BACTERIAL TOXIN STUDY GUIDE WITH PREVENTION OF
INFECTION
Prevention of infection by vaccination
i. During infection, the immune system recognizes specific components of
bacteria & produces antibodies
ii. Antibodies give immunity to subsequent infection (specific immunity)
iii. Opsonisation (directly & via complement)
iv. Complement-mediated lysis (gram-negative)
v. Direct neutralization of virulence factors
vi. Vaccines ‘trick’ the immune system to respond by using ‘harmless’
components resembling infecting bacteria
vii. On contact with bacteria following immunisation the immune system
is now primed to attack
viii. Only a limited number of components can induce protective immunity
• SPECIFIC PROTECTIVE BACTERIAL COMPONENTS
MUST BE IDENTIFIED TO DEVELOP EFFECTIVE
VACCINES
What are bacterial toxins?
i. Lipopolysaccharide (endotoxin)
ii. Gram-negative bacteria only
iii. Bacterial protein toxins
(exotoxins)
iv. Gram-positive & some gram-negative bacteria
v. Capsular polysaccharides
Endotoxin (endogenous)
• Lipopolysaccharide – part of the structure of the gram-negative
bacterial outer membrane
• Only one type of endotoxin, similar in all gram negatives
• Lower potency than exotoxins (>100 less potent)
, • Can cause fever (pyogenic)
• CAN NOT be converted into a toxoid; NOT suitable as a vaccine component
The many activities of lipopolysaccharide (endotoxin)
i. Release of cytokines from various cells (monocytes, macrophages,
lymphocytes)
ii. – leads to fever & inflammation
iii. Complement system also activates - inflammation
iv. Damage to capillary blood vessels; fluid leaks into tissues causing a
severe drop in blood pressure ‘shock’
v. Endotoxin can also cause non-specific blood coagulation leading to
thrombus formation & blockage of small blood vessels in vital organs
(brain, liver, kidney), known as disseminated intravascular coagulation
(DIC)
Neisseria meningitidis (the meningococcus)
i. During growth outer membrane ‘blebs’ released
ii. Blebs contain lipopolysaccharide (endotoxin)
iii. Lipopolysaccharide (LPS) mediates inflammation & septic shock
iv. Meningococcal infection => septicemia
Exotoxins (extracellular protein toxins)
i. Proteins secreted by many gram-positive & some gram-negative bacteria
ii. Many different exotoxins known to exist
iii. Direct effect on virulence
iv. May be responsible for entire symptoms of infection
v. Most toxic substances are known (1ug kills 103 guinea pigs)
vi. Possible target for neutralizing
antibodies Cholera
INFECTION
Prevention of infection by vaccination
i. During infection, the immune system recognizes specific components of
bacteria & produces antibodies
ii. Antibodies give immunity to subsequent infection (specific immunity)
iii. Opsonisation (directly & via complement)
iv. Complement-mediated lysis (gram-negative)
v. Direct neutralization of virulence factors
vi. Vaccines ‘trick’ the immune system to respond by using ‘harmless’
components resembling infecting bacteria
vii. On contact with bacteria following immunisation the immune system
is now primed to attack
viii. Only a limited number of components can induce protective immunity
• SPECIFIC PROTECTIVE BACTERIAL COMPONENTS
MUST BE IDENTIFIED TO DEVELOP EFFECTIVE
VACCINES
What are bacterial toxins?
i. Lipopolysaccharide (endotoxin)
ii. Gram-negative bacteria only
iii. Bacterial protein toxins
(exotoxins)
iv. Gram-positive & some gram-negative bacteria
v. Capsular polysaccharides
Endotoxin (endogenous)
• Lipopolysaccharide – part of the structure of the gram-negative
bacterial outer membrane
• Only one type of endotoxin, similar in all gram negatives
• Lower potency than exotoxins (>100 less potent)
, • Can cause fever (pyogenic)
• CAN NOT be converted into a toxoid; NOT suitable as a vaccine component
The many activities of lipopolysaccharide (endotoxin)
i. Release of cytokines from various cells (monocytes, macrophages,
lymphocytes)
ii. – leads to fever & inflammation
iii. Complement system also activates - inflammation
iv. Damage to capillary blood vessels; fluid leaks into tissues causing a
severe drop in blood pressure ‘shock’
v. Endotoxin can also cause non-specific blood coagulation leading to
thrombus formation & blockage of small blood vessels in vital organs
(brain, liver, kidney), known as disseminated intravascular coagulation
(DIC)
Neisseria meningitidis (the meningococcus)
i. During growth outer membrane ‘blebs’ released
ii. Blebs contain lipopolysaccharide (endotoxin)
iii. Lipopolysaccharide (LPS) mediates inflammation & septic shock
iv. Meningococcal infection => septicemia
Exotoxins (extracellular protein toxins)
i. Proteins secreted by many gram-positive & some gram-negative bacteria
ii. Many different exotoxins known to exist
iii. Direct effect on virulence
iv. May be responsible for entire symptoms of infection
v. Most toxic substances are known (1ug kills 103 guinea pigs)
vi. Possible target for neutralizing
antibodies Cholera
