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COMPLEMENT THE LINK BETWEEN NON-SPECIFIC AND SPECIFIC IMMUNITY
Complement: History ,[object Object],[object Object],[object Object],The Nobel Prize in Physiology or Medicine 1919
resistant active immunization blood sample Bordet's Classical Experiment serum  (antisera) Fresh serum Serum (Heat inactivated at 56º C)
Hans Joaquim Muller-Eberhard (May 5, 1927- March 3, 1998).
[object Object],[object Object],[object Object],[object Object],[object Object]
Complement Functions ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Complement Components ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Pathways of Complement Activation CLASSICAL PATHWAY LECTIN PATHWAY ALTERNATIVE PATHWAY Activation of C5 MEMBRANE ATTACK COMPLEX (MAC) antibody dependent (Ac-Ag) antibody Independent (No Ac-Ag) Activation of C3 and generation of C5 convertase
Classical Pathway. C1 C1r C1s 1 2 3 4 5 6 Collagen- like tails C1q
Classical Pathway. Intact C1
Classical Pathway. Intact C1
Classical Pathway. Interaction with Ac Ac Ac Cell membrane Ag
 
Classical Pathway Ab C1qrs C4 b C4a
Ab C1qrs C4 b C2 b a
C4b2b (C3 convertase) Ab C1qrs C2 b C4 b
The Third Component of the Complement (C3) ,[object Object],[object Object],[object Object],[object Object],C3 b
C2 b C4 b C3 C3 C3 C3
b C4b2b3b (C5 convertase) C2 b C4 b C3 C3 C3 C3 a
Generation of C5 convertase  leads to the activation of the lytic pathway Lytic pathway
b C2 b C4 b C3 C3 b C5 b a C5 b a
b C8 C9 Lysis and cell death C5b C6 C7
Membrane Attack Complex
Membrane Attack Complex
 
Membrane Attack Complex
Membrane Attack Complex
 
Alternative  Pathway C3 is spontaneously formed in serum C3 b C3 b C3 b C3 b C3 b C3 b
LPS LPS Bacterial surface Lipopolysaccharide C3 b C3 b
LPS Bacterial surface C3bBb (C3 convertase) b C8 C9 C3 b B a D C3 b P C5b C6 C7
 
Mannose-Binding Protein Pathway Macrophages
Mannose-Binding Protein Pathway Bacterial Surface (rich in carbohydrates) MBP MASP-1 MASP-2 C4 b C4a
Mannose-Binding Protein Pathway Bacterial Surface (rich in carbohydrates) MBP MASP-1 MASP-2 b C4 b C2 b a
 
 
Opsonization and Phagocytosis
Biological Effects of C5a
 
 
Biological Properties of  C-activation Products Product Biological Effects Regulation C2b (prokinin) edema C1-INH C3a (anaphylatoxin) mast cell degranulation; enhanced vascular permeability;  anaphylaxis carboxy-peptidase- B (C3-INA)
Biological Properties of  C-activation Products Product Biological Effects Regulation as C3, but less potent (C3-INA) C4a (anaphylatoxin) opsonization; phagocytosis C4b (opsonin) C4-BP, factor I C3b (opsonin) opsonization; phagocyte activation factors H & I
Biological Properties of  C-activation Products Product Biological Effects Regulation anaphylactic as C3, but much more potent; attracts & activates PMN causes neutrophil aggregation, stimulation of oxidative metabolism and leukotriene release C5a ( chemotactic factor ) carboxy-peptidase-C (C3-INA) C5b67 protein-S chemotaxis, attaches to other membranes
 
C1-inhibitor deficiency: angioedema
 
 

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Linking Specific and Non-Specific Immunity via the Complement System