Immunology is the study of the immune system and is a very important branch of the medical and biological sciences. The immune system protects us from infection through

1. Lecture
5

2. Learning Objectives
•After reading and studying this chapter, you should be
able to:
♦ Describe sequence of events when the classical pathway
and the alternative pathway of the complement system is
activated.
♦ Discuss biological effects of complement.
♦ Describe complement deficiencies and associated
diseases.

3. Complement System
•Complement: The term ‘complement’ (C) refers to a
system of factors which occur in normal serum and are
activated characteristically by antigen-antibody
interaction and subsequently (next) mediate a number of
biologically significant consequences.
•The complement is so named because this proteins assist
or complement the immune cells to destroy the pathogen.

4. Conti……….
•The complement system is an alarm and a weapon against
infection, especially bacterial infection.
•The complement system includes serum and membrane-
bound proteins that function in both acquired and
constitutive (natural) host defence system.
•These proteins are highly regulated and interact via a series
of proteolytic cascades.

5. Conti…………..
•The complement system belongs to the group of
biological effectors mechanisms (called triggered
enzyme cascades) which also includes coagulation,
fibrinolytic and kinin systems. Such biological cascades
have distinct advantages.
• For example, each enzyme in the cascade is able to
activate many molecules of the succeeding component
providing for amplification of the response at each step.

6. Conti………
•Every step has its own control mechanisms so that, the
cascade can be regulated with precision.
•A cascade: is a set of reactions that amplify (increase)
some effects, i.e. more products are formed in the second
reaction than the first, still more in the third and so on.

7. General Properties of
Complement
•1. Present in the sera of all mammals and of most
lower animals:
•Complement is present in the sera of all mammals and
also in that of most lower animals, including birds,
amphibians and fishes.
Hepatocytes, blood monocytes, epithelial cells of the
gastrointestinal tract, and tissue macrophages
synthesize complement proteins.

8. Conti…………
•2. Nonspecific serological reagent: It is a nonspecific
serological reagent in that complement from one species
can react with antibodies from other species, though the
efficiency of reaction is influenced by the taxonomic
distance between the species.

9. Conti………
•3. Serum molecules: The complement system consists
of approximately 30 serum molecules constituting
nearly 10 percent of the total serum proteins (plasma or
blood proteins,) and forming one of the major defence
systems of the body.
•A series of circulating and self-cell surface regulatory
proteins keep the complement system in check.

10. Conti………
•4. Heat labile: Complement as a whole is heat labile, its
cytolytic activity undergoing spontaneous denaturation
slowly at room temperature and being destroyed in 30
minutes at 56°C though some of its components are heat
stable.
•A serum deprived (depressed) of its complement activity
by heating at 56°C for 30 minutes, is then said to be
‘inactivated’.

11. Conti………
•5. Complement fixation, binding or consumption:
Complement (C) ordinarily does not bind to free antigen
or antibody but only to antibody which has combined
with its antigen.
•Various terms such as fixation, binding or consumption
have been used to refer to the combination of C with
bound immunoglobulin, leading to the activation of the
classical C pathway.

12. Conti……….
•All classes of Ig do not fix complement. Only IgM, IgG3,
1 and 2 (in that order) fix complement, but not IgG4, IgA,
IgD or IgE.
6. Site of complement binding: The site of complement
binding is located on the Fc piece of the Ig molecule
(CH2 — domain on IgG, CH4 on IgM), and is expressed
only when Ig is combined with its antigen.
The fixation of complement is not influenced by the nature
of antigens, but only by the class of immunoglobulins.

13. Components of Complement
•The complement system comprises a group of serum
proteins, many of which exist in inactive forms.
•The complement system consists of at least twenty
chemically and immunologically distinct serum proteins
comprising the complement components, the properdin
system and the control proteins.
There are nine components of complement called C1 to
C9.

14. Conti……….
•The fraction (small parts) C1 occurs in serum as a calcium
ion dependent complex, which on chelation (to bind.)
with EDT A yields three protein subunits called C1q, r,
and s.
•Thus, C is made up of a total of 11 different proteins.
•C fractions are named C1 to C9 in the sequence of the
cascading reaction, except that C4 comes after C1, before
C2.

15. C3b
C3b is an opsonin
Opsonins are molecules
that bind both to bacteria
and phagocytes
Opsonization increases
phagocytosis by 1,000 fold.
C3b s attached to
microbial surface
microbe

16.  C4b-2a-3b functions as the classical
C5 convertase:

17. FORMATION OF MEMBRANE ATTACK COMPLEX
C5b
Cell membrane
Pathogen

18. C6
Cell membrane
Pathogen

19. Cell membrane
Pathogen
C7

20. Cell membrane

21. Cell membrane
Pathogen
C8

22. Cell membrane
Pathogen
C9

23. Cell membrane
Pathogen

24. Cell membrane
Pathogen

25. Cell membrane
Pathogen

26. Cell membrane
Pathogen

27. Cell membrane
Pathogen

28. Cell membrane
Pathogen

30. Functions of C3a and C5a
 C3a and C5a increases the inflammatory response by binding to mast cells
and causing them to release histamine.
 Most powerful chemotactic factor known for leukocytes.
Neutrophil
Macrophage
Granules
containing
inflammato
ry agents
like
histamine

31. The Alternative Pathway

 Also called as Properdin pathway
 Part of innate immunity.
 Antibody Independent.
 The alternative pathway is slower than the
Classical pathway.
 Molecules of C3 undergo cleavage at continuous
low level in normal plasma.

32. Activation of Alternative
pathway
 C3 contains in unstable thioester
bond.
 This unstable bond makesC3
subject to slow spontaneous
hydrolysis to C3b and C3a
 The C3b is able to bind to foreign
surface antigens.
 Mammalian cells contain sialic
acid which inactivates C3b

33. Factor B
 C3b on the surface of a
foreign cells binds to
another plasma protein
called factor B
 This binding of Factor B
results in the exposure
of a binding site for
another enzyme called
Factor D

34. Factor D
 The binding of factor B to
C3b allows a protein
enzyme called Factor D to
cleave Factor B to Ba and
Bb.
 Factor Bb remains bound
to C3b while Ba and Factor
D disperse away.
 The complex C3bBb is
C3 convertase of
alternative pathway
Ba

36. Properdin- Factor P
 Stabilizes C3b-Bb so it may cleave more C3.
May cleave over a million C3 molecules!
 Protects Bb-C3b from inactivation by
complement control mechanisms.

37. C5 activation
 C3b-C3b-Bb functions as the C5 convertase in the
alternative pathway.

38. MAC formation

39.  Independent of antibodies.
 Lectins are proteins that bind to specific cb targets.
 Activated by Mannose binding lectin (MBL) – lectin that
binds to mannose residues on the microbes.
 MBL is similar to C1q in structure and function.
Lectin Binding Pathway


40. Activation of lectin
pathway
 First step is binding of Mannose Binding
Lectin (MBL) to mannose residue on the
surface of microbes.
 To the MBL bound to microbe, MBL –
Associated Serine Proteases (MASP – 1 and
MASP – 2) will bind.
 MASP 1 and 2 is similar in structure and
function to C1s andC1r
 This complex will cleave C4 and C2

43. 
 1. Facilitates Opsonization :
Extremely important when pathogen carries a
capsule.
Effector functions of complement
system

44. 2.Cell lysis

45. 3. Immune complex clearance

46. and C3b
4. Inflammatory response and chemotaxis

47. OVERVIEW

48. THANK YOU