Complement system - Classical, Alternate and Lectin pathways

1. IMMUNOLOGY ASSIGNMENT
COMPLEMENT SYSTEM
• Classical Pathway
• Alternative Pathway
• Lectin Pathway
Submitted To,
Jenitha Ma’am
Department of Microbiology
Submitted By,
Vaishnavi V
II Msc Microbiology
Scott Christian College
Nagercoil

2. Found in serum
and normal
body fluids
Neither
Ag nor Ab
β-globulins
COMPLEMENT
Complex
proteins
5% of
normal
serum
proteins
Exists as
proenzyme
Has no
cell
Circulate in
the blood as
inactive forms
Species – non
specific
Binds to fc
region of
antibody
Denatured by
heating the serum
at 56°c for 30 min
» inactivated
serum
Important
topic

3. COMPLEMENT
• Group of large thermolabile enzymatic proteins found in the serum and
body fluids
• It completes the antigen-antibody reaction, lysis and phagocytosis
• Represented as C
• Discovered by Bordet in 1895 named as Alexin
• Ehrlich in 1980 coined the term Complement
• Complement means helps

4. • Activated components shown by putting a bar over them.Eg.𝐶4
• Inactive forms of complement components indicated by the suffix ‘i’. Eg.C4i
, C3i.
• Complement system formed about 30 different types of proteins(β –
globulins).Of these about 16 are biologically important.
• Complement links innate immunity and adaptive immunity
COMPONENT ACTIVATOR
• The complement cascade is a series of reactions in which the preceding
components act as enzymes on the succeeding components.

5. FUNCTION
They act in the following ways:
 Complements kill opsonized pathogens.
 They include inflammatory responses.
 They enhance antibody response.
 They attack some pathogens directly.

6. Complement performs a number of protective
functions such as:
• It brings about bacteriolysis and haemolysis in co-operation with
antigen-antibody complex.
• It helps in the phagocytosis of microorganisms by phagocytes.
• It detoxifies the endotoxins of microbes.
• It brings about the coagulation of blood by converting prothrombin
into thrombin.

7. COMPLEMENT SYSTEM = 30 SERUM PROTEINS
Complement
Components
Properdin
System
Regulatory
Proteins
• C1 – C9
• C1 C1q, C1r, C1s

8. BIOSYNTHESIS OF COMPLEMENTS
• Complement components are synthesized in various sites in the
body.
• Major site – Liver
• Minor site – Blood Monocytes, Tissue Macrophages, Epithelial Cell Of
GIT, Genito-urinary Tract
• C1 is synthesized in the intestinal epithelium.
• C2 and C4 are synthesized from macrophages.
• C3, C6 and C9 are synthesized in the liver.
• The site of synthesis of C7 is not known.

9. COMPLEMENT ACTIVATION
• Complement proteins inactive form blood plasma.
• Complement components activated by activating substances or
activating agents.
• antigen-antibody complexes, gram negative bacteria, animal
viruses, aggregated antibodies like IgG or IgA endotoxin, yeast , etc.
• One component is activated ,other components triggered in
sequence, in cascade pattern to bring biological activity lysis,
phagocytosis, etc.

10. When a component is activated,it acquires the following
unique properties:
• The activated complement binds on to the biological membrane such
as the membrane of a bacterium.
• It generates enzyme activity.
• It activates the next complement protein in order to participate in a
chain reaction.

11. ACTIVATION
• To activate the inactive proteins
Complement proteins (inactivate)
Proteolysis
Larger fragment (b) smaller fragment (a)
Participate in cascade reaction removed
• Exception : C2a larger fragment participate

12. The smaller fragment usually possesses biological
effects such as:
• Defense mechanisms.
• Amplifying the inflammatory process.
• Increasing vascular permeability.
• Inducing smooth muscle contraction.
• Causing chemotaxis of leukocytes.
• Promoting viral neutralization.
• Detoxifying endotoxins.
• Effecting the release of histamine from mast cells.

