1. Toxins

Front 1

What are toxins?

Back 1

-Toxins are microbial products that can damage the host
-Toxins can cause disease independent of the bacterium
-For example, pathogenic bacteria can be killed in a patient but the disease may persist due to the continued action of the toxin

Front 2

What are exotoxins?

Back 2

-Secreted proteins made by both Gram + and Gram - bacteria
-May enter the blood circulation and spread to parts of the body and cause damage far from the site of bacterial colonization

Front 3

What are the three main categories of exotoxins?

Back 3

1) Cytolytic toxins (these attack the cell constituents causing cell lysis
2) Neurotoxins (specifically interfere with nerve cell function
3) Enterotoxins - these affect cells lining the GI tract causing massive fluid secretion (diarrhoea, ex: cholera toxin)

Front 4

How potent are exotoxins?

Back 4

-Extremely potent molecules
-Small dose can have a significant effect on the host
-Since exotoxins are protein; they are usually heat labile (actively destroyed by heating 60-80 degrees)
-Immmunogenic (stimulates the immune system to produce neutralizing antibodies)

Front 5

Can we vaccinate against toxin mediated diseases?

Back 5

Yes
-We do this through immunization with toxoids
-Toxoids are toxins that have been treated with heat or chemicals to make them non-toxic to the patient but still capable of stimulating the production of neutralizing antibodies

Front 6

What are endotoxins?

Back 6

-These are released only when the bacteria die or are digested by phagocytic cells
-Endotoxins are usually equated with LPS which is present in outer membrane of Gram - bacteria
-Gram positive bacteria produce molecules with similar properties (LTA)

Front 7

What are the properties of endotoxins?

Back 7

-They are non-protein molecules and are generally heat stabile
-Endotoxins act through binding to a conserved pattern recognition receptor (Toll like receptor 4) on macrophages - this leads to signal transudction and activation of a transcription factor NF-kB
-Endotoxins elicits a lot of its symptoms through its induction of the inflammatory response

Front 8

What do endotoxins do?

Back 8

They activate macrophages causing release of inflammatory cytokines (tumor necrosis factor)
-In low doses patient might experience fever (endotoxin is pyrogenic), malaise, aches and pain
-In higher doses it can cause damage to circulatory system and shock

Front 9

what is endotoxin shock?

Back 9

-Fluids leak out of blood vessels, blood coagulates and blood pressure drops
-Organs fail and death may result

Front 10

How do we treat endotoxin shock

Back 10

-Supportive therapy
-Antibiotics are not used because they can cause LPS/endotoxin release
-We use Xigris which reduces mortaliy but we don't know the mode of action
-It appears to combine anticoagulant and anti-inflammatory properties
-Vaccine cannot be used since endotoxins are non-protein molecules and they are not very immunogenic