Immunoglobulins aimec

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