L5 immunoglobulins

Immunoglobulins:Structure and Function

Immunology Lecture Dr.Jassim M.Abdo



• Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies

Immune serumAg adsorbed serum

α1 α2 β γ

+ -albumin

globulins

Mobility

Am

ount

of p

rote

in

General Functions of Immunoglobulins

• Effector functions – Fixation of complement– Binding to various cells

(Usually require Ag binding)

• Ag binding– Can result in protection– Valence

Basic Immunoglobulin Structure

• Immunoglobulins - heterogeneous

• Myeloma proteins - homogeneous immunoglobulins

Immunoglobulin Structure

• Heavy & Light Chains

• Disulfide bonds– Inter-chain– Intra-chain

CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond


• Variable & Constant Regions– VL & CL

– VH & CH

• Hinge Region CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond


• Domains– VL & CL

– VH & CH1 - CH3 (or CH4)

• Oligosaccharides CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond

Structure of the Variable Region• Hypervariable (HVR) or complimentarity

determining regions (CDR) HVR3

FR1 FR2 FR3 FR4

HVR1HVR2

Varia

bilit

y In

dex

25 7550 100Amino acid residue

150

100

50

0

• Framework regions

Immunoglobulin Fragments: Structure/Function Relationships

• Fab– Ag binding– Valence = 1– Specificity

determined by VH and VL

Papain

Fc

Fab

• Fc– Effector functions


Ag Binding

Complement Binding Site

Placental Transfer

Binding to Fc Receptors


• Fab– Ag binding

• Fc– Effector functions

• F(ab’)2

Pepsin

Fc Peptides

F(ab’)2

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

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

Human ImmunoglobulinLight Chain Types

• Kappa (κ)• Lambda (λ)

Immunoglobulins• Nomenclature

– IgM (kappa)– IgA1(lambda 2)– IgG

• Heterogeneity

IgG• Structure• Properties

– Major serum Ig (systemic immunity)– Major Ig in extravascular spaces– Placental transfer – Does not require Ag

binding– Fixes complement(IgG Ab can activate the

clasical complement pathway . – Binds to Fc receptors

• Phagocytes - opsonization• K cells - ADCC

IgG• Typical BCR structure with two identical light chains and two identical

γ heavy chains.• It is made and secreted by plasma cells in the spleen, lymph node ,nd

bone marrow.• Highest concentration in the Blood plays a major role in the

antibody –mediated defense mechanism .• Molecular weight 180 kD

IgG

• Structure– Monomer (7S)

CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond

IgM• Produced by plasma cells in the spleen ,lymph node ,and bone

marrow.• It is second highest concentration in the most mammalian serum .• Consist from 5 180 kDa subunit linked by disulfide bonds in circular, j

chains joint two of the unit to complete the circle .• It is the major immunoglobulin produced during a primary immune

response ,it also produced in secondary response but in small amount .• it is rarely to inter tissue site because of their very large size

IgM

• Structure– Pentamer (19S)– Extra domain (CH4)– J chain

Cµ4

J Chain

IgM• Structure• Properties

– First Ig made by fetus and B cells– Fixes complement– More efficient than IgG at a complement

activation ,opsonization, neutralization of viruses and agglutination.

IgM

• Structure• Properties

– First Ig made by fetus and B cells

– Fixes complement

Tail Piece

– Agglutinating Ig– Binds to Fc receptors– B cell surface Ig

IgA• Molecular weight 360 kDa.• It can act in inside cells• Synthesized and Secreted by plasma cells in the intestinal submucosa.• IgA bind to glycoprotein receptors (pIgR) to make complex in the Basel surface of

enterocyte .

IgA

IgA• It made in the walls of the intestine ,respiratory

tract ,urinary system , skin and mammary gland

IgA• Structure

– Serum - monomer– Secretions (sIgA)

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

J ChainSecretory Piece

IgA• Structure• Properties

– 3nd highest serum Ig– Does not fix complement (unless aggregated)– Binds to Fc receptors on some cells

IgE• Structure

– Monomer– Extra domain (CH4)

Cε4

IgE• Structure• 200 kDa• Properties

– Least common serum Ig(low conc in serum thefore can’t bined to Ag• Binds to basophils and mast cells (Does not require

Ag binding)– Allergic reactions(mediated Type I

hypersensitivity reaction).– Short life 2-3 days.– Parasitic infections (Helminths)

• Binds to Fc receptor on eosinophils– Does not fix complement

IgD

• Structure– Monomer– Tail piece– 180 kDa

Tail Piece

IgD

• IgD has been not detected in in all mammals.• Found in rodents, cattle ,sheep and pigs and

probably present in dog.• It has been not detected in horses,rabbits.• It has been identified in certain

fish(catfish,salmon,cod) but not been found in chickens.

• Like IgE,IgD. Is destroyed by mild heat treatment.• IgD doesn't found in serum but in plasma .

IgD• Structure• Properties

– 4th highest serum Ig– Mainly attached B cell(B cell surface Ig)– Does not bind complement

IMMUNOGLOBULIN VARIANTS isotype, Allotypes Idiotypes

• Subclasses: immunoglobuline classes consist of a mixture of molecules with structurally different heavy chains.

• Allotypes: inherited sequence variation in in heavy chain genes (inherited variation in in immunoglobulin amino acid sequences ) in individual animal .

Homozygous: individual have the same allotype in all immunoglobulin in a class.Hetrozygous halve of immunoglobulin molecules will be of one allotype and half will be the other.

Idiotypes • Variation in the amino acid in sequence within the variable domain in light and heavy

chains.

L5 immunoglobulins

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