immunoglobulins structure and function by eisa salehi phd department of immunology
TRANSCRIPT
ImmunoglobulinsStructure and Function
By
Eisa Salehi PhD
Department of Immunology
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
Basic Immunoglobulin Structure
Immunoglobulins - heterogeneous
Myeloma proteins - homogeneous immunoglobulins
Immunoglobulin vs. Antibody
Immunoglobulin Structure
Heavy & Light Chains Disulfide bonds
Inter-chain Intra-chain
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
Immunoglobulin Structure
Variable & Constant Regions VL & CL
VH & CH
Hinge Region
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
Immunoglobulin Structure
Domains VL & CL
VH & CH1 - CH3 (or CH4)
Oligosaccharides
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
Immunoglobulin Fragments: Structure/Function Relationships
Fab Ag binding Valence = 1 Specificty
determined by VH and VL
Papain
Fc
Fab
Fc Effector functions
Immunoglobulin Fragments: Structure/Function Relationships
Fab Ag binding
Fc Effector functions
F(ab’)2
Pepsin
Fc Peptides
F(ab’)2
Immunoglobulin Fragments: Structure/Function Relationships
Ag Binding
Complement Binding Site
Placental Transfer
Binding to Fc Receptors
Structure of the Variable Region
Hypervariable (HVR) or complimentarity determining regions (CDR) Framework regions
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 (α 2) heavy chains
Human ImmunoglobulinLight Chain Types
Kappa (κ) Lambda (λ)
Human Immunoglobulin Light Chain Subtypes
Lambda light chains Lambda 1 (λ1) Lambda 2 (λ 2) Lambda 3 (λ 3) Lambda 4 (λ 4)
IgG moleculeدهد نمي تراش را ها صخره چكش
بلكهدهد مي شكل بدان آوازش و رقص و طراوات با آب
IgG
Structure Monomer (7S)
IgG1, IgG2 and IgG4 IgG3
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
IgM
Structure Pentamer (19S) Extra domain (CH4) J chain
Cμ4
J Chain
IgM
Structure Properties
3rd highest serum Ig First Ig made by fetus and B cells Fixes complement
Fixation of C1 by IgG and IgM Abs
C1r C1s
C1qC1r C1s
C1q
No activation Activation
IgM
Structure Properties
3rd highest serum Ig First Ig made by fetus
and B cells Fixes complement
Tail Piece
Agglutinating Ig Binds to Fc receptors B cell surface Ig
B Cell Antigen Receptor (BcR)
Ig- αIg- α Ig- βIg-β
IgA
Structure Serum - monomer Secretions (sIgA)
Dimer (11S) J chain Secretory
component
J ChainSecretory Piece
Origin of Secretory Component of sIgA
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 Monomer Tail piece
Tail Piece
IgD
Structure Properties
4th highest serum Ig B cell surface Ig Does not bind complement
IgE
Structure Monomer Extra domain (CH4)
Cε4
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
Immunoglobulin:Isotypes, Allotypes and Idiotypes
Human IgM
antiserum Reacts withIgM, IgG, IgA, IgD, IgE
React with IgG, IgA, IgD and IgE
Absorbed antiserum Reacts only with IgM
Recognizes determinantsspecific for μ heavy chains
(isotypes)
Immunoglobulin Isotypes
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Immunoglobulin Isotypes
Definition - Antigenic determinants that characterize the classes and subclasses of heavy chains and types and subtypes of light chains
Immunoglobulin Isotypes
Occurrence Importance
Ig levels B cell tumors Immunodeficiencies
• Definition
• Location
IgM (kappa)
حسن
IgG1 (kappa)
حسن
Immunoglobulin Allotypes
• Definition - Antigenic determinants specified by allelic forms of the Ig genes
• Location
• Occurrence
– Source of anti-allotypic Abs
IgG1 (kappa)
نقی
IgG1 (kappa)
حسن
Human Immunoglobulin Allotypes
• Nomenclature– G1m(3)– Km(1)
Chain Domain Allotype Amino Acid
Position
CH1 G1m(f) = (3) Arg 214
CH1 G1m(z) = (17) Lys 214
IgG1
CH3 G1m(a) = (1) Arg, Asp, Glu, Leu
355-358
CL Km(1) Val, Leu 153, 191 κlight chain
CL Km(3) Ala, Val 153, 191
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
Chain Domain Allotype Amino Acid
Position
CH1 G1m(f) = (3) Arg 214
CH1 G1m(z) = (17) Lys 214
IgG1
CH3 G1m(a) = (1) Arg, Asp, Glu, Leu
355-358
CL Km(1) Val, Leu 153, 191 κlight chain
CL Km(3) Ala, Val 153, 191
Chain Domain Allotype Amino Acid
Position
CH1 G1m(f) = (3) Arg 214
CH1 G1m(z) = (17) Lys 214
IgG1
CH3 G1m(a) = (1) Arg, Asp, Glu, Leu
355-358
CL Km(1) Val, Leu 153, 191 κlight chain
CL Km(3) Ala, Val 153, 191
Genetics (pseudoalleles) Co-dominant
G1m(17) G1m(1)
214 355-358
Human Immunoglobulin Allotypes
Immunoglobulin Allotypes
Definition Location Occurrence Importance
Monitoring bone marrow grafts Forensic medicine Paternity testing
Immunoglobulin Idiotypes
Definition - Unique antigenic determinants present on individual antibody molecules or on molecules of identical specificity
DNP-BSAStrain A Mouse
Anti-DNP Ab
Purifiedanti-DNP Ab
Strain A Mouse
Ab againstcombining site of anti-DNP Ab
Immunoglobulin Idiotypes
Antigenic determinants created by the HVR = Idiotypes
Immunoglobulin Idiotypes
Definition Location
IgG1 (kappa)
نقیanti-B
IgG1 (kappa)
نقیanti-A
Immunoglobulin Idiotypes
Definition Location Importance
V region marker Regulation of immune responses
Ag Id anti-Id
+
-
anti-anti-Id
+
-
Regulation by Id/anti-Id
Immunoglobulin Idiotypes
Definition Location Importance
V region marker Regulation of immune responses Vaccines
Ag Id anti-Id
+
-
Anti-Idiotype Vaccines
Ag Id anti-Id
+
Immunoglobulin Idiotypes
Definition Location Importance
V region marker Regulation of immune responses Vaccines Treatment of B cell tumors (T cell)
Immunoglobulin Superfamily
General Functions of Immunoglobulins
Effector functions Fixation of complement Binding to various cells
(Usually require Ag binding)
• Ag binding– Can result in protection– Valency
General Functions of
Immunoglobulins
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