Exotoxins

Question 1

define pathogen

Answer 1

A microorganism capable of causing disease.

Question 2

define pathogenicity

Answer 2

The ability of an infectious agent to cause disease

Question 3

define virulence

Answer 3

The quantitative ability of an agent to cause disease

Question 4

how are many toxins encoded?

Answer 4

extrachromosomal genes
Plasmids – Bacillus anthracis toxin, tetanus toxin
Lysogenic bacteriophage – e.g. streptococcal pyrogenic exotoxins in Scarlet Fever, Diphtheria toxin.
allows presence of toxin to be transferred

Question 5

how are toxins classified?

Answer 5

Membrane Acting Toxins – Type I (can be internalised)
Membrane Damaging Toxins – Type II
Intracellular Toxins – Type III (tamper with intracellular signalling and metabolic pathways bsc killing it)

-> always changing according to new knowledge

Question 6

recall features of membrane acting toxins

Answer 6

Act from without the cell.
Interfere with host cell signaling by inappropriate activation of host cell receptors
Target receptors include:
Guanylyl cyclase ➡️ intracellular cGMP
Adenyl cyclase ➡️ intracellular cAMP
Rho proteins
Ras proteins

Question 7

recall features of membrane damaging toxins

Answer 7

get into membrane by receptor interaction and produce pool/tunnel by polymerising which damages osmolality of host cell.
Insert channels into host cell membrane.
β sheet toxins e.g. S.aureus α – toxin, 𝛾 toxin, PVL
α helix toxins – e.g. diphtheria toxin
Enzymatical damage e.g. S. aureus β- haemolysin, PSM
OR
Receptor mediated
Receptor Independent

Question 8

recall features of A-B toxins (III)

Answer 8

intracellular toxins
receptor mediated endocytosis allows toxin access
A-component damage cellular process
B-comoponents = electrostatic interactions which allow binding and translocation/ involved in endocytosis

Question 9

state the different varieties of enzymatic component A involved in A-B toxins

Answer 9

ADP – ribosyl transferases - e.g. Exotoxin A of Pseudomonas aeruginosa, pertussis toxin.
Glucosyltransferases – e.g. TcdA and TcdB of Clostridium difficile
Deamidase – e.g. dermonecrotic toxin of Bordetella pertussis.
Protease – e.g. Clostridial neurotoxins: botulism & tetanus
Adenylcyclase - e.g. EF (Edema factor) toxin of Bacillus anthracis

Question 10

Understand what is an endotoxin, its structure, function, and contribution to disease

Answer 10

• gram negative only
  LIPID A.
• Phosphorylated glucosamines attached to long chain fatty acids.
• Number and type of fatty acid vary by species.
• Hydrophobic
  POLYSACCHARIDE CORE
• Ketodeoxyoctanoic acid (KDO) and heptose.
• Relatively constant between species
• Hydrophilic
  + variable hydrophilic 0 side chain

Question 11

Compare endotoxins with exotoxin.

Answer 11

EXO: - three types
+ and - derivatives
can padlock MHCII and TCR causing exotoxin immune disregulation (receptor interaction)

ENDO: one type
- membrane interaction
- only derivatives in cell wall
- interferes with innate immune response

Question 12

Define sepsis

Answer 12

Life threatening organ dysfunction caused by a dysregulated host response to infection
ROS = causes cell damage
⬆️membrane permeability and tf expression causing immunothrobosis
damage to mtDNA = decreased intracellular ATP = cell death/ hibernation

Question 13

Understand the role of endotoxin in sepsis by investigating Meningococcal sepsis.

Answer 13

• gram -tive diplococci
  various serotypes : A.B.C.Y. W135
• life threatening
• active endotoxin: blebs are membrane capsules overfilled with endotoxin with high extensive transmission = dis regulated activation = sepsis and thrombosis, oedema