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Immunoglobulins Structure and Function. By Eisa Salehi PhD Department of Immunology. -. +. albumin. Amount of protein. globulins. γ. β. α 1. α 2. Immune serum. Ag adsorbed serum. Mobility. Immunoglobulins:Structure and Function.

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immunoglobulins structure and function

ImmunoglobulinsStructure and Function

By

Eisa Salehi PhD

Department of Immunology

immunoglobulins structure and function1

-

+

albumin

Amount of protein

globulins

γ

β

α1

α2

Immune serum

Ag adsorbed serum

Mobility

Immunoglobulins:Structure and Function
  • Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies
basic immunoglobulin structure
Basic Immunoglobulin Structure
  • Immunoglobulins - heterogeneous
  • Myeloma proteins - homogeneous immunoglobulins
  • Immunoglobulin vs. Antibody
immunoglobulin structure

Disulfide bond

Carbohydrate

CL

VL

CH2

CH3

CH1

Hinge Region

VH

Immunoglobulin Structure
  • Heavy & Light Chains
  • Disulfide bonds
    • Inter-chain
    • Intra-chain
immunoglobulin structure1

Disulfide bond

Carbohydrate

CL

VL

CH2

CH3

CH1

Hinge Region

VH

Immunoglobulin Structure
  • Variable & Constant Regions
    • VL & CL
    • VH & CH
  • Hinge Region
immunoglobulin structure2

Disulfide bond

Carbohydrate

CL

VL

CH2

CH3

CH1

Hinge Region

VH

Immunoglobulin Structure
  • Domains
    • VL & CL
    • VH & CH1 - CH3 (or CH4)
  • Oligosaccharides
immunoglobulin fragments structure function relationships

Papain

Fc

Fab

Immunoglobulin Fragments: Structure/Function Relationships
  • Fab
    • Ag binding
    • Valence = 1
    • Specificty determined by VH and VL
  • Fc
    • Effector functions
immunoglobulin fragments structure function relationships1

Pepsin

Fc Peptides

F(ab’)2

Immunoglobulin Fragments: Structure/Function Relationships
  • Fab
    • Ag binding
  • Fc
    • Effector functions
  • F(ab’)2
immunoglobulin fragments structure function relationships2

Ag Binding

Complement Binding Site

Binding to Fc Receptors

Placental Transfer

Immunoglobulin Fragments: Structure/Function Relationships
structure of the variable region
Structure of the Variable Region
  • Hypervariable (HVR) or complimentarity determining regions (CDR)
  • Framework regions
human immunoglobulin classes
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
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 (α 2) heavy chains
human immunoglobulin light chain subtypes
Human Immunoglobulin Light Chain Subtypes
  • Lambda light chains
    • Lambda 1 (λ1)
    • Lambda 2 (λ 2)
    • Lambda 3 (λ 3)
    • Lambda 4 (λ 4)
igg molecule

IgG moleculeچكش صخره ها را تراش نمي دهد بلكه آب با طراوات و رقص و آوازش بدان شكل مي دهد

slide17

IgG1, IgG2 and IgG4

IgG3

IgG
  • Structure
    • Monomer (7S)
slide18
IgG
  • Structure
  • Properties
    • Major serum Ig
    • Major Ig in extravascular spaces
    • Placental transfer – Does not require Ag binding ( IgG2)
    • Fixes complement ( IgG4)
    • Binds to Fc receptors ( IgG2, IgG4)
      • Phagocytes - opsonization
      • K cells - ADCC
slide19

J Chain

Cμ4

IgM
  • Structure
    • Pentamer (19S)
    • Extra domain (CH4)
    • J chain
slide20
IgM
  • Structure
  • Properties
    • 3rd highest serum Ig
    • First Ig made by fetus and B cells
    • Fixes complement
slide21

C1r

C1r

C1s

C1s

C1q

C1q

Fixation of C1 by IgG and IgM Abs

No activation

Activation

slide22

Tail Piece

IgM
  • Structure
  • Properties
    • 3rd highest serum Ig
    • First Ig made by fetus and B cells
    • Fixes complement
  • Agglutinating Ig
  • Binds to Fc receptors
  • B cell surface Ig
slide24