13. COMPLEMENT PATHWAY
CLASSICAL PATHWAY
• Ab dependent
• Triggered by Ag-Ab
complex
ALTERNATE PATHWAY
• Ab independent
• Triggered by Ag
directly
LECTIN PATHWAY
• Resembles classical
pathway ; Ab
independent
• Triggered by Ag
directly
 When the compliment system is activated,it passes through three distinct
pathways.They are
 Classical Pathway
 Alternative pathway
 Lectin pathway

14. 4 STAGES IN ACTIVATION OF COMPLEMENT
PATHWAYS
Initiation of pathway
Formation of C3 convertase
Formation of C5 convertase
Formation of MAC

15. CLASSICAL PATHWAY
• Simple stepwise immunological reaction of complements activated by
antigen-antibody complex.
• The 11 components react in the following sequence : C1q, C1r, C1s,
C4, C2, C3, C5, C6, C7, C8, C9
• Activated by antigen-antibody complex,produced in humoral immune
response.
• The antibody produced in response to a pathogen , binds to the
pathogen to form antigen-antibody complex.

16. • Antigen-antibody complex is recognized by C1 and it binds to the
complex.
• C1 activates C4 and C2 to form C3 convertase.
• C3 convertase activities C3 and other complements in a sequence to
form MACs (Membrane attack complex).
• The MACs are deposited on the pathogen and they make holes on the
pathogen.
• The holes make the lysis of the pathogen.

18. ALTERNATIVE PATHWAY
• Stepwise immunological reaction of complements activated by
properdin.
• Properdin (a normal serum protein) reacts with zymosan (a
polysaccharide from yeast cell wall) to form PZ complex.
• 6 complement components involved are C3,C5,C6,C7,C8 and C9.
• PZ complex cleaves the C3 into C3a and C3b.
• C3b is coated on the surface of microbe.

19. • The factor B binds with C3b to form C3bB complex and it is stabilized
and activated by the factors P and D to form C3 convertase.
• C3 convertase activates more C3 and other complements in a
sequence to form MACs (Membrane attack complex).
• The MACs are deposited on the pathogen and they make holes on the
pathogen.
• The holes make the lysis of the pathogen.

21. LECTIN PATHWAY
• Immunological reaction of complements activated by lectin
• 8 components involved C2,C4,C3,C5,C6,C7,C8,C9
• Lectin binds with mannose of pathogen
• This binding activates MASP-1 which activates MASP-2
• MASP-2 activates C4 and C2 to form C3 convertase
• C3 convertase activates C3 and other complements in a sequence to
form MAC
• MACs deposited on pathogen ; make holes lysis of pathogen

23. MAC
MEMBRANE ATTACK COMPLEX
• Complex of proteins; formed by the activation of complement system
• Deposited on the surface of pathogen to make holes
• holes lysis of pathogen
• End product of complement activation
• Effector protein of immune system
• Makes transmembrane channel on the plasma membrane of
pathogens
• Channels disrupt phospholipid bilayer of pathogen lysis

24. STRUCTURE
• Complex of 5 complement proteins
C5b, C6, C7, C8, C9
• C5b, C6, C7, C8 Bind outer surface of the plasma membrane
• C9 copies hook up together to form ring in the membrane
• Ring structure pores in the membrane
• Pores allows diffusion causing lysis
FUNCTION
• Cytolysin makes pores on pathogen
• Lysis of pathogen

25. STRUCTURE OF MAC

26. FUNCTION
Opsonization • C3b & C1q; enhance phagocytosis
Chemotaxis • C5a and C5,6,7 complex ; attract neutrophils • C5a –
enhance adhesiveness of neutrophils to the endothelium
Anaphylatoxin (C3a, C4a, C5a) • Cause degranulation of mast cells •
Bind directly to smooth muscles of bronchioles ; bronchospasm
Opsonins are molecules that bind both to bacteria and phagocytes
Opsonization increases phagocytosis by 1,000 fold.
Disrupt the membrane & the entry of water and electrolytes into the
cell
Enhancement of antibody production • Binding of C3b to its
receptors on the surface of activated B cells ; enhanced antibody
production

27. CONCLUSION