Foundation quick editor Flashcards
What is the difference in adherence between commensals and pathogenic bacteria?
Commensals - loosely associated with mucosa
Pathogens - adhere closely
How do bacteria adhere to tissue?
surface proteins:
- non-fimbriate adhesins (eg on outer membrane proteins in G-)
- Fimbriae
- these are specific for certain tissues (eg E. coli have p. pilli, specific to GU tract)
- bind the oligosaccharide on host-cell glycoproteins
Entry of bacteria into host - what are the mechanisms?
Give an example
Which organisms forego this altogether?
Only some bacteria enter host - eg ETEC, Cholera just secrete toxins
Adhesion/invasion molecules are often the same - the host determines the response (cell takes the bacteria in)
Mechanisms: Pathogen-mediated endocytosis
- cell is tricked into taking it up
- Initiated by bacterial surface proteins - sometimes fimbriae, binding triggers change in the cell to take in the bacteria
Example: Yersinia + M cells
- Yersinia have invasin surface protein
- invasin binds integrin on M cell
- this sends signal through host membrane to produce change in the cytoskeleton -> invasion
What happens after a bacteria invades (2)
(1) May stay in the epithelium
- eg Shigella - which reinvades epithelium from the other side
(2) translocation (most bacteria)
- encounter non-specific immune mechanisms:
- extracellular -> must evade phagocytosis
- intracellular -> must reisist intracellular killing, but are safe from phagocytosis
How might bacteria evade phagocytosis? (3 big methods)
(1) Direct effects on phagocytes
- produce leukocidins - kill them (eg S. aureus)
- produce anti-inflammatory toxins/enzymes - stop inflammation
(2) Evade opsonisation
- capsule - may resemble host components (eg S pyogenes = hyaluronic acid)
- capsule masks PAMPs so can’t opsonise
- capsule - electrostatic repulsion ( both we + capsule are neg charge)
(3) Evade killing once phagocytosed
- inhibit respouratory burst
- prevent phagolysosome formation
- esape phagocytic vacuole
- resist bactericidal systems
What are some methods that phagocytes use to kill bactiera (3)
- lysosomal enzymes/defensins
- reactive O2 intermediates
- nitric oxide
What are some strategies pathogens use to evade adaptive immunity? (4)
Direct immunosuppression (HIV, pertussis)
Expression of weak antigens
Antigenic diversity (eg diff capules across spp)
Antigen modification (individual bacteria change antigen)
What are 3 main methods of tissue damage by bacteria
direct toxicity
induction of cytokines
induction of immunopathology
How may bacteria produce tissue damage through direct toxicity?
Exotoxins
Endotoxins
What are the differences between exotoxins + endotoxins
- origin, structure
- chemical nature
- heat resisitance
- antigenicity, response by imm system
- potency
- toxoids
- mode of action
Exotoxins are secreted by bacteria, Endotoxins are a natural structural compound released when cells die
Chemical nature:
- exotoxins - protein
- endotoxins - LPS
Heat resistance
- exotoxins - vary
- endotoxins - high
Antigenicity
- exotoxins - high, can be neutralised by antibodies
- endotoxins - varies, can’t be neutralised by antibodies
Potency
- exotoxin - v high
- endotoxin - moderate
toxoids (antigenic but not toxic)
- exotoxins - we can make them
- endotoxins - none
mode of action
- exotoxin - highly specific
- endotoxin - non-specific
Where can toxins act
- extracellularly
Extracellularly
- on intact host cells - haemolysin, leucosidins
- on ECM - hyaluronidase, collagenase (eg gas gangrene)
- other host molecules - lipin, fibrin, nucleic acids
Intracellularly
- cytotoxic - inhibit growth = diphtheria toxin, shiga toxin
- cytotonic - stimulate - cholera enterotoxin, heat-stable enterotoxin
What are some toxin-mediated diseases
Staph food poisoning botulism tetanus diphtheria staph TSS enterotoxigenic diarrhoea (eg cholera)
What are 3 ways that induction of cytokines occurs in bacterial disease
Stimulation of immune system with PAMPs
Direct action of secreted toxin on immune cells
- eg endotoxin - pyrogenic, activates complement, etc.
Effect of superantigens
What do the following PRR recognise? TLR2 TLR3 TLR4 TLR5 TLR9
TLR2 - peptidoglycan TLR3 - viral dsRNA TLR4 - LPS - outer membrane of G- TLR5 - flagellin TLR9 - bacterial DNA
what happens when PRR recognises a PAMP
signal to cell -> change gene transcription -> produce inflammatory mediators
