1. Immunoglobulin — Structure and Function
孟 明教授, PhD，MD

2. Immunogobulin, Ig What is Immunoglobulin?
Immunoglobulins are the critical ingredients of humoral acquired immune response.
The immunoglobulins are a group of glycoproteins present in the serum and tissue fluids of all mammals.

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
Amount of protein

4. General Functions of Immunoglobulins
Ag binding
Can result in protection
Valence
Effector functions
Fixation of complement
Binding to mast cells , macrophages, NK cell
(Usually require Ag binding)

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

6. Two Forms of Immunoglobulin
Membrane-bound receptor
Soluble antibody

7. Immunoglobulin Structure
Variable(V) & Constant (C) Regions
VL & CL
VH & CH
Hinge Region
CH1 VL CL VH
CH2
CH3
Hinge Region
Carbohydrate
Disulfide bond

8. Structural Regions

9. hypervariable region
also called
Complementarity Determining Regions(CDRs),

10. 超变区（ hyper-variable region, HVR),又称互补决定区(complementary determining region, CDR）

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

12. Enzymatic Digestion Products of Immunoglobulins

13. Immunoglobulin Fragments: Structure/Function Relationships
Fab
Ag binding
Valence = 1
Specificity determined by VH and VL
Papain Fc
Fab
Fc ( crystallizable)
Effector functions

16. Domains of Immunoglobulin

17. Functions of the domains on Ig： VH, VL — antigen binding sites；
CH1～3, CL — genetic markers of Ig；
CH2(IgG), CH3(IgM) — C1q binding sites；
CH2～CH3(IgG) — binding to placenta；
CH3(IgG) — FcγR binding site；
CH4(IgE) — FcεR binding site.

18. Function of Immunoglobulins
Recognition of antigen 识别抗原
Activation of complement 激活补体
Opsonization 调理作用
Antibody-dependent cell-mediated cytotoxicity,ADCC 抗体依赖性细胞毒作用
Mediate hypersensitivity type I 超敏反应

19. Immunoglobulin Classes and Subclasses
Immunglobulin molecules are divided into distinct classes and subclasses in terms of the differences in amino acid sequence of constant region of heavy chain, i.e.γ,α,μ,δ,andεchains.

20. Immunoglobulin Classes of Mammals
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

21. Five Classes of Immunoglobulin

22. IgG has a family of subclass, IgG1, IgG2, IgG3, IgG4(cattle has no)
IgA is divided into two subclasses, IgA1 and IgA2(sheep).

23. Light Chain Types of Immunoglobulin
Kappa (κ)
Lambda (λ)
All light chains have protein molecular weights of approximately 23,000 but can be divided into two distinct types, namely λchain, κchain, respectively

25. B Cell Antigen Receptor (BCR)

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

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 Properties 4th highest serum Ig B cell surface Ig
Does not bind complement

29. IgE Structure Properties Least common serum Ig Allergic reactions
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

30. To be continued

31. Isotypes, Allotypes, and Idiotypes of Immunoglobulins

32. Isotype 同种型
All the heavy chain constant region structures which give rise to classes and subclasses are expressed together in the serum of a normal subject are called Isotypic variants.
Each of those is called Isotype.

33. Allotypes 同种异型
Amino acid sequences of immunoglobulins differ from each other in a same species, and this is called inherited sequence variation.
The variations in heavy chain genes are called Allotypes.

34. Idiotypes 独特型
The variations of amino acid sequences within the variation domains on light and heavy chains are called Idiotypes.

36. Physiology of Immunoglobulins
1. IgG(in chicken IgY): opsonization, complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC).
2. IgA(chicken): mucosal immunity.
3. IgD: naive B cell antigen receptor.
4. IgM(chicken): naive B cell receptor, complement activation.
5. IgE: immediate hypersensitivity.

38. Transport Across Placenta

42. Antibody-Dependent Cell-Mediated Cytotoxicity(ADCC)

43. Phagocytosis of antibody-antigen
Neutralization
Bacterial toxins
Host cell
Toxin receptors
Neutralization by antibody
Phagocytosis of antibody-antigen
complex by macrophage
Fc receptor
Forming phagosome

44. Opsonization Extracellular bacteria Opsonization Macrophage
Ingestion by macrophage
Digestion in lysosome

45. Complement Activation
Digestion in lysosome
Bacteria in plasma
Complement
activation
Lysis and
ingestion

47. Fate of Antibody-Toxin or Antibody-Pathogen Complexes
Lysosome
Phagosome fuses with lysosome,
antigen–antibody complex
is digested by lysosomal hydrolases
Phagosome

48. Antibody Technology Polyclonal antibody Monoclonal antibody
Engineer-based antibody
single chain antibody

52. scFv (single chain V region antibody)

53. Fv (Variable region fragment)

54. Next lecture The Complement System
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The Complement System