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The Complement System
The Complement System
The Complement System
BARRIERS.
OUTLINE:
Mechanism of action
COMPLEMENT SYSTEM:
HISTORICAL OVERVIEW: In the late 19th century, blood serum was found to contain a
"factor" or "principle" capable of killing bacteria. In 1896, Jules Bordet, a young Belgian
scientist in Paris at the Pasteur Institute, demonstrated that this principle could be analyzed into
two components: a heat-stable and a heat-labile component. (Heat-labile means that the
component loses its effectiveness if the serum is heated.) The heat-stable component was found
to confer immunity against specific microorganisms, whereas the heat-labile component was
found to be responsible for the non-specific antimicrobial activity conferred by all normal serum.
This heat-labile component is what we now call "complement."
The term "complement" was introduced by Paul Ehrlich in the late 1890s, as part of his larger
theory of the immune system. According to this theory, the immune system consists of cells that
have specific receptors on their surface to recognize antigens. Upon immunization with an
antigen, more of these receptors are formed, and they are then shed from the cells to circulate in
the blood. These receptors, which we now call "antibodies," were called by Ehrlich
"amboceptors" to emphasize their bifunctional binding capacity: They recognize and bind to a
specific antigen, but they also recognize and bind to the heat-labile antimicrobial component of
fresh serum. Ehrlich, therefore, named this heat-labile component "complement," because it is
something in the blood that "complements" the cells of the immune system
The rational for the inclusion of complements in the innate immune response is that:
i. It is not adaptable
ii. It does not change over the course of ones lifetime.
i. Hepatocytes
ii. Macrophages
iii. Gut epithelial cells
The rest are kind of regulatory proteins. The protein components in the
complement system are all soluble proteins.
C5 to C9 ATTACK
Another way of classification employs the time phase of the whole process.
Hence we have the EARLY PHASE, THE INTERMEDIATE PHASE & LATE PHASE.
Larger fragments bind tightly to the target cell membrane by its newly
exposed membrane binding site and helps to carry out the next reaction in
the sequence. In this way complement activation is confined largely to the
cell surface where it begun.
Factor D which circulates in the blood in an active form cleaves the bound
factor B to generate the active fragment Bb and therefore produce C3bBb
(which is the C3 convertase for the alternative pathway) and therefore
generates more C3b molecules some of which binds C5. The C3 convertase
can also act as a C5 convertase and cleave the membrane bound C5
molecules to initiate the assembly of the Membrane Attack Complex which is
involves the C5b bound to the C3b binding to the C6 to form C56 and then
C7 to form C567. The C567 complex then binds firmly via the C7 to the
membrane. This complex adds one molecule of C8 to form C5678 which then
binds 8 to 18 molecules of C9 which partially unfold and polymerise into a
transmembrane channel.
References
Molecular Biology of the Cell, 2nd Edition, Bruce Alberts, Dennis Bray, Julius Lewis et al,
Published by Garland Publishers 1999, Page 1032-1033
Human Physiology, 5th Edition, S I Fox, Published by McGraw Hill Companies Inc, 1996
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