Alternative

complement
pathway

The alternative pathway is a type of

cascade reaction of the complement
system and is a component of the innate
immune system, a natural defense against
infections.
 The classical and alternative complement
pathways.

Alternative pathway. (Some labels are in

Polish.)

The alternative pathway is one of three

complement pathways that opsonize and
kill pathogens. The pathway is triggered
when the C3b protein directly binds a
microbe. It can also be triggered by foreign
materials and damaged tissues.
Cascade

This change in shape allows the binding of

plasma protein Factor B, which allows
Factor D to cleave Factor B into Ba and Bb.

Bb remains bound to C3(H2O) to form

C3(H2O)Bb. This complex is also known as
a fluid-phase C3-convertase. This
convertase, the alternative pathway C3-
convertase, although only produced in
small amounts, can cleave multiple C3
proteins into C3a and C3b. The complex is
believed to be unstable until it binds
properdin, a serum protein. The addition of
properdin forms the complex C3bBbP, a
stable compound which can bind an
additional C3b to form alternative pathway
C5-convertase.

The C5-convertase of the alternative

pathway consists of (C3b)2BbP
(sometimes referred to as C3b2Bb). After
the creation of C5 convertase (either as
(C3b)2BbP or C4b2b3b from the classical
pathway), the complement system follows
the same path regardless of the means of
activation (alternative, classical, or lectin).
C5-convertase cleaves C5 into C5a and
C5b. C5b binds sequentially to C6, C7, C8
and then to multiple molecules of C9 to
form membrane attack complex.
Regulation

Since C3b is free and abundant in the

plasma, it can bind to either a host cell or a
pathogen surface. To prevent complement
activation from proceeding on the host
cell, there are several different kinds of
regulatory proteins that disrupt the
complement activation process:

Complement Receptor 1 (CR1 or CD35)

and DAF (decay accelerating factor also
known as CD55) compete with Factor B
in binding with C3b on the cell surface
and can even remove Bb from an
already formed C3bBb complex
The formation of a C3 convertase can
also be prevented when a plasma
protease called complement factor I
cleaves C3b into its inactive form, iC3b.
Factor I requires a C3b-binding protein
cofactor such as complement factor H,
CR1, or membrane cofactor of
proteolysis (MCP or CD46)
Complement factor H can inhibit the
formation of the C3 convertase by
competing with factor B for binding to
C3b;[1] accelerate the decay of the C3
convertase;[2] and act as a cofactor for
factor I-mediated cleavage of C3b.[3]
Complement factor H preferentially
 binds to vertebrate cells (because of
affinity for sialic acid residues), allowing
preferential protection of host (as
opposed to bacterial) cells from
complement-mediated damage.
CFHR5 (Complement factor H-Related
protein 5) is able to bind to act as a
cofactor for factor I, has decay
accelerating activity and is able to bind
preferentially to C3b at host surfaces.[4]

Role in disease

Dysregulation of the complement system

has been implicated in several diseases
and pathologies, including atypical
hemolytic uremic syndrome in which
kidney function is compromised. Age
related macular degeneration (AMD) is
now believed to be caused, at least in part,
by complement overactivation in retinal
tissues.[5] Alternative pathway activation
also plays a significant role in
complement-mediated renal disorders
such as atypical hemolytic uremic
syndrome, C3 glomerulopathy, and C3
glomerulonephritis (Dense Deposit
Disease or MPGN Type II).[5]

See also

Classical complement pathway