Macrophage Interactions Flashcards
Two groups of bacteria based on location where they cause disease
- Extracellular bacteria: live outside of host cells and cause disease
- Intracellular bacteria: cause disease from inside of host cells (can be cytoplasmic or phagosomal)
Strategies used by extracellular pathogens to resist killing by phagocytes
- Avoid recognition by phagocytes: invade regions ont accessible to phagocytes
- Inhibit phagocyte engulfment: Produce capsule or other anti-phagocytic determinants on surface
- Kill or damage phagocytes: secrete extracellular enzymes or toxins that damage host cell
Strategies used by intracellular pathogens to resist killing by phagocytes?
- Inhibit phagosyme-lysosyme fusion: secrete proteins that block phagosome maturation pathway
- Survive inside phagolysosome: resist degradation by acidic pH, produce enzymes able to counteact ROI and RNI radicals
- Escape from phagosome: secrete enzyme that degrade phagosomal membrane
5 functional steps of phagocytosis
- Recognition
- Uptake
- Maturation
- Killing
- Antigen presentation
Bacterial recognition
- Phagocytes recognize
- Components of bacterial cell wall or membrane
- Components of immune system following opsonization
- Bacteria can be recognized by host receptors and specific interaction can define subsequent events in steps of phagocytosis
Macrophage receptors
- PRRs recognize LPS (gram -) and LTA (gram +)
- Receptors that recognize plasma-derived molecules deposited on bacterial surface
- Receptors that recognize other signature elements on bacteria
* receptor engagement generates different host cell responses depending on receptor
Bacterial uptake
- Recognition by receptor initiates cascade-signal transduction
- Surface structure remodeled by depolymerizing and repolymerizing actin and other cytoskeletal parts
- Membrane bound phagosome
- Usually passive internalization (some bacteria actively influence internalization)
* Some bacteria employ specialized entry mechanisms to prevent phagosome maturation
Types of specialized phagocytosis
- Looping phagocytosis (Francisella)
- Coiling phagocytosis (Legionella)
Entry into non-phagocytic cells
- Trigger mechanism (major membrane perturbations)
- Zipper mechanism (minor membrane perturbations)
Trigger mechanism
- Salmonella
- Major cytoskeleton remodeling; promoted by bacterial effector proteins injected into host cell
- promoted by bacterial effector proteins injected into the host cells
Zipper mechanism
- Listeria
- Minimal cytoskeleton remodeling; Bacteria “slide” into cell - involves bacterial proteins
- minor membrane perbutations
Maturation of bacteria-containing phagosomes
- Fusion with endocytic vesicles
- Classified as either early endosomes or late endosomes (depending on proteins on surface)
- Lysosome fuses with endosme = phagolysosome
Microtubules
Cytoskeletal components that allow maturation of the phagosome from the periphery to perinuclear region
Macrophage activation reduces ability of bacteria to _____ _______
Alter maturation
How do bacteria alter phagosome trafficking? (4)
- Survive and replicate in phagolysosome
- Escape and replicate in cytosol
- Modulate endocytic pathway
- Alternative trafficking pathway
Bacterial killing by lysosomes
- Oxygen dependent killing
- generate nitric oxide
- NADPH oxidase - generate super oxide
- Oxygen independent killing
- Lower pH (phagolysosome)
Processing of bacterial antigens
- Antigens degraded into oligopeptides (13-18 AA)
- Binding to class I or II MHC
- Antigen presentation on surface
- Stimulation of T-Cell
