1. Immunoglobulin Structure and Function By Associate Lecturer Mortadha H AL-Hussainy Faculty of Veterinary Medicine Kufa University

2. Immunogobulin, Ig What is Immunoglobulin? Immunoglobulin 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 α1α1 α2α2 β γ + - albumin globulins Mobility Amount of protein

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

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 –V L & C L –V H & C H Hinge Region C H1 VLVL CLCL VHVH C H2 C H3 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 V H and V L 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) Ig-α Ig-β Ig-α

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