4.1 Toxins (not diseases) Why This Much ?? Shorten It !!

Question 1

What is toxigenesis ?

Answer 1

ability to produce toxins

Question 2

What type of toxins may bacteria produce ?

Answer 2

• exotoxins
• endotoxins

Question 3

1. where are exotoxins released from ?
2. exotoxins may act on what ?

Answer 3

1. bacterial cells
2. tissue sites removed from the site of bacterial growth

Question 4

What type of substances are endotoxins ?

Answer 4

cell-associated

Question 5

Difference between gram positive and gram negative bacteria ?

Answer 5

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

Question 6

Example of an endotoxin

Answer 6

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

Question 7

When are LPS endotoxins released from Gram negative bacteria ?

Answer 7

• after destruction of the bacterial outer membrane
• secreted in bacterial vesicles

Question 8

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

Answer 8

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

Question 9

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

Answer 9

lymph or blood

Question 10

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

Answer 10

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

Question 11

Why do endotoxins provoke a strong innate immune response ?

Answer 11

they are pyrogens

Question 12

Name the toxic componenet of endotoxins

Answer 12

Lipid A

Question 13

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

Answer 13

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

Question 14

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

Answer 14

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

Question 15

1. In macrophages and monocytes what do endotoxins trigger ?
2. and consequent release of what ?

Answer 15

1. production of inflammatory cytokines
2. prostaglandins

Question 16

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

Answer 16

• IL-1
• IL-6
• IL-8
• TNF
• platelet-activating factor

Question 17

1. LPS endotoxins stimulates which 2 cascades ?
2. Inducing what ?

Answer 17

1. complement & coagulation cascades
2. inflammation , vasodilation, chemotaxis of neutrophils, coagulation , bleeding and shock

Question 18

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

Answer 18

a simultaneous anti-inflammatory response

Question 19

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

Answer 19

• macrophage activation
• release of TNF-alpha
• complement activation
• tissue factor activation

Question 20

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

Answer 20

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

Question 21

Explain the effect of endotoxin - release of TNF-alpha

Answer 21

• fever
• release of nitric oxide
• hypotension

Question 22

As an effect of endotoxins, the complement activation is involved to release C5a and C3a what are there separate effects ?

Answer 22

C5a - neutrophil chemotaxis

C3a:
histamine release
causing hypotension
odema

Question 23

Explain the effect of endotoxin - tissue factor activation:

Activates … results in ….

Answer 23

• activates coagulation cascade
• results in disseminated intravascular coagulation

Question 24

How does LPS produce an inflammatory response ?

Answer 24

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

Question 25

1. What is sepsis characterised by ? 2. due to presence of what ?

Answer 25

1. complex systemic inflammatory response 2. microorganisms in the bloodstream

Question 26

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

Answer 26

Gram negative bacteria * Escherichia coli * Pseudomonas aeruginosa

Question 27

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

Answer 27

sepsis and septic shock

Question 28

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

Answer 28

1. activates 2. proinflammatory cytokines 3. inflammatory tissue 4. multiorgan

Question 29

What are exotoxins a group of ?

Answer 29

soluble proteins that are secreted by the bacterium

Question 30

What effect do exotoxins have on cells ?

Answer 30

* destroy cells directly * disrupt normall cellular metabolism

Question 31

2 examples of exotoxins

Answer 31

* botulinium toxin * tetanospasmin toxin

Question 32

What do Type I exotoxins bind to and stimulate ?

Answer 32

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

Question 33

1. Example of type I exotoxin 2. leading to what ?

Answer 33

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)

Question 34

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

Answer 34

1. damaging 2. pores 3. enzymes 4. membrane

Question 35

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

Answer 35

1. pneumolysin 2. cytotoxicity 3. lung 4. tracheobronchial

Question 36

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

Answer 36

1. intracellular AB 2. cytoplasm

Question 37

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

Answer 37

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

Question 38

Enterotoxin: 1. act on ? 2. cause ?

Answer 38

1. GI tract 2. diarrhoea

Question 39

neurotoxins: 1. act on ? 2. cause ?

Answer 39

1. nerves or neuromuscular junction 2. paralysis

Question 40

pyrogenic exotoxins: 1. stimulate?

Answer 40

1. release of cytokines

Question 41

what do tissue invasive exotoxins do to invade the host ?

Answer 41

enzymes destroy tissue

Question 42

Difference in species between exotoxin and endotoxin ?

Answer 42

Exo = some species of both Gram positive and gram negative Endo = most gram-negative bacteria and Listeria

Question 43

Difference in protein location between exotoxin and endotoxin ?

Answer 43

Exo = proteins secreted from cell Endo = part of cell (lipopolysaccharide) that fragments off

Question 44

Difference in gene location between exotoxin and endotoxin ?

Answer 44

Exo = in plasmid or bacteriophage Endo = on bacterial chromosome

Question 45

Difference in toxicity between exotoxin and endotoxin ?

Answer 45

exo = high toxicity endo = low toxicity

Question 46

Difference in antigenicity between exotoxin and endotoxin ?

Answer 46

exo = highly antigenic (host forms antibodies called antitoxins) endo = poorly antigenic

Question 47

Difference in availability of vaccine between exotoxin and endotoxin ?

Answer 47

exo = vaccine available (formed from toxoids) endo = no vaccine available

Question 48

Difference in heat stability between exotoxin and endotoxin ?

Answer 48

exo = heat labile (sensitive) endo = heat stable (resistent to effect)

Question 49

Difference in examples between exotoxin and endotoxin ?

Answer 49

exo = cholera, tetanus, botulism endo = meningococcemia , sepsis

Question 50

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

Answer 50

* overstimulation of immune response * cytotoxicity * apoptosis * disruption of cell function

Question 51

List 4 disease mediated by toxins

Answer 51

* botulism * tetanus * cholera * necrotising fasciitis

Question 52

List 4 examples of toxins

Answer 52

* cholera toxin * tetanospasmin * botulinium neurotoxin * M protein