CHAPTER 7 CELL STRUCTURE & FUNCTION PGS. 168 - 199 CELL STRUCTURE & FUNCTION.
Immunoglobulins : Structure and Function
description
Transcript of Immunoglobulins : Structure and Function
Immunoglobulins:Structure and Function
Aulanni’amBiochemistry Laboratory
Faculty of Sciences_UB
Immunoglobulins:Structure and Function
Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies
Immune serum
Ag adsorbed serum
1 2
+ -albumin
globulins
Mobility
Am
oun
t of
pro
tein
General Functions of Immunoglobulins
Effector functions Fixation of
complementBinding to various
cells
(Usually require Ag binding)
• Ag binding– Can result in protection
Basic Immunoglobulin Structure
Immunoglobulins - heterogeneous
Myeloma proteins - homogeneous immunoglobulins
Immunoglobulin Structure
Heavy & Light Chains
Disulfide bondsInter-chainIntra-chain
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
Immunoglobulin Structure
Variable & Constant RegionsVL & CL
VH & CH
Hinge RegionCH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
Immunoglobulin Structure
DomainsVL & CL
VH & CH1 - CH3 (or CH4)
Oligosaccharides
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
IgG molecule
Structure of the Variable Region
Hypervariable (HVR) or complimentarity determining regions (CDR)
HVR3
FR1 FR2 FR3 FR4
HVR1HVR2
Var
iabi
lity
Ind
ex
25 7550 100Amino acid residue
150
100
50
0
Framework regions
Immunoglobulin Fragments: Structure/Function Relationships
FabAg bindingValence = 1Specificty
determined by VH and VL
Papain
Fc
Fab
FcEffector functions
Immunoglobulin Fragments: Structure/Function Relationships
Ag Binding
Complement Binding Site
Placental Transfer
Binding to Fc Receptors
Immunoglobulin Fragments: Structure/Function Relationships
FabAg binding
FcEffector functions
F(ab’)2
Pepsin
Fc Peptides
F(ab’)2
Human Immunoglobulin Classes
IgG - Gamma () heavy chains
IgM - Mu () heavy chainsIgA - Alpha () heavy chainsIgD - Delta () heavy chainsIgE - Epsilon () heavy chains
Human Immunoglobulin Subclasses IgG Subclasses
IgG1 - Gamma 1 (1) heavy chainsIgG2 - Gamma 2 (2) heavy chainsIgG3 - Gamma 3 (3) heavy chainsIgG4 - Gamma 4 (4) heavy chains
IgA subclassesIgA1 - Alpha 1 (1) heavy chainsIgA2 - Alpha 2 (2) heavy chains
Human ImmunoglobulinLight Chain Types
Kappa ()Lambda ()
Human ImmunoglobulinLight Chain Subtypes
Lambda light chainsLambda 1 (1)Lambda 2 (2)Lambda 3 (3) Lambda 4 (4)
Immunoglobulins
NomenclatureIgM (kappa)IgA1(lambda 2)IgG
Heterogeneity
IgG
StructureMonomer (7S)
IgG1, IgG2 and IgG4 IgG3
IgGStructureProperties
Major serum IgMajor Ig in extravascular spacesPlacental transfer – Does not require Ag
binding ( IgG2)Fixes complement ( IgG4)Binds to Fc receptors ( IgG2, IgG4)
Phagocytes - opsonizationK cells - ADCC
IgM
StructurePentamer (19S)Extra domain (CH4)
J chainC4
J Chain
IgM
StructureProperties
3rd highest serum IgFirst Ig made by fetus
and B cellsFixes complement
Fixation of C1 by IgG and IgM Abs
C1r C1s
C1qC1r C1s
C1q
No activation Activation
IgM
StructureProperties
3rd highest serum IgFirst Ig made by fetus
and B cellsFixes complement
Tail Piece
Agglutinating IgBinds to Fc receptorsB cell surface Ig
B Cell Antigen Receptor (BcR)
Ig-Ig- Ig-Ig-
IgA
StructureSerum - monomerSecretions (sIgA)
Dimer (11S)J chainSecretory
component
J ChainSecretory Piece
IgA
StructureProperties
2nd highest serum IgMajor secretory Ig (Mucosal or Local Immunity)
Tears, saliva, gastric and pulmonary secretions
Does not fix complement (unless aggregated)Binds to Fc receptors on some cells
IgD
StructureMonomerTail piece
Tail Piece
IgD
StructureProperties
4th highest serum IgB cell surface IgDoes not bind complement
IgE
StructureMonomerExtra domain (CH4)
C4
IgE
StructureProperties
Least common serum IgBinds to basophils and mast cells (Does not
require Ag binding)Allergic reactionsParasitic infections (Helminths)
Binds to Fc receptor on eosinophilsDoes not fix complement