description of complement system

1. COMPLEMENT
Dr Amit kumar

2. 1) General properties
 Nonspecific protein : in human and animal serum
 Denoted by ‘C’( C1-C9)
 Activated : by Antigen and antibody reaction
 Constitute : about 5% total serum protein and level donot increase either
vaccination or infection
 Bind with Fc portion of Ab (c/d fixing or consumption)
 Donot combine with free Ag or Ab (only withAg Ab complex) except IgM ,IgG 1,
IgG2 , IgG3 can fix complement ( as presence of c binding site of Fc portion)
 heat labile : inactivate at 56 o c for 30 minutes

3. A

4. B) COMPONENTS OF COMPLEMENT
 9 components : C1-C9
C1 has 3 subunits: C1q , C1r , C1s
C3 in serum : highest concentration
(1.2mg/ml)
C2 in serum : lowest concentration
(0.015mg/ml)

5. c) Synthesis
Liver is major
site of synthesis
of complement
protein
Blood monocytes
Epithelial cell
Macrophage
Blood monocytes , tissue macrophages , and epithelial cells of GIT and
genitourinary tract are minor sites

6. D) Complement activation
 Complement have two equal fragments :
 Larger fragment ‘b’ and smaller fragment ‘a’ an
exception C2a is larger fragment.
 During proteolysis : smaller fragment removed and
larger fragment participated in cascade reaction
 Cascade reaction: After formation of complex by
interacting with molecules ,The fragment of complement
act as enzymatic like activity

7. 2) Complement pathway
 a) classical pathway : Antibody dependent
pathway, triggered by antigen antibody
pathway
 b) Alternative pathway : Antibody
independent pathway, triggered by antigen
directly.
c) Lactin pathway : Antibody independent
pathway

8. a) Classical pathway
 Complement activity of immune cytolysis is described as lysis of erythrocyte
sensitized by its antibody .
 Erythrocyte (E) – Antibody (A) known as EA complex when complement attached ,
it is called as EAC
 Immune cytolysis is initiated by binding of C1 to EA
 C1q is recognition unit of C1 , in the presence of calcium ions C1q reacts
with FC portion of bounded antibody molecules ( IgM or IgG) in EA .
 Activated C1q activates C1r and C1s .

9.  C1s act as esterase which splitsC4 into C4a and
C4b, then larger fragment (C4b) binds with C1 to
form EAC14b and participate in complement
cascade reaction
 EAC14b in the presence of magnesium ions split
C2 into C2a and C2b , larger fragment 2a bind
with EAC14b to form C14b2a ( act as C3
convertase)

 C3 convertase splitsC3 and larger fragment of C3
binds (C3b)with C14b2a (C3 convertase) to form
C14b2a3b (act as C5 convertase)
 C14b2a3b (act as C5 convertase) splitsC5 and
larger fragment of C5 binds (C5b)with C14b2a3b
(C5 convertase) to form C14b2a3b5b.
 C6 and C7 join with C5b to form C567 and bind
with cell membrane and prepare for cell lysis by
C8 and C9.
C1:
c1q,c1
r and
c1s

10. b) Alternative pathway
 Initiated with activation of C3 , unlike classical
pathway donot require C3 convertase to actvate
C3 component of complement.
 C3 component activated by bacterial endotoxin,
yeast cells , IgA & D , the cobra venom factor and
nephoritic factor (a protein in serum of
glomeruonephritis patient).


