Bacterial infection 3 Flashcards
Innate immune response
Rapid, general, always on
Non-specific
Physical and chemical barriers
Can target infected host cells
Adaptive immune response
Slower, specific, memory
React to antigens
Generates antibodies
Forms immune memory ice pathogen encountered
Can target infected host cells
MAMPs
Microbe-associated molecular patterns
PRRs
Pattern recognition receptors
TLRs
- means?
- e.g?
Toll-like receptors
e.g. TLR4 binds LPS
Innate immune cells
Macrophages
PMNs
= Polymorphonuclear lymphocytes
e.g. neutrophils
Dendritic cells
Mast cells
Monocytes
Macrophages
Resident in tissues
1st to encounter pathogen
Secrete cytokines
- can make blood vessels more leaky
- > let neutrophils out
- conc grad
- > directs neutrophils
Communicate w/ adaptive IS
-> present antigens (APC)
Oxygen-independent killing
Lysozyme
AMPs
-antimicrobial peptides
Oxygen-dependent killing
Activated by TLRs
Free radical production
Oxidative burst
(great increase in O2 consumption)
Phagocyte
Cell capable of phagocytosis
e.g. macrophage, neutrophil
Phagolysosome
Lysosome deposits enzymes into phagosome
-> cleaves macromolecules + generates ROS
= destroys pathogen
NETs
= Neutrophil Extracellular Traps
- release their DNA saturated w/ antimicrobials into surroundings
- > traps + kills bacteria
-> Easier for macrophages to engulf
Immune evasion strategies
Stealth
= avoids triggering immune response
Subversion
= manipulate, divert, dampen responses
Resistance
= Vary targets to avoid recognition
- could directly destroy immune effectors
Extracellular pathogens must survive…:
Phagocytosis
Antimicrobial peptides
Lysozyme
Mucus shedding
Attachment mechanisms can contribute to avoidance…
- when?
- eg?
In pathogens that remain on mucus membrane
e. g. EPEC pedestal formation
- prevents phagocytosis
Antimicrobial peptides
e. g. Defensins
- kill bacteria entering crypts to protect stem cells + avoid infection
Bind to bacterial membranes
> form pores + rupture membrane
OR
> enter cell + inhibit functions
Antimicrobial protein resistance
EPEC produce OmpT protease
= Outer Membrane Protease
degrade antimicrobial proteins
Biofilms
Surface-associated multicellular communities
Cells embedded in exopolymeric matrix
Biofilms
-protection
Protect from AMPs, lysozyme + mechanical clearance
Stealth
- 3 strategies
> Avoid triggering response
Hide from IS
Mask antigens +/or mimic host ‘self’ antigens
Stealth
- masking antigens
Salmonella LPS
- detected by immune cells
S.typhi
- no IS response
- SP17 (PAI) encodes a capsule
- > masks LPS
Capsules
- roles
Contains sialic acid residues
- mimic host cells
= prevents phagocytosis
Binds to antimicrobial peptides + complement proteins
- keeps them way from target site
Opsonisation
- Abs bind to capsules to help phagocytosis
Shields antigens/LPS from immune receptors
-> prevents activation of ROS killing + reduces cytokine production
Phase variation
Phenotypic variation in a population
- heritable but reversible
Normally affects surface-exposed antigens
ON/OFF switch by promoter inversion
Antigenic variation
Not ON/OFF
- range of possible variants
Cell has genetic info to express range on antigenically distinct proteins
-> BUT only expresses 1 at a time
Changes arise via recombination between variable gene regions
