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Physiologic function of Abs is defence against extracellular microbes and microbial toxins
Defects in Ab production result in increased susceptibility to infections
Ab mediated elimination of Ags requires participation of other effector systems
Produced Abs in lymphoid organs , perform their effector functions at sites distant from their production
Many of the effector functions of Abs are mediated by the heavy chain constant regions of Igs and different isotypes serve different effector functions
The requirement for Ag binding ensures that Abs activate various effector mechanisms only when they are needed
• Host benefit:– opsonization to enhance phagocytosis– phagocyte attraction and activation– lysis of bacteria and infected cells– regulation of antibody responses– clearance of immune complexes– clearance of apoptotic cells
• Host detriment:– Inflammation, anaphylaxis
• C1(qrs), C2, C3, C4, C5, C6, C7, C8, C9
• factors B, D, H and I, properdin (P)
• mannose binding lectin (MBL), MBL associated serine proteases (MASP-1 MASP-2)
• C1 inhibitor (C1-INH, serpin), C4-binding protein (C4-BP), decay accelerating factor (DAF), Complement receptor 1 (CR1), protein-S (vitronectin)
CLASSICALPATHWAY
ALTERNATIVEPATHWAY
activationof C5
LYTIC ATTACKPATHWAY
antibodydependent
LECTINPATHWAY
antibodyindependent
Activation of C3 andgeneration of C5 convertase
C4b
Mg++
C4a
Ca++
C1r C1s
C1q
C2b
C2a
C3
C3a
b
________
C4b2a3b is C5 convertase; it leads into the Membrane
Attack Pathway
CR-I promote phagocytosis CR-II coreceptor for B cell activation CR-III phagocytosis CR-IV phagocytosis
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Product Biological Effects Regulation
C3a (anaphylatoxin)
mast cell degranulation; enhanced vascular permeability; anaphylaxis
carboxy-peptidase- B (C3-INA)
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
a( hereditary (relatively rare) b)acquired deficiency c) increased consumption d) decreased production Complement protein levels are usually
increased, along with other unrelated proteins called acute phase proteins, during acute or chronic inflammation
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Recurrent microbial infections (usually bacterial) Autoimmune diseases, including SLE and vasculitis Hereditary angioedema Acquired angioedema Various types of kidney disease, including:
glomerulonephritis, lupus nephritis, membranous nephritis, IgA nephropathy
Malnutrition Septicemia Serum sickness (immune complex disease)
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