: Immunoglobulins: Structure and Function

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????????? ???????? ??????? ????????Immunoglobuli
nsStructure and Function
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ImmunoglobulinsStructure and Function

• ?????
• Definition Glycoprotein molecules that are
  produced by plasma cells in response to an
  immunogen and which function as antibodies

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General Functions of Immunoglobulins

• Ag binding ???????? ?????????
• Can result in protection ?????
• Valency ???? ???????

??????? ???????

• Effector functions
• Fixation of complement ????? ??????
• Binding to various cells ???????? ????????

(Usually require Ag binding)
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???????? ????????Basic Immunoglobulin Structure

• Immunoglobulins - heterogeneous
• Polyclonal
  antibody
• Myeloma proteins - homogeneous immunoglobulins
• Monoclonal
  antibody

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???????Immunoglobulin Structure
???????
???????

• Heavy Light Chains ?????
• Disulfide bonds ????? ?????????
• Inter-chain
• Intra-chain

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????? ???????Immunoglobulin Structure

• Variable Constant Regions
• VL CL
• VH CH
• Hinge Region
• ????? ???????

??????? ???????? ????????
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Immunoglobulin Structure

• Domains ?????????
• VL CL
• VH CH1 - CH3 (or CH4)
• Oligosaccharides
• ??????? ??????? ????????? CDR

complimentarity determining regions (CDR)
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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)

• Framework regions

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????? ?????????? ????????Immunoglobulin
Fragments Structure/Function Relationships
??????? ??? ??????? / ???????

• Fab
• Ag binding
• Valence 1
• Specificity determined by VH and VL

• Fc
• Effector functions

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Immunoglobulin Fragments Structure/Function
Relationships
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Immunoglobulin Fragments Structure/Function
Relationships

• Fab
• Ag binding
• Fc
• Effector functions
• 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 (?) 60 ?? ???????
  
• Lambda (?) 40
• Kappa 95 ??
  ?????
• Lambda 5

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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) ????? ?????

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IgG

• Structure
• Properties
• Major serum Ig 80
• 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 chain
• S ???? ???????

?????
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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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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

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IgA

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

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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

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IgD

• Structure
• Monomer
• Tail piece

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IgD

• Structure
• Properties
• 4th highest serum Ig
• B cell surface Ig

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IgE

• Structure
• Monomer
• Extra domain (CH4)

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IgE

• Structure
• Properties
• Least common serum Ig
• Binds to basophils and mast cells (Does not
  require Ag binding)
• Allergic reactions