immunoglobulins: structure and function. definition: glycoprotein molecules that are produced by...
Post on 19-Dec-2015
215 views
TRANSCRIPT
![Page 1: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/1.jpg)
Immunoglobulins:Structure and Function
![Page 2: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/2.jpg)
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
1 2
+ -
albumin
globulins
Mobility
Am
oun
t of
pro
tein
![Page 3: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/3.jpg)
General Functions of Immunoglobulins
• Effector functions – Fixation of complement– Binding to various cells
(Usually require Ag binding)
• Ag binding– Can result in protection– Valency
![Page 4: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/4.jpg)
Basic Immunoglobulin Structure
• Immunoglobulins - heterogeneous
• Myeloma proteins - homogeneous immunoglobulins
![Page 5: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/5.jpg)
Immunoglobulin Structure
• Heavy & Light Chains
• Disulfide bonds– Inter-chain– Intra-chain
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
![Page 6: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/6.jpg)
Immunoglobulin Structure
• Variable & Constant Regions– VL & CL
– VH & CH
• Hinge RegionCH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
![Page 7: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/7.jpg)
Immunoglobulin Structure
• Domains– VL & CL
– VH & CH1 - CH3 (or CH4)
• Oligosaccharides CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
![Page 8: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/8.jpg)
IgG molecule
Used with permission from: Dr. Mike Clark, Immunology Division, Department of Pathology Cambridge University, Cambridge, England
![Page 9: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/9.jpg)
Structure of the Variable Region
• Hypervariable (HVR) or complimentarity determining regions (CDR)
HVR3
FR1 FR2 FR3 FR4
HVR1HVR2
Var
iabi
lity
Ind
ex
25 7550 100Amino acid residue
150
100
50
0
• Framework regions
![Page 10: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/10.jpg)
Immunoglobulin Fragments: Structure/Function Relationships
• Fab– Ag binding– Valence = 1– Specificty determined
by VH and VL
Papain
Fc
Fab
• Fc– Effector functions
![Page 11: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/11.jpg)
Immunoglobulin Fragments: Structure/Function Relationships
Ag Binding
Complement Binding Site
Placental Transfer
Binding to Fc Receptors
![Page 12: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/12.jpg)
Immunoglobulin Fragments: Structure/Function Relationships
• Fab– Ag binding
• Fc– Effector functions
• F(ab’)2
Pepsin
Fc Peptides
F(ab’)2
![Page 13: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/13.jpg)
Human Immunoglobulin Classes
• IgG - Gamma () heavy chains
• IgM - Mu () heavy chains
• IgA - Alpha () heavy chains
• IgD - Delta () heavy chains
• IgE - Epsilon () heavy chains
![Page 14: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/14.jpg)
Human Immunoglobulin Subclasses
• IgG Subclasses– IgG1 - Gamma 1 (1) heavy chains– IgG2 - Gamma 2 (2) heavy chains– IgG3 - Gamma 3 (3) heavy chains– IgG4 - Gamma 4 (4) heavy chains
• IgA subclasses– IgA1 - Alpha 1 (1) heavy chains– IgA2 - Alpha 2 (2) heavy chains
![Page 15: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/15.jpg)
Human ImmunoglobulinLight Chain Types
• Kappa ()
• Lambda ()
![Page 16: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/16.jpg)
Human ImmunoglobulinLight Chain Subtypes
• Lambda light chains– Lambda 1 (1)– Lambda 2 (2)– Lambda 3 (3) – Lambda 4 (4)
![Page 17: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/17.jpg)
Immunoglobulins
• Nomenclature– IgM (kappa)– IgA1(lambda 2)– IgG
• Heterogeneity
![Page 18: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/18.jpg)
IgG
• Structure– Monomer (7S)
IgG1, IgG2 and IgG4 IgG3
![Page 19: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/19.jpg)
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
![Page 20: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/20.jpg)
IgM
• Structure– Pentamer (19S)
– Extra domain (CH4)
– J chainC4
J Chain
![Page 21: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/21.jpg)
IgM• Structure
• Properties– 3rd highest serum Ig– First Ig made by fetus
and B cells– Fixes complement
![Page 22: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/22.jpg)
Fixation of C1 by IgG and IgM Abs
C1r C1s
C1qC1r C1s
C1q
No activation Activation
![Page 23: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/23.jpg)
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
![Page 24: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/24.jpg)
B Cell Antigen Receptor (BcR)
Ig-Ig- Ig-Ig-
![Page 25: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/25.jpg)
IgA
• Structure– Serum - monomer– Secretions (sIgA)
• Dimer (11S)
• J chain
• Secretory component
J ChainSecretory Piece
![Page 26: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/26.jpg)
Origin of Secretory Component of sIgA
![Page 27: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/27.jpg)
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
![Page 28: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/28.jpg)
IgD
• Structure– Monomer– Tail piece
Tail Piece
![Page 29: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/29.jpg)
IgD
• Structure
• Properties– 4th highest serum Ig– B cell surface Ig– Does not bind complement
![Page 30: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/30.jpg)
IgE
• Structure– Monomer
– Extra domain (CH4)
C4
![Page 31: Immunoglobulins: Structure and Function. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function](https://reader035.vdocuments.us/reader035/viewer/2022062714/56649d295503460f949fe058/html5/thumbnails/31.jpg)
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