lecture on immunoglobulins
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Immunoglobulins:Structure and Function
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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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Immunoglobulin Has Two Roles
• Antigen Receptor– Recognition of and binding to antigens such as
toxins, viruses, and exposed molecules on the surface of pathogenic organisms
– V domain function
• Effector Molecule– Elimination or inactivation of the foreign antigen
or the cell that bears the antigen– C domain function
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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
The first 108 amino acids in light chains and first 118 amino acids in heavy chains constitute the variable region
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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
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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
• Fab– Ag binding
• Fc– Effector functions
• F(ab’)2
Pepsin
Fc Peptides
F(ab’)2
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Human Immunoglobulin Classes
Depending on the heavy chain make up, the
immunoglobulins are differentiated into 5 major
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 heavy chains– IgG2 - Gamma 2 heavy chains– IgG3 - Gamma 3 heavy chains– IgG4 - Gamma 4 heavy chains
• IgA subclasses– IgA1 - Alpha 1 heavy chains– IgA2 - Alpha 2 heavy chains
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Human ImmunoglobulinLight Chain Types
• Kappa
• Lambda
In human beings, 60% light chains are of
Kappa variety and 40% are of Lamda type
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Human ImmunoglobulinLight Chain Subtypes
• Lambda light chains– Lambda 1 – Lambda 2 – Lambda 3 – Lambda 4
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IgG
• Structure– Monomer (7S)
IgG1, IgG2 and IgG4 IgG3
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IgG Predominant Ig of blood (75-
80%) 1 unit, smallest Longest half-life Antibody seen in secondary
immnue response Passive transfer Crosses placental barrier – Rh
iso-immunization Agglutination Opsonization Complement Actn.
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IgM
• Structure
– Pentamer (19S)
– Extra domain (CH4)
– J chain C4
J Chain
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IgM It can combine with 5 antigens
simultaneously 3rd highest serum Ig First Ig made by fetus and B
cells Major Ig of primary response No hinge region Natural antibodies are IgM in
nature It cannot cross the placenta Agglutination, C’ act.
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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 Serum-monomer 2nd highest serum Ig 2 units
J chain secretory component produced by
epithelial cells Major secretory Ig (Mucosal or Local
Immunity)– Tears, saliva, gastric and pulmonary
secretions Prevents attachment & penetration of
microorganisms Does not fix complement (unless
aggregated)
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IgD
• Structure– Monomer– Tail piece
Tail Piece
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IgD
1 unit
4th highest serum Ig
Long hinge region.
Found as membrane receptor on early B cells.
Does not bind complement
Not in all species.
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IgE
• Structure– Monomer
– Extra domain (CH4)
C4
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IgE 1 unit Least common serum Ig Extra CH domain binds IgE specific receptors on
basophils and mast cells. Ag binding induces degranulation. Parasitic immunity
Binds to Fc receptor on eosinophils
Type I Hypersensitivity Allergy
Does not fix complement
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IgE-Induced Degranulation of Mast CellsIn Allergy
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Clinical aspect
• Paraproteinemias
– Multiple myeloma
– Bence-Jones proteinuria
– Waldenstrom’s macroglobulinemia
– Hyper gamma globulinemia
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Multiple myeloma
• When Ig secreting cells are transformed into malignant cells, one clone alone is enormously proliferated
• This is seen in electrophoresis as the myeloma band or monoclonal band or M band
• It is characterised by paraproteinemia, anemia, lytic bone lesions and proteinuria
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• Bone marrow examination reveals large number of malignant plasma cells
• Spontaneous pathological fracture of weight bearing bones, ribs and vertebrae may occur
• X-ray shows punched out osteolytic lesions
• Hypercalcemia and hypercalciuria
• Raised beta-2 microglobin
• Immunity is depressed
• Prognosis is good
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Bence-Jones proteinuria
• Seen in 20% of patients with multiple myeloma
• Monoclonal light chains are excreted in urine
• They precipitate when heated between 45ºC and 60ºC; but redissolving at higher than 80ºC and lower than 45ºC
• Bradshaw’s test