COMPLEMENT SYSTEM
-Consists of a group of soluble proteins, which are
proteases that cleave and activate one another in a
sequential manner. The complement system is a crucial
part of the innate immune system, comprising a group
of proteins that work together to defend the body
against pathogens, clear immune complexes, and
contribute to the inflammatory response
THERE ARE THREE MAIN EFFECTS OF
ACTIVATION OF THE COMPLEMENT SYSTEM
Lysis of cells
Generation of inflammatory
mediators
Opsonization leading to
enhanced phagocytosis.
THERE ARE 3 COMPLEMENT PATHWAYS
THAT MAKE UP THE COMPLEMENT SYSTEM
The Alternative or Properdin
Complement Pathway.
The Classical Complement
Pathway
The Mannose-Binding Lectin or
MBL Pathway
THE CLASSICAL PATHWAY
- is primarily triggered by the binding of specific
antibodies to antigenic targets on the surface of
pathogens or other foreign cells. Also it begins with a
protein complex called C1.
-C1 is made up of three distinct subunits. The C1q, C1r
and C1s
THE LECTIN PATHWAY
-is activated by specific patterns of sugars found on
the bacterial cell wall. Lectin, the first to be
discovered, is a pattern recognition receptor that
recognizes the pattern of mannose-containing sugars.
-is activated by the interaction of microbial
carbohydrates (lectins) with mannose-binding lectin
(MBL) or ficolins found in the plasma and tissue fluids.
Mannose-binding lectin (MBL) - also known as mannose-
binding protein or MBP. MBL is a soluble pattern-
recognition receptor that binds to various microbial
carbohydrates such as those rich in mannose or fucose,
and to N-acetylglucosamine. These glycans are common
in microbial glycoproteins and glycolipids but rare in those
of humans. MBL is synthesized by the liver and released
into the bloodstream as part of the acute phase response
that will be discussed later in this unit. The MBL is
equivalent to C1q in the classical complement pathway.
Both mannose-binding lectin (MBL) and ficolin form
complexes with MBL-associated serine proteases called
MASP1 and MASP2, which are equivalent to C1r and C1s of
the classical pathway.
THE ALTERNATIVE PATHWAY
-is activated by bacterial products such as endotoxin
or complexes of immunoglobulins. It is part of innate
immunity and the first to be activated on initial
exposure to the antigen.
-the alternative complement pathway is mediated by
C3b, produced either by the classical or lectin
pathways or from C3 hydrolysis by water.
It should be noted that all three
pathways lead to the production of C3b,
called the central molecule of the
complement system. C3b functions as
an opsonin. At the same time, B cells
have a receptor for C3b and binding of
C3b to the receptor on the B cells will
stimulate differentiation of B cells into
antibody-producing plasma cells,
promoting further production of
antibodies. In addition to C3b, C1q in
the classical pathway also functions as
an opsonin.
Other important products of complement
activation include the following:
1. C3a and C5a - chemotactic for neutrophils; chemical mediators in
inflammation causing vascular leakage or increased vascular
permeability.
2. C3a, C4a, and Ca - function as anaphylatoxins, causing
degranulation of mast cells and release of histamine; Ca is the most
potent, followed by C3a then C4a.
3. Membrane attack complex (MAC) - cause lysis of the bacterial
cell.
