immunology (elective) mlim-101
DESCRIPTION
Immunology (elective) MLIM-101. Prepared by: Dr. Mohamed S. Abdel- Latif. Immunoglobulins : Structure and Function. Learning Outcome:. At this time you should know the following: 1. To discuss the general properties of all immunoglobulins - PowerPoint PPT PresentationTRANSCRIPT
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Immunology Immunology (elective)(elective)
MLIM-101 MLIM-101
Prepared by: Prepared by:
Dr. Mohamed S. Dr. Mohamed S. Abdel-LatifAbdel-Latif
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Immunoglobulins:Immunoglobulins:Structure and Structure and
FunctionFunction
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Learning Outcome:Learning Outcome:
At this time you should know the following:At this time you should know the following:
1. To discuss the general properties of all immunoglobulins1. To discuss the general properties of all immunoglobulins2. To describe the basic structure of immunoglobulins2. To describe the basic structure of immunoglobulins3. To relate immunoglobulin structure with function3. To relate immunoglobulin structure with function4. To define immunoglobulin hypervariable and framework 4. To define immunoglobulin hypervariable and framework regionsregions5. To define immunoglobulin classes and subclasses, types 5. To define immunoglobulin classes and subclasses, types and subtypesand subtypes6. To describe the structures and properties of 6. To describe the structures and properties of immunoglobulin classesimmunoglobulin classes
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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
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General Functions of Immunoglobulins
• Effector functions – Fixation of complement– Binding to various cells
(Usually require Ag binding)
• Ag binding– Can result in protection– Valency
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Basic Immunoglobulin Structure
• Immunoglobulins - heterogeneous
• Myeloma proteins - homogeneous immunoglobulins
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Immunoglobulin Structure
• Heavy & Light Chains
• Disulfide bonds– Inter-chain– Intra-chain
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
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Immunoglobulin Structure
• Variable & Constant Regions– VL & CL
– VH & CH
• Hinge RegionCH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
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Immunoglobulin Structure
• Domains– VL & CL
– VH & CH1 - CH3 (or CH4)
• Oligosaccharides CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
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IgG molecule
Used with permission from: Dr. Mike Clark, Immunology Division, Department of Pathology Cambridge University, Cambridge, England
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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
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Immunoglobulin Fragments: Structure/Function Relationships
• Fab– Ag binding– Valence = 1– Specificty
determined by VH and VL
Papain
Fc
Fab
• Fc– Effector functions
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Immunoglobulin Fragments: Structure/Function Relationships
Ag Binding
Complement Binding Site
Placental Transfer
Binding to Fc Receptors
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Immunoglobulin Fragments: Structure/Function Relationships
• Fab– Ag binding
• Fc– Effector functions
• F(ab’)2
Pepsin
Fc Peptides
F(ab’)2
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Human Immunoglobulin Classes
• IgG - Gamma () heavy chains
• IgM - Mu () heavy chains
• IgA - Alpha () heavy chains
• IgD - Delta () heavy chains
• IgE - Epsilon () heavy chains
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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
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Human ImmunoglobulinLight Chain Types
• Kappa ()
• Lambda ()
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Human ImmunoglobulinLight Chain Subtypes
• Lambda light chains– Lambda 1 (1)– Lambda 2 (2)– Lambda 3 (3) – Lambda 4 (4)
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Immunoglobulins
• Nomenclature– IgM (kappa)– IgA1(lambda 2)– IgG
• Heterogeneity
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IgG
• Structure– Monomer (7S)
IgG1, IgG2 and IgG4 IgG3
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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
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IgM
• Structure– Pentamer (19S)
– Extra domain (CH4)
– J chainC4
J Chain
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IgM
• Structure
• Properties– 3rd highest serum Ig– First Ig made by fetus
and B cells– Fixes complement
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Fixation of C1 by IgG and IgM Abs
C1r C1s
C1qC1r C1s
C1q
No activation Activation
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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
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B Cell Antigen Receptor (BcR)
Ig-Ig- Ig-Ig-
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IgA
• Structure– Serum - monomer– Secretions (sIgA)
• Dimer (11S)
• J chain
• Secretory component
J ChainSecretory Piece
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Origin of Secretory Component of sIgA
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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
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IgD
• Structure– Monomer– Tail piece
Tail Piece
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IgD
• Structure
• Properties– 4th highest serum Ig– B cell surface Ig– Does not bind complement
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IgE
• Structure– Monomer
– Extra domain (CH4)
C4
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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
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Assignment:
As a part of the semester activity, group of students are selected every week to prepare a short seminar about his/her point of interest in one of the lecture topics. That to be discussed and evaluated during the next lecture.