Since the complement system involves the formation of many biologically active substances, there are many regulatory systems to prevent unwarranted damage to the human host.
Regulation of Complement System
Since the complement system involves the formation of many
biologically active substances, there are many regulatory systems to prevent
unwarranted damage to the human host. The activities of the different complement
components activated at each stage of the cascade are regulated by several mechanisms. The following are regulators of the complement system:
1. Level of
antibody: The level of antibody itself is the firstregulatory step in the
classical pathway. If antigen is not bound to the antibodies, the
complement-binding sites on the heavy chains of IgG and IgM are unavailable to
the C1 component of the complement. This means that complement is not acti-vated
even if IgM and IgG are present in the blood at all times. However, when
antigen binds with specific antibodies, a con-formational shift occurs and that
allows the C1 component to bind and initiate the cascade reaction.
C1 inhibitors: These inhibitors play a
critical role inlimiting unnecessary complement activation. These prevent the
formation and function of C1qrs complex by causing C1s to dissociate from
C1qrs. The C1 inhibitors may also aid in the removal of the entire C1 complex
from the antigen–antibody complexes.
Other inhibitory substances: Multiple substances
haveinhibitory effects over different steps of the activation sequence of the
classical pathway. These are considered to be host cell protective mechanisms.
These mechanisms probably help to protect the host cells from the possible
bystander damage initi-ated by activated complement fragments (C3b and C4b)
being formed on and near its surface.
(DAF): It is another inhibitorysubstance located in a large variety of
host cell membranes. It is so termed because it can accelerate the dissociation
of active C4b2a complexes, turning off their ability to activate native C3. In
addition, DAF remains attached to membrane-bound C4b and C3b, and prevents the
subsequent interac-tion with C2a and factor B, respectively. As a consequence,
the two types of C3 convertases, C4b2a and C3bBb, are not formed; hence, the
rate of C3 breakdown is reduced and the host cells are spared from
complement-mediated membrane damage.
Regulation of alternative
pathway: The alternative path-way has its own set of regulatory proteins and
mechanisms. It is mediated by the binding of factor H to C3b and cleavage of
this complex-by specific plasma inhibitor factor I, a protease. This reduces
the amount of C5 convertase available.
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Microbiology and Immunology: Complement System : Regulation of Complement System |