4.1 Toxins (not diseases) Flashcards
What is toxigenesis ?
ability to produce toxins
What type of toxins may bacteria produce ?
- exotoxins
- endotoxins
- where are exotoxins released from ?
- exotoxins may act on what ?
- bacterial cells
- tissue sites removed from the site of bacterial growth
What type of substances are endotoxins ?
cell-associated
Difference between gram positive and gram negative bacteria ?
Gram positive
* thick layer of peptidoglycan
* no outer membrane
* no lipopolysaccharide
* stains blue/purple on gram stain
* S. aureus, Streptococci
Gram negative
* thin layer of peptidoglycan
* presence of outer membrane
* presence of LPS
* stains pink/red on gram stain
* E.coli, salmonella spp
Example of an endotoxin
Lipopolysaccharide (LPS) on surface of bacterial cell of gram negative bacteria
When are LPS endotoxins released from Gram negative bacteria ?
- after destruction of the bacterial outer membrane
- secreted in bacterial vesicles
Why can LPS (endotoxins) be transported around the body via lymph or blood ?
because LPS is released after destruction of the bacterial outer membrane or secreted in bacterial vesicles
How can endotoxin (LPS) be transported around the body ?
lymph or blood
As endotoxins are exposed on the surface of bacteria, what has the inante immune system done to evolve ?
to recognise them as a threat and to react accordinly to their presence
Why do endotoxins provoke a strong innate immune response ?
they are pyrogens
Name the toxic componenet of endotoxins
Lipid A
What is the immune response against Lipid A mediated by ? Which expressed on what ?
TLR4 expressed on myeloid cells (e.g. macrophages)
What does TLR4 stimulate the secretion of what from macrophage and endothelial cells ?
Macrophage -> pro-inflammatory cytokines
endothelial cells -> nitric oxide
- In macrophages and monocytes what do endotoxins trigger ?
- and consequent release of what ?
- production of inflammatory cytokines
- prostaglandins
List some of the inflammatory cytokines produced by macrophages and monocytes upon being triggered by endotoxins
- IL-1
- IL-6
- IL-8
- TNF
- platelet-activating factor
- LPS endotoxins stimulates which 2 cascades ?
- Inducing what ?
- complement & coagulation cascades
- inflammation , vasodilation, chemotaxis of neutrophils, coagulation , bleeding and shock
[change Q!] In the normal host response the pro-inflammatory response (as an effect of endotoxins) is regulated and localised by what ?
a simultaneous anti-inflammatory response
List 4 effects of endotoxin
Activation of 3 …. And release of…
- macrophage activation
- release of TNF-alpha
- complement activation
- tissue factor activation
what is released in macrophage activation - as an effect of endotoxins ?
- release of IL-1 and IL-6 (proinflammatory cytokines), responsible for fever (prostaglandins)
Explain the effect of endotoxin - release of TNF-alpha
- fever
- release of nitric oxide
- hypotension
As an effect of endotoxins, the complement activation is involved to release …1. And …2.. which have separate effects, ..1…. has effect of ……3….. and ..2.. effect of …4.., …5…. And …6..
1 = C5a
2 = C3a
3 = neutrophil chemotaxis
4 = histamine release
5 = causing hypotension
6 = odema
Explain the effect of endotoxin - tissue factor activation:
Activates … results in ….
- activates coagulation cascade
- results in disseminated intravascular coagulation
How does LPS produce an inflammatory response ?
- Lipid A stimulates TLR-4 expressed on myeloid cells (e.g. macrophages)
- TLR-4 stimulation leads to production of pro-inflammatory cytokines (e.g. IL-1, IL-6, IL-8, TNF & platelet-activating factor)
- also stimulate production of prostaglandins
- complement and coagulation cascades are activated
- Inducing inflammation , vasodilation , chemotaxis of neutrophils, coagulation , bleeding & shock
- What is sepsis characterised by ?
- due to presence of what ?
- complex systemic inflammatory response
- microorganisms in the bloodstream
What are the leading causes of severe sepsis ? Give 2 examples
Gram negative bacteria
* Escherichia coli
* Pseudomonas aeruginosa
Exaggerated inflammation triggered by TLR4 during infection can lead to …?
sepsis and septic shock
Endotoxins:
* ..1… the immune system (TLR4) and is a pyrogen
* Induces massive production of …2… such as TNF-alpha leading to ..3… injuries and ….4.. failure
- activates
- proinflammatory cytokines
- inflammatory tissue
- multiorgan
What are exotoxins a group of ?
soluble proteins that are secreted by the bacterium
What effect do exotoxins have on cells ?
- destroy cells directly
- disrupt normall cellular metabolism
2 examples of exotoxins
- botulinium toxin
- tetanospasmin toxin
What do Type I exotoxins bind to and stimulate ?
bind to receptors on the cell surface and stimulate intracellular signalling pathways
- Example of type I exotoxin
- leading to what ?
- superantigens bind to MHC Class II on T cells
- leading to massive secretion of proinflammatory cytokines(Toxic Shock Syndrome by S. aureus/ S. pyogenes)
Type II exotoxins are membrane ….1… which can either form ….2.. in the target cell membrane or …3.. that act on the ..4…
- damaging
- pores
- enzymes
- membrane
Example of type II exotoxin = ..1.. released by Streptococcus pneumoniae triggers direct …2… of ..3.. epithelium and nasal …4…. epithelium (penumonia , pneumococcal invasive disease)
- pneumolysin
- cytotoxicity
- lung
- tracheobronchial
Type III exotoxins = ..1… toxins which gain access to ….2.. of target cell to exert effects
- intracellular AB
- cytoplasm
Type III exotoxin example = …1… toxin enters the ..2.. and stimulates ..3… of chloride ions pumped ….4.. the cell (Vibrio …5.., …6..)
- cholera
- cell
- ATP mediated efflux
- out of
- cholerae
- cholera
Enterotoxin:
1. act on ?
2. cause ?
- GI tract
- diarrhoea
neurotoxins:
1. act on ?
2. cause ?
- nerves or neuromuscular junction
- paralysis
pyrogenic exotoxins:
1. stimulate?
- release of cytokines
what do tissue invasive exotoxins do to invade the host ?
enzymes destroy tissue
Difference in species between exotoxin and endotoxin ?
Exo = some species of both Gram positive and gram negative
Endo = most gram-negative bacteria and Listeria
Difference in protein location between exotoxin and endotoxin ?
Exo = proteins secreted from cell
Endo = part of cell (lipopolysaccharide) that fragments off
Difference in gene location between exotoxin and endotoxin ?
Exo = in plasmid or bacteriophage
Endo = on bacterial chromosome
Difference in toxicity between exotoxin and endotoxin ?
exo = high toxicity
endo = low toxicity
Difference in antigenicity between exotoxin and endotoxin ?
exo = highly antigenic (host forms antibodies called antitoxins)
endo = poorly antigenic
Difference in availability of vaccine between exotoxin and endotoxin ?
exo = vaccine available (formed from toxoids)
endo = no vaccine available
Difference in heat stability between exotoxin and endotoxin ?
exo = heat labile (sensitive)
endo = heat stable (resistent to effect)
Difference in examples between exotoxin and endotoxin ?
exo = cholera, tetanus, botulism
endo = meningococcemia , sepsis
Toxins can cause disease in various ways , list 4 ways this includes:
- overstimulation of immune response
- cytotoxicity
- apoptosis
- disruption of cell function
List 4 disease mediated by toxins
- botulism
- tetanus
- cholera
- necrotising fasciitis
List 4 examples of toxins
- cholera toxin
- tetanospasmin
- botulinium neurotoxin
- M protein
