ImmunoglobulinStructure and Function

By

Associate Lecturer Mortadha H AL-Hussainy

Faculty of Veterinary Medicine

Kufa University

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.

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

Am

oun

t of

pro

tein

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

Basic Immunoglobulin Structure

• Immunoglobulins - heterogeneous

• Myeloma proteins - homogeneous immunoglobulins

Two Forms of Immunoglobulin

Membrane-bound receptor Soluble antibody

Immunoglobulin Structure

• Variable(V) & Constant (C) Regions– VL & CL

– VH & CH

• Hinge Region

CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond

Structural Regions

• hypervariable region

• also called

Complementarity Determining Regions(CDRs),

超变区超变区（（ hyper-variable region, HVRhyper-variable region, HVR)),, 又称又称互补决互补决定定区区 (complementary determining region, CD(complementary determining region, CDRR ））

IgG molecule

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

Enzymatic Digestion Products of Immunoglobulins

Immunoglobulin Fragments: Structure/Function Relationships

• Fab– Ag binding– Valence = 1– Specificity

determined by VH and VL

Papain

Fc

Fab

• Fc ( crystallizable)– Effector functions

Domains of Immunoglobulin

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.

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

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.

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

Five Classes of Immunoglobulin

• IgG has a family of subclass, IgG1, IgG2, IgG3,

IgG4(cattle has no)

• IgA is divided into two subclasses, IgA1 and

IgA2(sheep).

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

B Cell Antigen Receptor (BCR)

Ig-αIg-β Ig-βIg-α

IgA

• Structure– Serum - monomer– Secretions (sIgA)

• Dimer (11S)• J chain• Secretory component

J ChainSecretory Piece

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

IgD

• Structure

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

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