Dr.

Ashish Kumar Singh

Complement System

Dr. Ashish Kumar Singh

1
 Complement

 What is it? A series of serum protein

 How is it recognized? By its ability to mediate

cell lysis.

 What does it have to Complement has three

do with immunology? function:
1. Opsonin
2. Chemo-attractant
3. Membrane attack
Dr. Ashish Kumar Singh complex (MAC) 2
 Complement
 Discovered by Jules Bordet as
 Hat-labile component of normal plasma
 Complement causes
 The opsonisation and
 killing of bacteria
 The complement system refers to a series of
>20 proteins, circulating in the blood and
tissue fluids.
 Made by liver
 It assist a complements the immune cell in
destroying pathogens.

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 Activation Complement System
 Most of the proteins are Proteolytic enzymes

 In absence of infection they circulate in

inactive forms.

 Complement system get activated in response

to the recognition of molecular components of
microorganisms they become sequentially
activated in an enzyme cascade

 When in-active complement protein become

active then it leads to complement activation
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 Activation mechanism
 The activation of one protein enzymatically
cleaves and activates the next protein in the
cascade.
Inactive Active
protein

Active
Inactive
Active
Inactive

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  Complement pathways are initiated by proteins that
binds to pathogens.
 Either directly or
 via an antibody or
 pathogen specific protein

 After a conformational change

 Enzymatic mediators activate other enzymes that

generate the central proteins of the complement
cascade

 C3 and C5 convertases which Cleave C3 and C5.

 Releasing active components that mediate all

function of complement. 6
Dr. Ashish Kumar Singh
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  Cytolysis:
 Cell + anti-cell antibody (Ab) + Complement
(C) may result in lysis of the cell.

 Cytolysis is the dissolution of a cell.

 When an RBC is lysed by the cytolysis is
called haemolysis.
 When bacterial cell is lyse, the lysis is called
bacteriolysis.

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  Opsonization:
 Antigenic particle + antibody (Ab) +
Complement (C) enhances phagocytosis by
monocytes (Mo); macrophages (MØ);
polymorphonuclear cells (PMNs)

 Opsonization is a process by which antibodies

bind to a pathogen and the pathogen is marked
for killing by phagocytes.
 The marking substance is called Opsonin.

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 Complement can be activated
via three different pathways

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 Nomenclature
 The enzyme of the classical pathway were
identified first
 Designated the letter “C” followed by a
number
 C1,C2, C3, C4, C5, C6, C7, C8, C9

 When a protein is broken down into two,

 The resulting peptide fragment are
designated by a lowercase suffix “a”, “b”.
 Suffix “a” represent smaller fragment.

 Suffix “b” represent larger fragment.

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 Nomenclature
 In general:
 Larger fragment contribute in enzymatic
activity

 Suffix “a” represent smaller fragment.

 Suffix “b” represent larger fragment.

 C2 is an exception
 C2a (larger fragment)
 C2b (smaller fragment)

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 Nomenclature
 C1 protein
 C1 is complex protein
 Large subunit C1q,
 Two proteases C1r and C1s

 Protein of alternative pathways are termed

as factors
 They are designated by capital letter
 Example Factor B, Factor D

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 Alternative pathway
 Discovered in second

 One of the first response of the innate immune

response.

 C3 protein is the most abundant protein of

complement system present in blood.

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 Alternative pathway
 Hydrolysis of C3 in blood
 C3 hydrolysis forms C3(H2O)
 Induces conformational change for binding of
other factor
 Factor B binds to C3(H2O)
 Factor D cleaves the factor B.
 Larger fragment of factor B remain bound to
C3(H2O) and form a complex C3(H2O)Bb.
 C3(H2O)Bb have protease activity called as C3
convertase.
 It cleave C3 in C3a and C3b.
 It is in soluble C3 convertase.
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 Alternative pathway
 C3b becomes firmly fix to pathogen
(complement fixation)

 Factor B binds with C3b on the surface of

pathogen form C3bB complex

 Factor D cleaves Factor B generates C3bBb

complex which located on microbial surface.

 C3bBb also known as alternative C3 convertase.

 Properdin stabilizes the C3bBb complex.
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 Properdin stabilizes the
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C3bBb complex 18
 Lectin pathway
 Lectins are soluble proteins
 Mainly produced by liver
 Recognize specific carbohydrate components
present on microbial surface.

 Mannose binding lectin (MBL) first lectin to be

discovered.

 MBL binds to mannose-contanning

carbohydrates of bacteria , fungi & viruses.

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 MBL (Mannose binding lectin)
 MBL circulates in plasma as a complex with two
proteases which are MASP-1 and MASP-2

 MBL associated Serine proteases (MASP)

 MBL complex binds to the surface of pathogen

 Triggers lectin pathway

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 Lectin pathway

 MASP-2 acts a convertase

 Cleaves C4 in C4 a and C4b

 C4b bind to the microbial surface

 C2 interact with MASP-2 and cleaved in C2a

(larger fragment) and C2b (smaller fragment).

 C2a binds with pathogen bound C4b and form

a Complex C4bC2a (C3 convertase)
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 Classical Pathway
 First discovered
 Activation of this pathway depends on
antibodies
 C1 play important role in activation of classical
pathway.
 C1 protein is complex
 C1r &C1s (acts as protease)

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 Classical Pathway
 C1 complex binds to the Fc region of antigen-
bound Antibodies.
 Proteases cleaves C4 in C4a and C4b
 C4b bind to the microbial surface
 C2 interact with protease and cleaved in C2a
(larger fragment) and C2b (smaller fragment).
 C2a binds with pathogen bound C4b and form a
Complex C4bC2a (C3 convertase)

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 C5 Initiates the Generation of the
MAC (Membrane attack complex)

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 THANK YOU

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