11.  Binding of C3b with an activator in the presence
of magnesium ions.
 C3b present in circulation but in free state
rapidly inactivated by serum protein factor H & I
 BoundC3b , in the presence of magnesium ions
interact with plasma protein factor B to form
C3bB
 factor B portion of C3bB complex is split by
factor D into Ba and Bb
 Larger fragment Bb binds with C3bB to form
C3bBb
 C3bBb act as a C3 convertase and split C3 into
C3a and C3b.
 Then larger fragment C3b paticipates in
complement reaction (cascade reaction) and
bindsC3bBb to form C3bBb3b.
 Remaining reaction is same as classical pathway
C3
C3a C3b
Anaphylactic
C3bBb3b (C5
CONVERTASE)
C5
C5a
Anaphylactic
Mg ++
Bb

12. MBL + mannose residues on microbial
surface
MBL/MASP COMPLEX
C4
C4a
C4b
MBL/MASP4b
C2
C2a
C2b
MBL/MASP4bc2a
C3 convertase
c3
C3a
C3b
MBL/MASP4bc2ac3b
(C5 convertase)
C5
C5a
C5b
•Mediated by lectin protein on host interact with
mannose residues (present on microbial surface)
•Involves all component of classical pathway except
C1 .
• INITIATION OF PATHWAY
i) MANNOSE BINDING LECTIN ( SPECISIC HOST
PROTEIN) bind with mannose residues (present
on microbial surface)
ii)Another specific HOST PROTEIN MASP (MBL
associated serine protease) get complex with MBL
forming MBL/MASP complex
iii) MBL/MASP complex claves C4 and C2 then
larger fragment of each component binds to
MBL/MASP to form MBL/MASP4b ,
MBL/MASP4b2a respectively
iv) Reaming stage similar to the classical pathway
C) Lectin pathway

13. Overview of pathway of complement

14. 3) Function of complement
 i)Target cell lysis by MAC (MEMBRANE ATTACK COMPLEX):
MAC makes pores in target cells membrane that allow passage of
various water and ions into the cells leading to cell swelling , lysis
and death.
 ii) Amplification of inflammatory response : C3a, C4a and C5a are
anaphylatoxin by degranulation of mast cells to release Histamine
and others mediators and cause increase vascular permeability and
chemotactic.
 iii) Hypersensitivity reaction : participate in type-2(cytotoxic: –
incompitable transfusion and therombocytemia) and type -3
reaction (immune complex :-serum sikness and arthus reaction)

15.  iv) Opsonisation: C3b and C4b induce
phagocytosis as phagocytic cells posses receptor
for C3b and C4b. Once complement activated C3b
and C4b bind with phagocytic cells and induce
phagocytosis.
 v) Autoimmunity : serum complement level
decrease in many autoimmune disease ( systemic
lupus erythematous and rheumatoid arthritis)

16. vi)
vii)

17. 4)

20. 5)

21. 6) COMPLEMENT DEFICIENCY
DISEASE

22. QUESTIONS
 1) classical pathway
 2) lectin pathway
 3) alternative pathway
 4) complement deficiency
 5) complement regulation
 6) what is complement ? Discuss briefly its
importance in various type of hypersensitivity
reactions.

23. Multiple choice questions
 1)Which of the following best denotes
classical complement pathway activation in
immunoinflammatory condition.
A) C2 , C4 , C3 DECREASED
B) C2 AND C4 NORMALAND , C3 IS
DECREASED
C) C3 NORMALAND C2 C4 DECREASED
D) C2, C4,C3 ALL ARE ELEVATED

24.  2) C3 convertase act as
 A) c4b2b
 B) c4b2B3a
 C) c4b
 D) c3

25.  3) which complement component is involved
in both classical and alternative pathways.
 A) C1
 B) C2
 C) C3
 4) C4

26.  4) Chemoattractant is
 A) C5a
 B) c1
 C) c3
 D) c2

27.  5) complement necessary for neisseria
infection is/are .
 A) C5
 B) C6
 C) C7
 D) C8
 E) C9

28.  6) COMPLEMENT C5-C9 PREDISPOSINGTO
WHICH INFECTION .
 A) meningococci
 B) pneumococci
 C) pseudomonas
 D) all

29.  7) recurrent facial /oropharyngeal/laryngeal
edema in a patient has low c4, normal c3 and
normal factor B.The pathogennesis is most
likely due to.
 A) immune complex disease
 B) c1 esterase inhibitory deficiency
 C) hereditary disease of c2