibodies - proteins that can opsonize bacteria
Phagocytes - immune cells that detect and kill opsonized bacteria
Key steps of complement cascade
Initiation
Generation of C3 convertase - bacterial killing by phagocytosis
Generation of C5 convertase
MAC formation - killing by lysis
3 complement pathways
classical pathway
lectin pathway
alternative pathway
Classical pathway
IgG and IgM bind to antibody - trigger
C4b and C2a form C3 convertase
Cascade reaction forming MAC
Lectin pathway
lectins (MBL and CRP) binding to pathogen - trigger
C4b and C2a form C3 convertase
Cascade reaction causing MAC
Alternative pathway
polysaccharide on bacteria surface triggers alternative pathway
C3b and Bb form C3 convertase
Cascade reaction forms MAC
Membrane Attack Complex (MAC)
result of each of the complement pathways
creates pores in pathogen membranes -> influx of fluid, cell lysis and destruction of pathogen
Antibody Opsonisation
Antibody binds to antigen
1. makes bacteria more recognisable
2. easier to engulf bacteria
triggers classical pathway of complement system
Phagocytes
engulf pathogen, contain it in phagosome and digest it using enzymes
C3b and IgG act as opsonins (tags) to mark foreign pathogen for phagocytosis
makes process more efficient
Examples of phagocytic cells
Neutrophil
Monocyte
Macrophage
Dendritic cell
Innate immunity
rapid, provides broad protection
a deficiency in complement system, lack of antibodies or phagocytes lead to impaired innate immune system
leads to an opportunity to cause infections
Immune evasion
How pathogens survive killing by immune response so they can continue to infect the host
Mechanisms of immune evasion
Avoid recognition
Inhibit phagocytosis
Kill immune cells
[ survive inside cells
disrupt immune signalling
mimic host molecules ]
Staphylococcus aureus
Gram +
Commensal in skin and mucous membranes
Opportunistic - can cause disease as MRSA ;
Skin and soft tissue infections
Osteomyelitis
Endocarditis
Bacteraemia and Sepsis
How does S. Aureus evade the complement system
Aur protease degrades C3 –> prevents C3b deposition, C3a formation
Sbi protein binding to IgG, preventing recognition by C1 –> prevents formation of C3 convertase of classical pathway
SCIN protein binds to C3bBb –> prevents formation of C3 convertase and C5 convertase
SSL7 protein binds to C5 –> prevents C5 convertase activity on C5
How does S. Aureus evade antibody response
bacteria express capsule on surface = hides antigenic structures that could be detected
Protein A bind antibodies via their Fc region not Fab region = prevents normal opsonisation
Proteases cleave or modify antibodies = prevents normal opsonisation
( CAN converts plasminogen into plasmin OR break down antibody)
What phagocytes does Alpha-toxin produced by S. Aureus kill
neutrophil
monocyte
macrophage
What phagocytes does PVL produced by S. Aureus kill
neutrophil
monocyte
macrophage
What phagocytes does LukAB produced by S. Aureus kill
neutrophil
What phagocyte does PSMs produced by S. Aureus kill
neutrophil
monocyte
macrophage
dendritic cell
Viral Immune Evasion
Virally infected cells release IFNs (interferons) which initiate antiviral state -> block replication
IFNs also activate NK cells
Many viruses escape antibody recognition by blocking IFN production
Types of interferons
Type I IFNs are IFN-a and IFN-B
Type II IFN is IFN-y ; produced by activated T-cells and NK cells
Type III IFN is IFN-λ
Natural Killer cells are activated by
IFN-a and IL-12
-kills virus-infected cells
Macrophages inactivate
opsonised virus’ , filter viral particles from blood
Dendritic cells initiate
CD4 and CD8 response
CD4 T-Cells respond to
MHC 2
CD8 T-Cells respond to
MHC 1
Neutrophil functions at site of inflammation
Pathogen recognition
pathogen clearance
cytokine secretion
