Effector mechanisms of humoral immunity

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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

Neutralization of microbes and microbial toxins

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Opsonization

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Antibody-dependent cell- mediated cytotoxicity

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• 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

C4C2 C3

C1 complex

Ca++

C1r C1s

C1q

Ca++

C1r C1s

C1q

C4

C4a

b

C4b

Mg++

C4a

Ca++

C1r C1s

C1q

C2

C2ba

C2a

_____

C4b2a is C3 convertase

C4b

Mg++

C4a

Ca++

C1r C1s

C1q

C2b

C2a

C3

C3a

b

________

C4b2a3b is C5 convertase; it leads into the Membrane

Attack Pathway

Generation of C5 convertase leads to the activation of the

Lytic pathway

Lytic pathway

C6

C9

C8

C7C5

C3b C2 aC4b

C5 b

C5a

C5 b

C6

C7

C5 b

C6

C7C8

C9

C9

C9

C9C9

C9 C

9C9

C9

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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