Effector mechanisms of humoral immunity 1 Physiologic function

Effector mechanisms of humoral immunity 1

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 3

4

5

Opsonization 6

Antibody-dependent cell- mediated cytotoxicity 8

10

11

• 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

• C 1(qrs), C 2, C 3, C 4, C 5, C 6, C 7, C 8, C 9 • factors B, D, H and I, properdin (P) • mannose binding lectin (MBL), MBL associated serine proteases (MASP-1 MASP-2) • C 1 inhibitor (C 1 -INH, serpin), C 4 -binding protein (C 4 -BP), decay accelerating factor (DAF), Complement receptor 1 (CR 1), protein. S (vitronectin)

CLASSICAL PATHWAY antibody dependent LECTIN PATHWAY ALTERNATIVE PATHWAY antibody independent Activation of C 3 and generation of C 5 convertase activation of C 5 LYTIC ATTACK PATHWAY

C 1 r C 1 s Ca++ C 1 q C 2 C 1 complex C 3 C 4

C 1 r C 1 s Ca++ C 1 q C 4 b C 4 a

C 4 a C 1 r C 1 s Ca++ C 1 q a 2 C C 2 b _____ Mg++ C 4 b 2 a is C 3 convertase C 4 b C 2 a

C 4 a C 1 r C 1 s Ca++ C 1 q Mg++ C 2 b C 3 a ____ C 4 b 2 a 3 b is C 5 convertase; it leads into the Membrane Attack Pathway C 4 b C 2 a C 3 b

Lytic pathway Generation of C 5 convertase leads to the activation of the Lytic pathway

C 7 C 6 C 5 C 8 C 9

C 5 a C 5 b C 4 b C 2 a C 3 b

C 6 C 7 C 5 b

C 6 C 8 CC C 9 9 9 9 C 9 C C C 9 9 C 7 C 5 b

CR-I promote phagocytosis CR-II coreceptor for B cell activation CR-III phagocytosis CR-IV phagocytosis 24

Product Biological Effects Regulation C 3 a (anaphylatoxin) mast cell degranulation; carboxypeptidase- B enhanced vascular (C 3 -INA) permeability; anaphylaxis

Product Biological Effects Regulation C 3 b (opsonin) opsonization; phagocyte activation factors H & I C 4 a as C 3, but less (anaphylatoxin) potent (C 3 -INA) C 4 b (opsonin) C 4 -BP, factor I opsonization; phagocytosis

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 29

DECREASED COMPLEMENT LEVELS MAY BE SEEN WITH: 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, Ig. A nephropathy Malnutrition Septicemia Serum sickness (immune complex disease) 30