Resistance and Tolerance Flashcards
Describe the evidence that gave rise to the concepts of resistance and tolerance.
Some drosophila mutants showed increased lifespan when infected with mycobacterium marinum. However, the mutants didn’t have decreased bacterial number and therefore did not have an increased ability to clear the infection. The mutants were exhibiting a tolerance effect.
What two properties change over time during an infection?
Microbe numbers and host health.
Describe the changes to host health during infection.
Progressive decline in health until the pathogen is cleared, when normal health is restored.
Define resistance.
The ability of the host organism to resist infection and to fight infection of a specific pathogen. Defined in terms of microbial numbers per host.
Define tolerance.
The ability of the host organism to reduce the damage caused by a specific pathogen. Differences in pathology occur between hosts, and host have different abilities to survive an infection.
Why is it important to understand tolerance mechanisms?
If tolerance could be increased, it could give patients a better chance of surviving an infection when given the standard treatments.
What does tolerance depend on?
Inhibition of pathology during innate immunity.
Why is resistance indispensable?
A host must be able to kill invading pathogens in order to survive.
What is the most prominent source of pathology during an infection?
The host’s immune response.
What else does tolerance depend on?
Individual variation in resistance due to allelic diversity.
How does ferritin promote tolerance to sepsis?
Binds free haem released by lysed RBCs, meaning free haem cannot trigger damage signalling via TLR4 and glucose-6-phosphatase expression is not switched off, maintaining gluconeogenesis. Ferritin binding of free haem also reduces pathology through prevention of hydroxyl radical formation.
How does the SlrP effector molecule promote tolerance to Salmonella infection?
SlrP (injected into cells by salmonella through T3SS), inhibits formation of the inflammasome. Caspase-1 is not activated, and pro-IL-1B is not cleaved. IL-1B cannot signal via the vagus nerve to stimulate anorexia. Mice eat more, increasing fecal shedding, promoting host survival and pathogen transmission between hosts.
