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0:05
I'd like to briefly review
the complement pathway.
It's so important
for understanding
the pathogenesis of
Streptococcus pyogenes
and actually quite a few
other bacterial pathogens.
In a non-immune animal,
the alternative pathway
is critical for providing
effector molecules that
remove bacteria from tissue.
In an immune animal, the
classical pathway is
activated by
antibody-antigen reactions.
There are several important
molecules generated by
the proteolytic cleavage of
complement proteins
in our blood.
One of the most
important is C3b.
It's an opsonin.
It butters up bacteria so
they can be recognized by
complement receptors
on phagocytic cells.
C5a is the chemotaxin
that attracts
phagocytes such as PMNs or
macrophages very early
in an infection.
Obviously, both of
these molecules are
critical for removing
bacteria from tissues.
If the bacterium is a
gram-negative bacterium,
the complement system
ultimately produces
a complex called the
membrane attack complex.
This inserts holes in
the outer membrane of
gram-negative bacteria.
The membrane attack complex has
really no effect on
gram-positive bacteria,
which lack an outer membrane.
1:32
As I stated, C5a is
an important product of
the complement activation.
It's the earliest
signal to attract
phagocytic cells to
a site of infection.
IL8 is another chemotaxin
that's important.
It's produced somewhat
later by inflammation.
Both chemotaxins recruit
PMNs and macrophages locally
to clean up foreign microbes
before infection progresses.
The C5a peptidase
or SCPA is produced
by all M types of S. Pyogenes
and human isolates of
Streptococcus agalactiae,
group C streptococci, and
group G streptococci.
Cow, pig, and horse isolates
genetically lack the protease.
S. Pneumoniae also produces
a related but
different protease.
Strep also produces
an IL8-specific
protease called SpyCEP.
It's not produced by all
M types of S. Pyogenes.
Both proteins are
highly conserved,
and both are candidates
for vaccine development.
The reference listed on
the slide by McKenna is
an in-depth review
of the biochemistry
and the role of these
proteases in infection.
