Immunoglobulins: Structure and Function

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ImmunoglobulinsStructure 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 requires Ag binding

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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

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Immunoglobulins (Ig) are
glycoproteins made up of light (L) and heavy(H)
polypeptide chains. The simplest
antibody molecule has a Y shape and
consists of four polypeptide chainstwo H chains
and two L chains. The four chains are linked by
disulfide bonds.
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Immunoglobulin Structure

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

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H chains are distinct for each Of
the five Ig classes or isotypes and are
designated ? a µd e for the respective
classes of Ig, namely IgG IgA IgM
IgD IgE.
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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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L chains are one of two types Designated
? and ? and only one type is found in Ig.
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Human ImmunoglobulinLight Chain Types

• Kappa (?)
• Lambda (?)

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L and H chains are subdivided into
variable and constant regions.The regions are
composed of three-dimensionally folded,
repeating segments called domains. An L chain
consists of one variable (VL) and one constant
(CL) domain.Most H chains consist of one
variable (VH) and three constant(CH)
domains.(IgG and IgA have three CH
domains,whereas IgM and IgE have four.)
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Immunoglobulin Structure

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

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The various regions are responsible
for antigenbinding ,whereas the constant
regions are responsible for various
biologic functions eg, complement
activation and binding to cell surface
receptors.
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The variable regions of both L and H
chains have three extremely variable
(hypervariable) amino acid sequence at
the amino- terminal end that form the
antigen- binding site.
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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
• Specificty 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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IgG

• Structure
• Monomer (7S)

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IgG

• Structure
• Properties
• Major serum Ig
• Major Ig in extravascular spaces
• The only antibody to cross the placental
• Fixes complement
• Binds to Fc receptors
• Phagocytes - opsonization
• NK cells ADCC
• Binds to SPA

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IgM

• Structure
• Pentamer (19S)
• composed 5 H2L2 units plus one
  molecule of
• J chain
• Extra domain (CH4)
• J chain

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Fixation of C1 by IgG and IgM Abs
No activation
Activation
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IgM

• Structure
• Properties
• 3rd highest serum Ig
• First Ig made by fetus and B cells
• Produced early in the primary response
• The most efficient Ig
• Fixes complement

Agglutinating Ig Binds to Fc receptors B cell
surface Ig
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B Cell Antigen Receptor (BcR)
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IgA

• Structure
• Serum - monomer
• Secretions (sIgA)
• Dimer (11S), sIgA molecule consists of two H2L2
  units plus one molecule each of J chain and
  secretory component(SC or SP)

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Origin of sIgA The SP is a polypeptide
synthesized by epithelial cells that provides for
IgA passage to the mucosal surface. It also
protests IgA from being degraded in the
intestinal tract.
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IgA

• Properties
• 2nd highest serum Ig
• Major secretory Ig ( saliva, tears, respiratory,
  intestinal, and genital
• tract secretions.)
• Does not fix complement unless aggregated
• Binds to Fc receptors on some cells

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IgD

• Structure
• Monomer
• 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)

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IgE

• Structure
• Properties
• Least common serum Ig
• Allergic reactions
• Parasitic infections
• Does not fix complement