Complement system

 REGULATION
 BIOLOGICAL EFFECT
 DEFICIENCIES

 The complement system has the potential to be
extremely damaging to host tissues.
 complement control protein .
 Some complement control proteins are present
on the membranes of self-cells preventing them
from being targeted by complement.

 C1 inhibitor
 Regulators of the C3 and C5 convertases
 Factor I
 Soluble regulatory proteins; C4b-binding protein
and factor H
 Membrane regulatory proteins, CD55 (DAF), CD46
(MCP), CD35 (CR1)
 Properdin
 Regulators of the MEMBRANE ATTACK
COMPLEX
 Soluble MAC inhibitors; S protein, and clusterin
 Membrane MAC inhibitor; CD59

 C1 inhibitor {serpin} inhibits the production of
C3b by combining with the Cq1rs complex.
This prevents formation of the C3
convertase,C4b2b.
 Protein H inhibits the production of C3b
complex by inhibitingthe bindingof factor B to
membrane bound C3b
 Factor I inhibits the production of C3b by
cleavingC3b into inactive form

 Regulatory proteins promotes or inhibits
complementary activity and protect self cell
lysis.
 Decay acceleration factor[DAC] accelerates
break down of C3 convertase.
 Homologous restriction factor[HRF]prevents
insertion of C8 and C9 into membranes.

 The following are the basic functions of
complement:
 Opsonization – enhancing phagocytosis of
antigens
 Chemotaxis – attracting macrophages and
neutrophils
 Cell Lysis – rupturing membranes of foreign
cells
 Agglutination – clustering and binding of
pathogens together (sticking)

 Bacteriolysis and Cytolysis
 Amplification of inflammatory Response
 Hypersensitivity Reaction
 Endotoxic shock
 Immune adherence
 Opsonisation
 Autoimmune diseases

BACTERIOLYSIS AND CYTOLYSIS
 Complement mediates immunological
membrane damage .
 This results in bacteriolysis and cytolysis.
 Neutralisation of certain viruses requires the
partication of complement

AMPLIFICATION OF INFLAMMATORY
RESPONSE
 C3a and C5a are anaphylatoxic by
degranulation of mast cells to release
histamine and other mediators.
 They cause increased vascular permeability
and are also chemotactic
 C567 is chematactic and also brings about
reactive lysis

HYPERSENSITIVITY REACTIONS
 Complement participates in type 2 [cytotoxic]
and type 3[immune complex] hypersensity
reactions.

ENDOTOXIC SHOCK
 Endotoxin can activate the alternative pathway
of the complement cascade.
 In Endotoxin shock there is excessive C3
activation and platelet adherence.
 Platelet lysis and release of large amount of
platelets factor lead to DIC and
thrombocytopenia.
 Gram negative septicaemias and dengue
haemorrhagic syndrome may have a similar
pathogenesis
 Schwartzman reaction is a good model of
excessive C3 activation and depletion of
complement protects against this reaction

IMMUNE ADHERENCE
 Immune adherence – Complement bound to
antigen – antibody complexes adheres to
erythrocytes or to plateletes.
 Particles are rapidly phagocytosed – help in
eliminating the pathogenic microorganisms.
 C3 and C4 are necessary for immune
adherence.

OPSONISATION
 To facilitate the destruction of pathogens by
phagocytic cells – important function of
complement
 Phagocytic cells (macrophages, monocytes,
neutrophils and others) posses surface
receptors for C3b.
 If immune complexes have activated the
complement system, the C3b bound to them
stimulates phagocytosis and removal of
immune complexes.

AUTOIMMUNE DISEASES
 Serum complement levels are decreased in
many auto immune diseases such as Systematic
Lupus Erythematosus and Rheumatoid
arthritis
 They may therefore be involved in
pathogenesis of autoimmune diseases

 Deficiency defects are transmitted as
phenotypically autosomal-recessive traits.
 Deficiency of properdin is X-linked.
 Deficiency of the C1 inhibitor is inherited as an
autosomal dominant.

 All patients with complement deficiency are
more or less unduly susceptible to infection
and to development of immune complex
disease.
 Genetic deficiencies in classical pathway
components.
 Deficiencies in components of the alternative
pathway.
 Mutation of the gene encoding the mannose-
binding lectin (MBL).

 Deficiencies in the terminal complement
components.
 Deficiencies in complement regulatory
proteins.
 Deficiencies in complement receptors.

DEFICIENCY CLINICAL CORRELATION
C3 (any pathway) Autoimmune collagen vascular disease, susceptibility to
infectious diseases
Classical pathway
C1q, C1r, C1s, C4, C2 Autoimmune collagen vascular disease, susceptibility to
infectious diseases
C1,C2,C4
components
Systemic lupus erythematosus{SLE} and other collagen
vascular diseases
Alternate pathway
Factor B Meningococcemia
Factor D Recurrent pyogenic infections
Properdin Recurrent pyogenic infections, Meningococcemia

DEFICIENCY CLINICAL CORRELATION
Lectin pathway Recurent infections
Membrane attack complex
C5,C6, C7, C8 Bacteraemia ,mainly gram negative diplococci,
toxoplasmosis
C9 Susceptibility to infectious diseases
Regulatory proteins
C1 inhibitor Hereditary angionurotic oedema (Quincke's
disease)
Factor I, Factor H Autoimmune collagen vascular disease, Recurrent
pyogenic infections
CR1 SLE
DAF, HRF Paroxysmal nocturnal hemoglobinuria

Complement system

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