Understanding the Complement System
Translated by
ScribdTranslationsUnderstanding the Complement System
Translated by
ScribdTranslationsThe complement system belongs to innate immunity and is composed of a
series of enzymes, proteins, and receptors that perform the function of regulating processes
inflammatory, removal of altered and damaged cells, signaling the presence of pathogens and
regulates the response of adaptive immunity. The complement system is also
involved in the elimination of immune complexes, mobilization of stem cells, regeneration
tissue and lipid metabolism.
Complement system proteins are constantly in an inactive state in the
circulation, and when necessary they are activated gradually, and this occurs through
pathways that stimulate the binding of some molecules of the system to invading pathogens
of the organism, which end up triggering the cellular lysis of the microorganism. The animals
healthy, that is, absent of pathogens, the complement system remains inactive, and is only
activated by molecular patterns associated with the pathogen (PAMPs) found in
superficial infectious agent, and also through the binding of the antigen-antibody complex.
To start the action of the complement system, it needs to be activated through
one of its three mechanisms called the pathway, the alternative pathway (PAMPs), Lectin (PAMPs)
the classic (antigen + antibody), and then generate a key protein
in the C3b called system, to then promote the formation of the terminal complex that will remain
origin to MAC (membrane attack complex)
The classical route begins with fragment C1, which is the most complex fragment.
formed by a set of molecules consisting of 6 molecules of C1q, 2 molecules of C1s and
2 molecules of C1r.
This pathway initially requires the interaction between antibody and antigen, where
the main immunoglobulins involved are IgM and IgG, as they are the first to be
synthesized at the beginning of an immune response (mainly IgM).
When the IgMs identify a pathogen, they bind to the membrane cells.
of the antigen, and then C1 binds to the constant fraction of antibodies through its C1q fraction, and
So the fractions C1q and C1s are activated to carry out the cleavage of the proteins.
The proteins of the complement system are present in plasma, and upon entering
In contact with C1 are cleaved. The first to be cleaved are the proteins C2.
fragment C2aeC2be a protein C4em fragment C4aeC4b. Generally the fragments
I am going to plug in the blood current, and the fragments will be from the pathogen membrane.
to proceed with the reactions, however in this first cleavage the fragments that return to
blood currents are the fragments of the membrane
together, forming aC3convertase.
AC3 convertase converts protein C3 into fragment C3b, where C3b is
adhere to C4b2a forming the enzyme C5 convertase (C4b + C2a + C3b), and the fragment C3a
returns the blood flow and acts like aflatoxin attracting defense cells to the
local where the pathogen is, mainly mast cells and basophils that perform the
histamine synthesis causing vasodilation and favoring diapedesis. AC5
convert C5 protein into fragment C5a and C5b, where it returns to the current
blood where it acts as an anaflotoxin performing chemotaxis and attaches to
pathogen membrane, but separated C5 convertase. The C5b protein performs the attraction.
the other proteins, namely C6, C7, C8 and several fragments of C9, which in the end that
They form the MAC (Membrane Attack Complex), initiating the osmotic lysis of the pathogen.
O MAC age como poros na membrana do patógeno, favorecendo a entrada de água na
agent cell, until cell lysis occurs.
Unlike the classical pathway, its activation occurs through the recognition of
PAMPs. The key protein C3 present in circulation is physiologically cleaved into C3a and
C3b, and when there is no presence of pathogen, it is hydrolyzed because it is not needed.
used, however when the presence of a pathogen occurs in the bloodstream another
complement system molecule called factor B adheres to the agent's membrane, and
when the fragmentC3 recognizes the factor Bligado to the pathogen, it adheres to it. After the
the factor is the fragment C3b that binds, the factor enters into action on factor B, carrying out the
cleavage of this emBBeBb, and then the factorBB is disregarded for the plasma and the factorBb
remains on the pathogen membrane with aC3b. The factor Bb + C3b perform the cleavage
from another protein C3, in C3 becomes C3a, where factor C3b also adheres to the membrane
the pathogen forming C3b+Bb+C3b which is nothing more than the C5 convertase, and the
the sequence is the same as the classic way until the formation of the MAC.
This pathway is very similar to the classical pathway, but it is initiated by a molecule.
of soluble pattern recognition that identifies microbial carbohydrates. The
molecules that activate the pathway are mannose-binding lectin (MBL) and ficolin, which
they are linked to a carbohydrate called mannose, found in the cell wall of the pathogen
(PAMP). After the MBL binds to the pathogen membrane, it activates a
serum protease called MASP-2, which cleaves the C4 protein into fragments
C4a and C4b, where the fragment C4a binds to the pathogen membrane, and then to
protein C2 is also cleaved into C2a and C2b, and the C2b fragment binds to the C4b fragment
on the pathogen membrane, following the pathway like the others, until the formation of the MAC.