COMPLEMENT SYSTEM
• Research on complement began in the 1890s, when Jules Bordet at the Institute Pasteur
in Paris showed that sheep antiserum to the bacterium Vibrio cholerae caused lysis of the
bacteria and that heating the antiserum destroyed it.
• He named those substances as Alexins.
• Paul Ehrlich coined the term complement.
• It is named "complement system" because it was first identified as a heat-labile
component of serum that "complemented or augment" antibodies in the killing of
bacteria.
• Consists of serum and cell surface proteins involved in defense against pathogens and
tissue damage mediated by antibodies.
• Plays major role in both innate and adaptive immunity.
• Complement system represents a group of about 30 proteins which augment or
complement the immune response.
• Most of these proteins are found in serum or on cell surface.
• Synthesized in liver as inactive precursors and are activated by proteolysis during their
interaction in a sequential manner.
• Also produced by blood monocytes, tissue macrophages and epithelial cells of he
gastrointestinal and genitourinary tract.
➢ GENERAL PROPERTIES
• Present in serum of all animals but its concentration is maximum in serum of guinea pig.
• Complement of one species are able to react with antibodies of other species but not to
the same extent.
• C-proteins constitute about 5% of normal serum protein
• Are glycoproteins.
• Are synthesized rapidly in inflammatory responses
• hence are called acute phase proteins.
• Heat labile and lost activity at 56° C for 30 mins and inactivated. Immunoglobulins are not
inactivated at this temperature.
• Binds with Fc potion of immunoglobulns.
➢ FUNCTIONS OF THE COMPLEMENT SYSTEM
• Cell Lysis
• Opsonisation
• Activation of Inflammatory response
• Clearance of immune complex
• Chemotaxis
, ➢ COMPONENTS OF COMPLEMENT SYSTEM
• Complement components are designated by numerals (C1–C9).
• Peptide fragments formed by activation of a component are denoted by small letters
resulting from cleavage of a component is designated “a” and the larger fragment
designated “b” (e.g., C3a, C3b)
• In the case of C2 larger fragment is designated as “a” and smaller fragment as “b”.
• larger fragments (b) - bind to the target near the site of activation
• smaller fragments (a) - diffuse from the site and can initiate localized inflammatory
responses by binding to specific receptors.
• The complement fragments interact with one another to form functional complexes.
➢ COMPLEMENT PATHWAY
Three pathway of complement activation is as follows:
1) classical pathway- it is an antibody dependent pathway and triggered by formation of
soluble antigen-antibody complex or by binding of the antibody to the antigen present
on the target cell surface.
2) Alternative pathway - antibody independent pathway stimulated by antigen directly
eg. Bacterial cell surface components
3) Lectin pathway- Also antibody independent but resembles classical pathway.
Three steps in this pathway are:
a) Activation
b) Amplification
c) Attack
Stages of complement activation:
Three main stages in the activation of complement by any pathway are:
• Formation of C3 convertase
• Formation C5 convertase
• Formation of membrane attack complex (MAC)
1) CLASSICAL PATHWAY
Activated by antigen-antibody complexes (immune complexes). The antibodies involved are
IgG or IgM bound to the surface of a pathogen.
Steps:
• C1 Complex Activation: C1q binds to the Fc region of antigen-bound IgG or IgM.
This activates C1r, which then activates C1s. C1s cleaves C4 into C4a (a weak anaphylatoxin)
and C4b, which binds to the pathogen surface. C1s also cleaves C2 into C2a and C2b. C4b and
C2a combine to form C3 convertase (C4b2a).
• Research on complement began in the 1890s, when Jules Bordet at the Institute Pasteur
in Paris showed that sheep antiserum to the bacterium Vibrio cholerae caused lysis of the
bacteria and that heating the antiserum destroyed it.
• He named those substances as Alexins.
• Paul Ehrlich coined the term complement.
• It is named "complement system" because it was first identified as a heat-labile
component of serum that "complemented or augment" antibodies in the killing of
bacteria.
• Consists of serum and cell surface proteins involved in defense against pathogens and
tissue damage mediated by antibodies.
• Plays major role in both innate and adaptive immunity.
• Complement system represents a group of about 30 proteins which augment or
complement the immune response.
• Most of these proteins are found in serum or on cell surface.
• Synthesized in liver as inactive precursors and are activated by proteolysis during their
interaction in a sequential manner.
• Also produced by blood monocytes, tissue macrophages and epithelial cells of he
gastrointestinal and genitourinary tract.
➢ GENERAL PROPERTIES
• Present in serum of all animals but its concentration is maximum in serum of guinea pig.
• Complement of one species are able to react with antibodies of other species but not to
the same extent.
• C-proteins constitute about 5% of normal serum protein
• Are glycoproteins.
• Are synthesized rapidly in inflammatory responses
• hence are called acute phase proteins.
• Heat labile and lost activity at 56° C for 30 mins and inactivated. Immunoglobulins are not
inactivated at this temperature.
• Binds with Fc potion of immunoglobulns.
➢ FUNCTIONS OF THE COMPLEMENT SYSTEM
• Cell Lysis
• Opsonisation
• Activation of Inflammatory response
• Clearance of immune complex
• Chemotaxis
, ➢ COMPONENTS OF COMPLEMENT SYSTEM
• Complement components are designated by numerals (C1–C9).
• Peptide fragments formed by activation of a component are denoted by small letters
resulting from cleavage of a component is designated “a” and the larger fragment
designated “b” (e.g., C3a, C3b)
• In the case of C2 larger fragment is designated as “a” and smaller fragment as “b”.
• larger fragments (b) - bind to the target near the site of activation
• smaller fragments (a) - diffuse from the site and can initiate localized inflammatory
responses by binding to specific receptors.
• The complement fragments interact with one another to form functional complexes.
➢ COMPLEMENT PATHWAY
Three pathway of complement activation is as follows:
1) classical pathway- it is an antibody dependent pathway and triggered by formation of
soluble antigen-antibody complex or by binding of the antibody to the antigen present
on the target cell surface.
2) Alternative pathway - antibody independent pathway stimulated by antigen directly
eg. Bacterial cell surface components
3) Lectin pathway- Also antibody independent but resembles classical pathway.
Three steps in this pathway are:
a) Activation
b) Amplification
c) Attack
Stages of complement activation:
Three main stages in the activation of complement by any pathway are:
• Formation of C3 convertase
• Formation C5 convertase
• Formation of membrane attack complex (MAC)
1) CLASSICAL PATHWAY
Activated by antigen-antibody complexes (immune complexes). The antibodies involved are
IgG or IgM bound to the surface of a pathogen.
Steps:
• C1 Complex Activation: C1q binds to the Fc region of antigen-bound IgG or IgM.
This activates C1r, which then activates C1s. C1s cleaves C4 into C4a (a weak anaphylatoxin)
and C4b, which binds to the pathogen surface. C1s also cleaves C2 into C2a and C2b. C4b and
C2a combine to form C3 convertase (C4b2a).
