4.1 Toxins (not diseases) Flashcards

1
Q

What is toxigenesis ?

A

ability to produce toxins

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2
Q

What type of toxins may bacteria produce ?

A
  • exotoxins
  • endotoxins
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3
Q
  1. where are exotoxins released from ?
  2. exotoxins may act on what ?
A
  1. bacterial cells
  2. tissue sites removed from the site of bacterial growth
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4
Q

What type of substances are endotoxins ?

A

cell-associated

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5
Q

Difference between gram positive and gram negative bacteria ?

A

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

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6
Q

Example of an endotoxin

A

Lipopolysaccharide (LPS) on surface of bacterial cell of gram negative bacteria

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7
Q

When are LPS endotoxins released from Gram negative bacteria ?

A
  • after destruction of the bacterial outer membrane
  • secreted in bacterial vesicles
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8
Q

Why can LPS (endotoxins) be transported around the body via lymph or blood ?

A

because LPS is released after destruction of the bacterial outer membrane or secreted in bacterial vesicles

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9
Q

How can endotoxin (LPS) be transported around the body ?

A

lymph or blood

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10
Q

As endotoxins are exposed on the surface of bacteria, what has the inante immune system done to evolve ?

A

to recognise them as a threat and to react accordinly to their presence

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11
Q

Why do endotoxins provoke a strong innate immune response ?

A

they are pyrogens

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12
Q

Name the toxic componenet of endotoxins

A

Lipid A

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13
Q

What is the immune response against Lipid A mediated by ? Which expressed on what ?

A

TLR4 expressed on myeloid cells (e.g. macrophages)

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14
Q

What does TLR4 stimulate the secretion of what from macrophage and endothelial cells ?

A

Macrophage -> pro-inflammatory cytokines
endothelial cells -> nitric oxide

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15
Q
  1. In macrophages and monocytes what do endotoxins trigger ?
  2. and consequent release of what ?
A
  1. production of inflammatory cytokines
  2. prostaglandins
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16
Q

List some of the inflammatory cytokines produced by macrophages and monocytes upon being triggered by endotoxins

A
  • IL-1
  • IL-6
  • IL-8
  • TNF
  • platelet-activating factor
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17
Q
  1. LPS endotoxins stimulates which 2 cascades ?
  2. Inducing what ?
A
  1. complement & coagulation cascades
  2. inflammation , vasodilation, chemotaxis of neutrophils, coagulation , bleeding and shock
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18
Q

[change Q!] In the normal host response the pro-inflammatory response (as an effect of endotoxins) is regulated and localised by what ?

A

a simultaneous anti-inflammatory response

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19
Q

List 4 effects of endotoxin
Activation of 3 …. And release of…

A
  • macrophage activation
  • release of TNF-alpha
  • complement activation
  • tissue factor activation
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20
Q

what is released in macrophage activation - as an effect of endotoxins ?

A
  • release of IL-1 and IL-6 (proinflammatory cytokines), responsible for fever (prostaglandins)
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21
Q

Explain the effect of endotoxin - release of TNF-alpha

A
  • fever
  • release of nitric oxide
  • hypotension
22
Q

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..

A

1 = C5a
2 = C3a
3 = neutrophil chemotaxis
4 = histamine release
5 = causing hypotension
6 = odema

23
Q

Explain the effect of endotoxin - tissue factor activation:

Activates … results in ….

A
  • activates coagulation cascade
  • results in disseminated intravascular coagulation
24
Q

How does LPS produce an inflammatory response ?

A
  1. Lipid A stimulates TLR-4 expressed on myeloid cells (e.g. macrophages)
  2. TLR-4 stimulation leads to production of pro-inflammatory cytokines (e.g. IL-1, IL-6, IL-8, TNF & platelet-activating factor)
  3. also stimulate production of prostaglandins
  4. complement and coagulation cascades are activated
  5. Inducing inflammation , vasodilation , chemotaxis of neutrophils, coagulation , bleeding & shock
25
Q
  1. What is sepsis characterised by ?
  2. due to presence of what ?
A
  1. complex systemic inflammatory response
  2. microorganisms in the bloodstream
26
Q

What are the leading causes of severe sepsis ? Give 2 examples

A

Gram negative bacteria
* Escherichia coli
* Pseudomonas aeruginosa

27
Q

Exaggerated inflammation triggered by TLR4 during infection can lead to …?

