The document discusses the complement system, which consists of three pathways - the classical, alternative, and lectin pathways. When activated via one of these pathways, complement proteins are activated in a cascade pattern, forming complexes that opsonize pathogens, enhance inflammation and antibody responses, and directly attack pathogens. The membrane attack complex is the final product of complement activation, forming pores in pathogen membranes that cause lysis.

1. COMPLEMENT SYSTEM
COMPLEMENT SYSTEM
• Classical Pathway
• Alternative Pathway
• Lectin Pathway
NALI SOMASHEKAR SANTHOSH

2. 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
• Complement means helps
• Complement system formed about 30 different types of proteins(β –
globulins).Of these about 16 are biologically important.

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

4. 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.

5. 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.

6. 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.

7. 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
passes through three distinct
 When the compliment system is activated,it
pathways.They are
 Classical Pathway
 Alternative pathway
 Lectin pathway

8. 4 STAGES IN ACTIVATION OF COMPLEMENT
PATHWAYS
Initiation of pathway
Formation of C3 convertase
Formation of C5 convertase
Formation of MAC

9. 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.

10. • 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.

11. 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.

12. • 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.

13. 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

14. 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

15. 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

16. 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

17. CONCLUSION