Microbial Immune Evasion Mechanisms Flashcards
What are the microbial components that drive the pathogenesis of disease?
- Adhesins
- Toxins
- Capsules
What are the properties of the host defensive mechanisms
- Natural barriers
- Defensive cells
- Complement
- immune response
What is virulence?
The degree to which a pathogen causes disease
What are the roles of virulence factors?
Colonisation and adhesion
- Promoting adherence
- Promote receptor binding
- Promote internalisation of viruses
- Allow bacterial colonisation of mucosal surfaces
Promote Tissue damage
- Production of toxins and enzymes
- pharmacological cytopathic action
Evade host defences
How does each pathogen evade the immune defenses?
There are over 300 human pathogens that are dealt with different immune mechanisms - each pathogen tries to evade different parts of innate immune system
How do bacteria evade the immune response?
Bacteria try to overcome the complement system
What are the roles of the complement system?
- induces inflammatory response
- promotes chemotaxis
- ↑ phagocytosis by opsonisation
- ↑vascular permeability
- mast cell degranulation
- lysis of cell membranes
How does the complement system achieve its roles?
Releases factors that chemo attract effector cells e.g. macrophages, neutrophils
How do bacteria overcome the complement system?
- Failure to trigger complement cascade -ve binding
2. Block/expel MAC
How do bacteria inhibit complement cascade activation?
LPS, capsules inhibit early stages of complement to bind to their surfaces
Stops assembly of complex on surfaces; Factor H sequestration
Coating with non-fixing IgA - can’t be opsonized
How do bacteria block macrophages?
- Capsule blocks C3b binding (potent opsonin)
- Capsule prevents C3b receptor access
- C5a proteases (C5a is a chemoattractant factor)
Give examples of intracellular pathogens
Mycobacterium tuberculosis
Listeria
Salmonella
How do intracellular pathogens evade immune response?
Hidden from serum killing, complement, antibodies by hiding in a host cell
What are leukocidins?
cytotoxin created by some types of bacteria that forms pores in cells to kill them - cytopathic
e.g. Staphylococcus
How do intracellular pathogens prevent opsonisation?
Protein A (binds Fc portion of IgG)
How do intracellular pathogens block contact with immune cells?
capsules
meningococcus, Hib
Outline the immune evasion mechanisms in intracellular pathogens
promote own uptake (safe)
- CR3; mannose lectin receptors
Prepares cell for invasion: Shigella
-ve P-L fusion: M. tuberculosis
Escape P-L to cytoplasm: Listeria
Resist oxidative killing
Produce catalases/peroxidases
How does TB evade immune mechanisms
TB evades phagolysosome fusion
Remains as an early non-acidified vacuole in which bacteria can replicate to v. high no.’s and infect other cells to cause disease
Describe the characteristics of antibodies
Antibodies are antigen specific, high affinity
How do antibody-antigen complexes work?
Fc receptors (on macrophage) bind to a bacteria Fc component
Bateria is internalised and killed due to antibody generation
> Fc receptor mediated phagocytosis