A

sepsis and septic shock

28
Q

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

A
  1. activates
  2. proinflammatory cytokines
  3. inflammatory tissue
  4. multiorgan
29
Q

What are exotoxins a group of ?

A

soluble proteins that are secreted by the bacterium

30
Q

What effect do exotoxins have on cells ?

A
  • destroy cells directly
  • disrupt normall cellular metabolism
31
Q

2 examples of exotoxins

A
  • botulinium toxin
  • tetanospasmin toxin
32
Q

What do Type I exotoxins bind to and stimulate ?

A

bind to receptors on the cell surface and stimulate intracellular signalling pathways

33
Q
  1. Example of type I exotoxin
  2. leading to what ?
A
  1. superantigens bind to MHC Class II on T cells
  2. leading to massive secretion of proinflammatory cytokines(Toxic Shock Syndrome by S. aureus/ S. pyogenes)
34
Q

Type II exotoxins are membrane ….1… which can either form ….2.. in the target cell membrane or …3.. that act on the ..4…

A
  1. damaging
  2. pores
  3. enzymes
  4. membrane
35
Q

Example of type II exotoxin = ..1.. released by Streptococcus pneumoniae triggers direct …2… of ..3.. epithelium and nasal …4…. epithelium (penumonia , pneumococcal invasive disease)

A
  1. pneumolysin
  2. cytotoxicity
  3. lung
  4. tracheobronchial
36
Q

Type III exotoxins = ..1… toxins which gain access to ….2.. of target cell to exert effects

A
  1. intracellular AB
  2. cytoplasm
37
Q

Type III exotoxin example = …1… toxin enters the ..2.. and stimulates ..3… of chloride ions pumped ….4.. the cell (Vibrio …5.., …6..)

A
  1. cholera
  2. cell
  3. ATP mediated efflux
  4. out of
  5. cholerae
  6. cholera
38
Q

Enterotoxin:
1. act on ?
2. cause ?

A
  1. GI tract
  2. diarrhoea
39
Q

neurotoxins:
1. act on ?
2. cause ?

A
  1. nerves or neuromuscular junction
  2. paralysis
40
Q

pyrogenic exotoxins:
1. stimulate?

A
  1. release of cytokines
41
Q

what do tissue invasive exotoxins do to invade the host ?

A

enzymes destroy tissue

42
Q

Difference in species between exotoxin and endotoxin ?

A

Exo = some species of both Gram positive and gram negative

Endo = most gram-negative bacteria and Listeria

43
Q

Difference in protein location between exotoxin and endotoxin ?

A

Exo = proteins secreted from cell

Endo = part of cell (lipopolysaccharide) that fragments off

44
Q

Difference in gene location between exotoxin and endotoxin ?

A

Exo = in plasmid or bacteriophage

Endo = on bacterial chromosome

45
Q

Difference in toxicity between exotoxin and endotoxin ?

A

exo = high toxicity

endo = low toxicity

46
Q

Difference in antigenicity between exotoxin and endotoxin ?

A

exo = highly antigenic (host forms antibodies called antitoxins)

endo = poorly antigenic

47
Q

Difference in availability of vaccine between exotoxin and endotoxin ?

A

exo = vaccine available (formed from toxoids)

endo = no vaccine available

48
Q

Difference in heat stability between exotoxin and endotoxin ?

A

exo = heat labile (sensitive)

endo = heat stable (resistent to effect)

49
Q

Difference in examples between exotoxin and endotoxin ?

A

exo = cholera, tetanus, botulism

endo = meningococcemia , sepsis

50
Q

Toxins can cause disease in various ways , list 4 ways this includes:

A
  • overstimulation of immune response
  • cytotoxicity
  • apoptosis
  • disruption of cell function
51
Q

List 4 disease mediated by toxins

A
  • botulism
  • tetanus
  • cholera
  • necrotising fasciitis
52
Q

List 4 examples of toxins

A
  • cholera toxin
  • tetanospasmin
  • botulinium neurotoxin
  • M protein