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By
Prof. S.B Zailani
Chief Consultant Clinical Microbiologist
OUTLINE
 INTRODUCTION
 BIOLOGICAL FUNCTIONS OF COMPLEMENT
 CLASSICAL PATHWAY
 MB LECTIN PATHWAY
 ALTENATE PATHWAY
 REGULATORY MECHANISMS
INTRODUCTION
 DEFINITION- The complement system is a complex
group of plasma proteins that interact with each other
in a cascading fashion to protect the host against
infectious agents or foreign protein(non-self antigen)
 It plays a major role in host defence and the
inflammatory process.
 Complement describes a system of about 20 proteins,
many of which are enzyme precursors. The principal
actors in this system are 11 proteins designated C1
through C9, B, and D,• All these are present normally
among the plasma proteins in the blood as well as
among the proteins that leak out of the capillaries into
the tissue spaces.• The enzyme precursors are normally
inactive, but they can be activated mainly by the so-
called classic pathway.
 They are present in a normal serum and are thus part
of innate immune defences of the body
 They are synthesize by the hepatocytes and tissue
macrophages, except C1 which is formed in GIT
epithelium
 Complement is activated sequentially in a cascading
manner, each protein activating the protein that
directly follows it in the sequence. Complement
proteins are not antibodies but the cascade is activated
by antibodies and other non immunological means
 Activation has widespread physiologic and
pathophysiologic effects. It causes lysis of RBCs in
haemolytic anaemias, sensitizes foreign particles to
phagosytosis and causes release of histamine from
mast cells
 Activation of complement on foreign
cells(microbes,RBCs, tumour cells) surfaces result in
their lysis and together with immunoglobulins some of
the complement components act as opsonin which
enhance phagocytosis.
BIOLOGICAL FUNCTIONS OF COMPLEMENT
 Opsonization---------C3b
 Inflamatory function (chemotaxis)---- C5a
 Anaphylotoxins production-------------C5a, C4a,C3a
 Cytolysis----MAC (C5b-C9)

REGULATORY MECHANISMS
 C1 inactivator
 Factor I ------- cleaves C3b and C4b fragment
 Factor H------- enhances the effect of factor I
 Properdin------stabilizes C3 convertase
 Anaphylotoxin inactivator
 Membrane cofactor protein*
 Decay accelerating factor*
*accelerate the dissociation of complement proteins
 S protein(vitronectin)-----protect the target cells from lysis
to some extent
Summary
 Thank you for your attention

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COMPLEMENT SYSTEM.pptx

  • 1. By Prof. S.B Zailani Chief Consultant Clinical Microbiologist
  • 2. OUTLINE  INTRODUCTION  BIOLOGICAL FUNCTIONS OF COMPLEMENT  CLASSICAL PATHWAY  MB LECTIN PATHWAY  ALTENATE PATHWAY  REGULATORY MECHANISMS
  • 3. INTRODUCTION  DEFINITION- The complement system is a complex group of plasma proteins that interact with each other in a cascading fashion to protect the host against infectious agents or foreign protein(non-self antigen)  It plays a major role in host defence and the inflammatory process.
  • 4.  Complement describes a system of about 20 proteins, many of which are enzyme precursors. The principal actors in this system are 11 proteins designated C1 through C9, B, and D,• All these are present normally among the plasma proteins in the blood as well as among the proteins that leak out of the capillaries into the tissue spaces.• The enzyme precursors are normally inactive, but they can be activated mainly by the so- called classic pathway.
  • 5.  They are present in a normal serum and are thus part of innate immune defences of the body  They are synthesize by the hepatocytes and tissue macrophages, except C1 which is formed in GIT epithelium
  • 6.  Complement is activated sequentially in a cascading manner, each protein activating the protein that directly follows it in the sequence. Complement proteins are not antibodies but the cascade is activated by antibodies and other non immunological means  Activation has widespread physiologic and pathophysiologic effects. It causes lysis of RBCs in haemolytic anaemias, sensitizes foreign particles to phagosytosis and causes release of histamine from mast cells
  • 7.  Activation of complement on foreign cells(microbes,RBCs, tumour cells) surfaces result in their lysis and together with immunoglobulins some of the complement components act as opsonin which enhance phagocytosis.
  • 9.  Opsonization---------C3b  Inflamatory function (chemotaxis)---- C5a  Anaphylotoxins production-------------C5a, C4a,C3a  Cytolysis----MAC (C5b-C9)
  • 10.
  • 11.
  • 12.
  • 13.
  • 14.
  • 15.
  • 16.
  • 17.
  • 18.
  • 19.
  • 20.
  • 21.
  • 22.
  • 23.
  • 24.
  • 25.
  • 26.
  • 27. REGULATORY MECHANISMS  C1 inactivator  Factor I ------- cleaves C3b and C4b fragment  Factor H------- enhances the effect of factor I  Properdin------stabilizes C3 convertase  Anaphylotoxin inactivator  Membrane cofactor protein*  Decay accelerating factor* *accelerate the dissociation of complement proteins  S protein(vitronectin)-----protect the target cells from lysis to some extent
  • 29.  Thank you for your attention