Presented By: Yasir Mushtaq
Roll Number: 220096
Complement system refers to a group of (30) large
enzymatic proteins found in the serum and body fluids and it
completes the Antigen-Antibody reactions, lysis and
phagocytosis.
•It is represented by the letter C and numbered C1 to C9.
Other components of Complement system include B,D,P,H
and I.
 Discovered by Bordet in 1895 and named it as Alexin
 Term Complement was given by Paul Elrich in 1980
• Complement system is a part of immune system that enhances / complement's
the ability of antibodies and phagocytic cells to clear microbes and damaged
cells from the body.
• When there is an infection, this system of molecules is activated leading to the
sequence of events on the surface of pathogens. This helps to destroy the
pathogen and eliminate the infection.
• Complement components function in a cascade pattern, that is, a series of
reactions in which the preceding components act as enzymes on the succeeding
components. During complement activation, a complement component may be
cleaved into two dissimilar fragments. The larger fragment usually joins the
cascade, the smaller fragment usually possesses biological effects such a)
Defence mechanisms b) Causing smooth muscle contraction
• Synthesized in liver.
• Consists of a stalk & 3 sub-units -C1q, C1r & C1s. When
antibody binds to the antigen (pathogen), the AntigenAntibody complex is formed. The C1q subunit of C1 binds
to the Fc portion of antibody- This is called complement
fixation. This process activates C1q. The activated C1q
activates C1r which then activates C1s. C1s activates the
complements C4 & C2-in presence of Mg2+.
*The process of complement fixation is enhanced by Ca2+
ions
There are three Pathways the Complement System passes through
A. Classical pathway: The Classical pathway of the Complement system is one
of the three main activation pathways that form a crucial part of the immune
system. It is typically initiated by the binding of antibodies (IgG or IgM) to
antigens on the surface of pathogens, which triggers a series of following
reactions:
1. Antibody Recognition: Initiated by antibodies binding to pathogens.
2. C1 Complex Activation: Antibodies trigger the activation of the C1 complex.
3. Cleavage of C4 and C2: C1 complex cleaves C4 into C4a and C4b, and C2 into
C2a and C2b.
4. Formation of C3 Convertase: C4b and C2a combine to form C3 convertase
(C4b2a).
5. C3 Activation: C3 is cleaved into C3a and C3b by C3 convertase.
6. Amplification Cascade: C3b amplifies the response by recruiting more complement proteins.
7. Membrane Attack Complex: Leads to the formation of the membrane attack complex, causing
pathogen destruction.
B. Alternative Pathway: The Alternative pathway is one of the three pathways in the complement
system that plays a crucial role in the innate immune response. Unlike the Classical pathway, it does
not require the presence of antibodies.
1. Spontaneous Activation: Initiated without specific triggers.
2. C3 Binding: C3 continuously binds to pathogen surfaces.
3. Factor B Addition: Factor B joins C3 on pathogen surfaces.
4. Factor D Cleavage: Factor D cleaves Factor B, forming C3 convertase (C3bBb).
5. Cascade Amplification: C3bBb activates more C3 molecules, amplifying the response.
6. Membrane Attack Complex: Leads to the formation of the membrane attack complex, destroying
pathogens.
C. Lectin Pathway: The lectin pathway is one of the three pathways in the complement
system, which plays a crucial role in immune response. This pathway is activated by the
binding of mannose-binding lectin (MBL) or ficolins to carbohydrates on the surface of
pathogens.
1.
Recognition: MBL recognize and bind to specific sugar patterns on the surface of
pathogens, such as bacteria or viruses.
2.
Activation: Once bound to the pathogen, MBL interact with MBL-associated serine
proteases (MASPs), leading to the activation of these proteases.
3.
Cascade Activation: Activated MASPs then cleave complement proteins, including C4
and C2, initiating a cascade of reactions similar to the classical pathway.
4.
Formation of C3 Convertase: Cleavage of C4 and C2 results in the formation of the C3
convertase (C4b2a), which cleaves C3 into C3a and C3b.
5.
Amplification: C3b promotes the formation of C5 convertase (C4b2a3b), which
cleaves C5 into C5a and C5b.
6.
Membrane Attack Complex (MAC) Formation: C5b initiates the assembly of the
membrane attack complex (MAC), leading to the formation of a pore on the
pathogen's membrane, causing cell lysis.
Overall, the lectin pathway enhances the immune response by recognizing and targeting
pathogens through the activation of the complement system.