Immunoglobulins are glycoprotein molecules produced by plasma cells in response to antigens that function as antibodies. They have a basic structure consisting of two heavy chains and two light chains held together by disulfide bonds, forming variable and constant regions. The variable regions determine antigen binding specificity, while the constant regions determine effector functions. The five major classes in humans are IgG, IgM, IgA, IgD, and IgE, which have different structures, properties, and functions in the immune response.

1. Immunoglobulins:
Structure and Function

2. Immunoglobulins:Structure and
Function
 Definition: Glycoprotein molecules that
are produced by plasma cells in response
to an immunogen and which function as
antibodies
+ -
Amount of protein
albumin
globulins
1 2   Immune serum
Ag adsorbed serum
Mobility

3. General Functions of
Immunoglobulins
• Ag binding
– Can result in protection
– Valency
 Effector functions
 Fixation of (Usually require Ag binding)
complement
 Binding to various
cells

4. Basic Immunoglobulin Structure
 Immunoglobulins - heterogeneous
 Myeloma proteins - homogeneous
immunoglobulins

5. Immunoglobulin Structure
Disulfide bond
 Heavy & Light
Chains Carbohydrate
 Disulfide bonds
 Inter-chain CL
VL
 Intra-chain
CH2 CH3
CH1
Hinge Region
VH

6. Immunoglobulin Structure
Disulfide bond
 Variable & Carbohydrate
Constant
Regions CL
VL
 VL & CL
CH2 CH3
 VH & CH CH1
Hinge Region
VH
 Hinge Region

7. Immunoglobulin Structure
Disulfide bond
 Domains
 VL & C L Carbohydrate
 VH & CH1 - CH3
(or CL
CH4) VL
CH2 CH3
 Oligosaccharides CH1
Hinge Region
VH

8. IgG molecule
Used with permission from: Dr. Mike Clark, Immunology
Division, Department of Pathology Cambridge University,
Cambridge, England

9. Structure of the Variable Region
 Hypervariable (HVR) or complimentarity
determining regions (CDR) HVR3
150
Variability Index
100 HVR2
HVR1
50
FR1 FR2 FR3 FR4
0 25 50 75 100
Amino acid residue
 Framework regions

10. Immunoglobulin Fragments:
Structure/Function Relationships
 Fab Papain
 Ag binding
 Valence = 1
 Specificty
determined by
VH and VL
 Fc
 Effector functions Fc
Fab

11. Immunoglobulin Fragments:
Structure/Function Relationships
Ag Binding
Complement Binding Site
Binding to Fc
Receptors
Placental Transfer

12. Immunoglobulin Fragments:
Structure/Function Relationships
 Fab Pepsin
 Ag binding
 Fc
 Effector
functions
 F(ab’)2
Fc
Peptides
F(ab’)2

13. Human Immunoglobulin
Classes
 IgG - Gamma heavy chains
 IgM - Mu heavy chains
 IgA - Alpha heavy chains
 IgD - Delta heavy chains
 IgE - Epsilon heavy chains

14. 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

15. Human Immunoglobulin
Light Chain Types
 Kappa ()
 Lambda ()

16. Human Immunoglobulin
Light Chain Subtypes
 Lambda light chains
 Lambda 1
 Lambda 2
 Lambda 3
 Lambda 4

17. Immunoglobulins
 Nomenclature
 IgM (kappa)
 IgA1(lambda 2)
 IgG
 Heterogeneity

18. IgG
 Structure
 Monomer (7S)
IgG1, IgG2 and IgG4 IgG3

19. IgG
 Structure
 Properties
 Major serum Ig
 Major Ig in extravascular spaces
 Placental transfer – Does not require Ag binding
(IgG2)
 Fixes complement (IgG4)
 Binds to Fc receptors (IgG2, IgG4)
 Phagocytes - opsonization
 K cells - ADCC

20. IgM
J Chain
 Structure
 Pentamer (19S)
 Extra domain (CH4)
 J chain
C4

21. IgM
 Structure
 Properties
 3rd highest serum Ig
 First Ig made by
fetus and B cells
 Fixes complement

22. Fixation of C1 by IgG and IgM Abs
C1r C1
s
C1q
C1r C1
s
C1q
No activation Activation

23. IgM
 Structure
 Properties
 3rd highest serum Ig
 First Ig made by fetus
and B cells
 Fixes complement
 Agglutinating Ig
 Binds to Fc receptors Tail
Piece
 B cell surface Ig

24. B Cell Antigen Receptor (BcR)
Ig- Ig- Ig- Ig-

25. IgA
 Structure
 Serum -
monomer
 Secretions Secretory J
(sIgA) Piece Chain
 Dimer (11S)
 J chain
 Secretory
component

26. Origin of Secretory Component of sIgA

27. IgA
 Structure
 Properties
 2nd highest serum Ig
 Major 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

28. IgD
 Structure
 Monomer
 Tail piece
Tail Piece

29. IgD
 Structure
 Properties
 4th highest serum Ig
 B cell surface Ig
 Does not bind complement

30. IgE
 Structure
 Monomer
 Extra domain (CH4)
C4

31. IgE
 Structure
 Properties
 Least common serum Ig
 Binds to basophils and mast cells (Does not
require Ag binding)
 Allergic reactions
 Parasitic infections (Helminths)
 Binds to Fc receptor on eosinophils
 Does not fix complement