Immunoglobulins are glycoprotein molecules produced by plasma cells that function as antibodies. They have a basic Y-shaped structure composed of two heavy chains and two light chains connected by disulfide bonds. The variable regions at the tips of the Y determine antigen binding specificity. The constant regions define the five major classes - IgG, IgM, IgA, IgD, and IgE - which have different effector functions like complement activation. IgG is the most abundant antibody and provides systemic immunity while IgA dominates mucosal immunity through secretions. IgE mediates allergic reactions by binding basophils and mast cells.

2. Immunoglobulins:
Structure and Function
By Dr Shamim Akram

3. 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
α1 α2 β γ
+ -
albumin
globulins
Mobility
Amountofprotein

4. General Functions of
Immunoglobulins
• Ag binding
– Can result in protection
– Valence-binding sites on Ag for Ab/ on Ab for
Ag
• Effector functions (Usually require Agbinding)
– Fixation of complement
– Binding to various cells

5. Basic Immunoglobulin Structure
• Immunoglobulins - heterogeneous
• Myeloma proteins - homogeneous
immunoglobulins

6. Immunoglobulin Structure
• Heavy & Light
Chains
• Disulfide bonds
– Inter-chain
– Intra-chain
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond

7. Immunoglobulin Structure
• Variable &
Constant Regions
– V & CL L
– VH& CH
• Hinge Region
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond

8. Immunoglobulin Structure
• Domains
– VL& CL
– VH& CH1- CH3
(or CH4)
• Oligosaccharides CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond

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

10. Structure of the Variable Region
• Hypervariable (HVR) or complimentarity
determining regions (CDR) HVR3
FR1 FR2 FR3 FR4
HVR2
VariabilityIndex
25 75 10050
Amino acid residue
150
100
HVR1
50
0
• Framework regions

11. Immunoglobulin Fragments:
Structure/Function Relationships
Papain
Fc
Fab
• Fab
– Ag binding
– Valence = 1
– Specificity
determined by VH
and VL
• Fc
– Effector functions-
destruction of pathogens/Ag

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

13. Immunoglobulin Fragments:
Structure/Function Relationships
• Fab
– Ag binding
• Fc
– Effector functions
• F(ab’)2
Pepsin
Fc
Peptides
F(ab’)2

14. Human Immunoglobulin Classes
• IgG - Gamma (γ) heavy chains
• IgM - Mu (µ) heavy chains
• IgA - Alpha (α) heavy chains
• IgD - Delta (δ) heavy chains
• IgE - Epsilon (ε) heavy chains

15. Human Immunoglobulin Subclasses
• IgG Subclasses
– IgG1 - Gamma 1 (γ1) heavy chains
– IgG2 - Gamma 2 (γ2) heavy chains
– IgG3 - Gamma 3 (γ3) heavy chains
– IgG4 - Gamma 4 (γ4) heavy chains
• IgA subclasses
– IgA1 - Alpha 1 (α1) heavy chains
– IgA2 - Alpha 2 (α2) heavy chains

16. Human Immunoglobulin
Light Chain Types
• Kappa (κ)
• Lambda (λ)

17. Human Immunoglobulin
Light Chain Subtypes
• Lambda light chains
– Lambda 1 (λ1)
– Lambda 2 (λ2)
– Lambda 3 (λ3)
– Lambda 4 (λ4)

18. Immunoglobulins
• Nomenclature
– IgM (kappa)
– IgA1(lambda 2)
– IgG
• Heterogeneity

19. IgG
• Structure
– Monomer -7S (sedimentation coefficient)
IgG1, IgG2 and IgG4 IgG3

20. IgG
• Structure
• Properties
– Major serum Ig (systemic immunity)
– Major Ig in extravascular spaces
– Placental transfer – Does not require Ag binding
(± IgG2)
– Fixes complement (± IgG4)
– Binds to Fc receptors (± IgG2, IgG4)
• Phagocytes – opsonization (enhance phagocytosis)
• K cells(produce hormone) – ADCC(Ab dependent
cellular cytotoxicity)

21. IgM
• Structure
– Pentamer (19S)
– Extra domain (CH4)
– J chain
CH4
J Chain

22. IgM
• Structure
• Properties
– 3rd highest serum Ig
– First Ig made by fetus and B cells in
acute infection
– Fixes complement

23. Fixation of C1 by IgG and IgM Abs
C1q
C1q
No activation Activation

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

25. B Cell Antigen Receptor (BcR)
Ig-αIg-β Ig-βIg-α

26. IgA
• Structure
– Serum - monomer
– Secretions (sIgA)
• Dimer (11S)
• J chain
• Secretory component
J ChainSecretory Piece

27. Origin of Secretory Component of sIgA

28. 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

29. IgD
• Structure
– Monomer
– Tail piece
Tail Piece

30. IgD
• Structure
• Properties
– 4th highest serum Ig
– B cell surface Ig
– Does not bind complement

31. IgE
• Structure
– Monomer
– Extra domain (CH4)
Cε4

32. 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