3 Immunoglobulins

Immunoglobulins – membrane-bound and soluble receptors

Immunoglobulin, Ig Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies. The immunoglobulins are a group of glycoproteins present in the serum and tissue fluids of all mammals.

Immune serum Ag adsorbed serum + - albumin globulins Mobility Amount of protein α1 α2 β γ

Amount of protein Mobility albumin globulins +-

Two Forms of Immunoglobulin Membrane-bound receptor Soluble antibody

Structure of Immunoglobulin — The Four-Chain Basic Unit

Immunoglobulins are composed of two identical heavy (H) and two identical light (L) polypeptide chains. Each H and L chain has an amino- terminal variable (V) region and a carboxyl- terminal constant (C) region.

Domains of Immunoglobulin

Structural Regions

Hinge Region and Hypervariable Regions

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

Complementarity Determining Regions(CDRs), also called hypervaraible region

Hypervaraible regions

J Chain and Secretory Component

Five Classes of Immunoglobulin

Enzymatic Digestion Products of Immunoglobulins

Immunoglobulin Classes and Subclasses 1. 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.γαμδεchains.

Accordingly, the antibodies are IgG, IgA, IgM, IgD, IgE

2. All light chains have protein molecular weights of approximately 23,000 but can be divided into two distinct types, namely λchain, κchain, respectively.

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.

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

Isotypes, Allotypes, and Idiotypes of Immunoglobulins

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.

Allotypes 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. 同种异型

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

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

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.

Transport Across Placenta

Opsonization

Antibody-Dependent Cell-Mediated Cytotoxicity(ADCC)

Neutralization

Opsonization Macrophage Extracellular bacteria Opsonization Ingestion by macrophage Digestion in lysosome

Complement Activation C2 C4 C1 Digestion in lysosome Bacteria in plasma C1 C4 C2 Complement activation Lysis and ingestion

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

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

scFv (single chain V region antibody)

Fv (Variable region fragment)

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Immunoglobulin genes