Immunoglobulins:

Structure and Function

Glycoprotein molecules that are produced by

plasma cells in response to an immunogen and
which function as antibodies
105 antibody
molecules per cell

Secretion of 2000
molecules per second
after activation

General Functions of
Immunoglobulins
1. Ag binding
Can result in protection
Valency

2. Effector functions (Usually require Ag

binding)
Fixation of complement
Binding to various cells

Immunoglobulin Structure
Heavy & Light
Chains
Disulfide bonds
Inter-chain
Intra-chain

Disulfide bond

Carbohydrate

CL
VL
CH2

CH1
VH

Hinge Region

CH3

Immunoglobulin Structure
Disulfide bond

Variable &
Constant Regions
VL & CL
VH & CH

Carbohydrate

CL
VL

Hinge Region

CH2

CH1

VH

Hinge Region

CH3

Immunoglobulin Structure
Domains

Disulfide bond

VL & CL
VH & CH1 - CH3

Carbohydrate

CL

Oligosaccharides

VL
CH2

CH1

VH

Hinge Region

CH3

IgG molecule

Structure of the Variable Region

Variability Index

Hypervariable (HVR) or complimentarity

determining regions (CDR)
HVR3
150

100

HVR2

HVR1
50

FR2

FR1

25

FR3

75
50
Amino acid residue

Framework regions

FR4

100

Immunoglobulin Fragments:
Structure/Function Relationships
Fab

Papain

Ag binding
Valence = 1
Specificty
determined by VH
and VL

Fc
Effector functions

Fc
Fab

Immunoglobulin Fragments:
Structure/Function Relationships
Ag Binding

Complement Binding Site

Binding to Fc
Receptors
Placental Transfer

Immunoglobulin Fragments:
Structure/Function Relationships
Pepsin

Fab
Ag binding

Fc
Effector functions

F(ab)2
Fc
Peptides
F(ab)2

Human Immunoglobulin Classes

Based on the amino acid sequence in the constant
region of heavy chain

IgG - Gamma heavy chains

IgM - Mu heavy chains
IgA - Alpha heavy chains
IgD - Delta heavy chains
IgE - Epsilon heavy chains

Human Immunoglobulin Subclasses

IgG Subclasses

IgG1 - Gamma 1 heavy chains

IgG2 - Gamma 2 heavy chains
IgG3 - Gamma 3 heavy chains
IgG4 - Gamma 4 heavy chains

IgA subclasses
IgA1 - Alpha 1 heavy chains
IgA2 - Alpha 2 heavy chains

Human Immunoglobulin
Light Chain Types
On the basis of amino acid sequence in the
constant region of light chain

Kappa
Lambda
Light Chain Subtypes
Lambda 1
Lambda 2
Lambda 3
Lambda 4

Immunoglobulins
Nomenclature
IgM (kappa)
IgA1(lambda 2)
IgG

Heterogeneity
Various types and subtypes
Can have different antigen binding properties

Structure and properties of IgG class

and subclasses
Structure
Monomer (7S)

IgG1, IgG2 and IgG4

IgG3

 Structure
Properties
Major serum Ig (~75%)
Placental transfer through receptors on
placental cells (IgG2)
Fixes complement (IgG4)
Binds to Fc receptors (IgG2, IgG4)
Phagocytes - opsonization
K cells - ADCC

Phagocytosis

K cell: Antibody dependent bodys

defense cell
ADCC by K cells

IgM
Structure

J Chain

Pentamer (19S)
Extra domain (CH4)
J chain
CH4

Valency: 10

IgM
Structure
Properties
3rd highest serum Ig
First Ig made by foetus
and B cells
Fixes complement

Fixation of C1 by IgG and IgM Abs

No activation

Activation

IgM
Structure
Properties
3rd highest serum Ig
First Ig made by fetus
and B cells
Fixes complement
Agglutinating Ig
Binds to Fc receptors
Monomeric B cell
surface Ig

20 aa
Tail
Piece

B Cell Antigen Receptor (BcR)

Ig- Ig-

Ig- Ig-

Membrane
proteins

IgA (11S immunoglobulin)

Structure
Serum - monomer
Secretions (sIgA)
Dimer
J chain
Secretory component

Secretory Piece
(T Piece)

J Chain

Origin of Secretory Component of sIgA

IgA is made in plasma cells

T Piece made by epithelial cells, and

added to IgA as it passes into the
secretions
Helps in transportation across the
mucosa
Protects from degradations

IgA
Structure
Properties
2nd highest serum Ig
Major secretory Ig (Mucosal or Local Immunity)
Tears, saliva, gastric secretions

Does not fix complement (unless aggregated)

Binds to Fc receptors on some cells

IgD
Structure
Monomer
Tail piece
Tail Piece

IgD
Structure
Properties
4th highest serum Ig
B cell surface Ig acts as receptor for antigens
Tail piece associated with membrane proteins
Ig- and Ig-
Does not bind complement

IgE
Structure
Monomer
Extra domain (CH4)

CH4

IgE
Structure
Properties
Least common serum Ig
Binds tightly to basophils and mast cells through
receptors (Does not require Ag binding)

Involved in allergic reactions

Useful in parasitic helminth diseases
Binds to Fc receptor on eosinophils

Does not fix complement