There are two disparate routes through which the immune
system can exert its effect. The more readily
understood strategy is referred to as resistance in which the immune system is mobilized
to detect the offending pathogen and eliminate it. There is, however, another route that the
immune system can take and that is tolerance in which the immune system adapts
to a certain level of tissue damage inflicted by the offending organism. Interestingly enough, the deleterious impact
of infectious disease can be the result of either failed resistance or failed
tolerance.
Usually, a deadly outcome of a microbial infection is
relegated to either high virulence or decidedly poor resistance on the part of the
host immune system. However, there is another
possible explanation. The damage
produced by an invading pathogen can be directly related to the toxins it
produces, or to the inflammatory response precipitated by the immune system
that can lead to tissue damage. This
latter effect is referred to as “extrinsic virulence.” Insufficient tissue protection and subsequent
repair of damaged tissue can also contribute to the lethality of the infectious
process.
Dr. Amanda Jamieson and her colleagues at the Howard Hughes
Medical Institute and Department of Immunobiology at the Yale University School
of Medicine chose to study the co-infection of the influenza virus with
Legionella pneumophila using a mouse model as a way of determining whether it
is resistance or tolerance on the part of the host immune system that
determines lethality.
Through their detailed studies, they found that
susceptibility to co-infection occurred even when the bacterial infection was
controlled by the immune system. From
this, they were able to conclude that the failure of host defenses was directly
related to a diminished capacity to tolerate tissue damage.
This is a very interesting finding that may have practical
implications regarding the clinical approach to patients whose health is
seriously impacted by co-infection.
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