Secretory Piece

J Chain

IgA
  • Structure
    • Serum - monomer
    • Secretions (sIgA)
      • Dimer (11S)
      • J chain
      • Secretory component
slide26
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
slide27

Tail Piece

IgD
  • Structure
    • Monomer
    • Tail piece
slide28
IgD
  • Structure
  • Properties
    • 4th highest serum Ig
    • B cell surface Ig
    • Does not bind complement
slide29

Cε4

IgE
  • Structure
    • Monomer
    • Extra domain (CH4)
slide30
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
slide35

Immunoglobulin Isotypes

Human IgM

Reacts with

IgM, IgG, IgA, IgD, IgE

??

antiserum

React with IgG, IgA, IgD and IgE

??

Absorbed antiserum

Reacts only with IgM

Recognizes determinants

specific for μ heavy chains

(isotypes)

??

immunoglobulin isotypes
Immunoglobulin Isotypes
  • Definition - Antigenic determinants that characterize the classes and subclasses of heavy chains and types and subtypes of light chains
immunoglobulin isotypes1

IgG1 (kappa)

حسن

IgM (kappa)

حسن

Immunoglobulin Isotypes
  • Occurrence
  • Importance
    • Ig levels
    • B cell tumors
    • Immunodeficiencies
  • Definition
  • Location
immunoglobulin allotypes

IgG1 (kappa)

حسن

IgG1 (kappa)

نقی

Immunoglobulin Allotypes
  • Definition - Antigenic determinants specified
  • by allelic forms of the Ig genes
  • Source of anti-allotypic Abs
  • Location
  • Occurrence
human immunoglobulin allotypes
Human Immunoglobulin Allotypes
  • Nomenclature
    • G1m(3)
    • Km(1)
human immunoglobulin allotypes1
Human Immunoglobulin Allotypes
  • Genetics (alleles)
    • Co-dominant
    • autosomal genes

Km(1)/Km(3) X Km(1)/Km(1)

Km(1)/Km(1) and Km(1)/Km(3)

  • Allelic exclusion
human immunoglobulin allotypes2
Human Immunoglobulin Allotypes
  • Genetics (pseudoalleles)
    • Co-dominant

G1m(17)

G1m(1)

214

355-358

immunoglobulin allotypes1
Immunoglobulin Allotypes
  • Definition
  • Location
  • Occurrence
  • Importance
    • Monitoring bone marrow grafts
    • Forensic medicine
    • Paternity testing
immunoglobulin idiotypes
Immunoglobulin Idiotypes
  • Definition - Unique antigenic determinants present on individual antibody molecules or on molecules of identical specificity
slide44

Immunoglobulin Idiotypes

Strain A

Mouse

Anti-DNP Ab

DNP-BSA

Ab against

combining site of

anti-DNP Ab

Strain A

Mouse

Purified

anti-DNP Ab

Antigenic determinants created by the HVR = Idiotypes

immunoglobulin idiotypes1
Immunoglobulin Idiotypes
  • Definition
  • Location

IgG1 (kappa)

نقی

anti-A

IgG1 (kappa)

نقی

anti-B

immunoglobulin idiotypes2
Immunoglobulin Idiotypes
  • Definition
  • Location
  • Importance
    • V region marker
    • Regulation of immune responses
slide47

Regulation by Id/anti-Id

+

+

Ag

Id

anti-Id

anti-anti-Id

-

-

immunoglobulin idiotypes3
Immunoglobulin Idiotypes
  • Definition
  • Location
  • Importance
    • V region marker
    • Regulation of immune responses
    • Vaccines
slide50

+

+

Ag

Id

anti-Id

Ag

Id

anti-Id

-

Anti-Idiotype Vaccines

immunoglobulin idiotypes4
Immunoglobulin Idiotypes
  • Definition
  • Location
  • Importance
    • V region marker
    • Regulation of immune responses
    • Vaccines
    • Treatment of B cell tumors (T cell)
general functions of immunoglobulins
General Functions of Immunoglobulins
  • Effector functions
    • Fixation of complement
    • Binding to various cells
  • Ag binding
    • Can result in protection
    • Valency

(Usually require Ag binding)

slide62

آنچه سبب غرق شدن مي گردد فرو رفتن در آب نيست بلكه ماندن زير آب است