Immunoglobulin

Francis Ian L. Salaver, RMT

 Immunoglobulins:Structure and
Function

 Definition: Glycoprotein molecules that

are produced by plasma cells in response
to an immunogen
+ -
Amount of protein

albumin
globulins

1    Immune serum
2 Ag adsorbed serum

Mobility
 Immunoglobulin
 Element of adaptive immune mechanism
 Better known as antibody
 It recognize the foreign objects
Human Immunoglobulin Classes
 IgG - Gamma heavy chains
 IgM - Mu heavy chains
 IgA - Alpha heavy chains
 IgD - Delta heavy chains
 IgE - Epsilon heavy chains
Heavy and Light Chains
 Heavy chain
 Five Basic Sequence Patterns
 ,, , , 
 IgA, IgG, IgD, IgE and IgM

 Light chain
 Each class can have either  or  light chains
 Immunoglobulin Structure
Disulfide bond

 Heavy & Light Carbohydrate

Chains
CL
 Disulfide bonds VL

CH2 CH3
CH1
Hinge Region
VH
 Heavy chains
 The heavy chains
each have four
domains
 Variable domains
(VH)
 Constant domains
(CH1,2,3)
 Light chain
 The light chains
are constructed of
two domains
 Variable (VL)
 Constant (CL)
 Domain Structure of Immunoglobulins
Domains are folded, compact, protease resistant structures

Fc Fab

S Light chain C
S domains
 or 
S S
S S

S
S
Heavy chain C
domains
, , , , or 
F(ab)2

Pepsin cleavage sites - 1 x (Fab)2 & 1 x Fc

Papain cleavage sites - 2 x Fab 1 x Fc
 Digestion With Papain Yields
 3 Fragments
 2 identical Fab and 1 Fc
 Fab Because Fragment That is Antigen Binding
 Fc Because Found To Crystallize In Cold Storage
 Pepsin Digestion
 F(ab`)2
 No Fc Recovery, Digested Entirely
 Immunoglobulin Fragments:
Structure/Function Relationships

Papai
 Fab n

 Ag binding
 Valence = 1
 Specificty
determined by
VH and VL
Fc
•Fc
Fa
Effector functions b
 Structure of immunoglobulin
 The fragment antigen
binding (Fab fragment)
 The fragment crystallizable
region (Fc region)
 Antibodies bind to antigens
by reversible, noncovalent
interactions, including
hydrogen bonds and
charge interactions
Immunoglobulin Fragments:
Structure/Function Relationships
Ag
Binding

Complement Binding Site

Binding to Fc
Receptors
Placental
Transfer
Flexibility and
motion of
immunoglobulin Elbow
s

Hinge
Hinge Region
 Rich in proline residues (flexible)
 Hinge found in IgG, IgA and IgD
 IgM and IgE lack hinge region
 Proline residues are target for proteolytic
digestion (papain and pepsin)
 They instead have extra CH4 Domain
Structure and function of the Fc region

IgA IgD IgG

IgE IgM
The hinge region is replaced by
CH2 an additional Ig domain
Human Immunoglobulin Classes
 IgG - Gamma heavy chains
 IgM - Mu heavy chains
 IgA - Alpha heavy chains
 IgD - Delta heavy chains
 IgE - Epsilon heavy chains
Antibody Classes And Biological
Activities

 IgM
 5-10% of serum immunoglobulin
 1.5mg/mL
 MonomericIgM (also IgD) expressed on B-cells as BCR
 Pentameric version is secreted
 First Ig of primary immune response
 High valence Ig (10 theoretical), 5 empirical
 More efficient than IgG in complement activation
Development of B cell
Secreted form of IgM
(Pentameric)
First Ig in immune response
Complement Activation
Antibody Classes And Biological
Activities

 IgG
 Most abundant immunoglobin 80% of
serum Ig
 ~10mg/mL
 IgG1,2,3,4 (decreasing serum
concentration)
 IgG1, IgG3 and IgG4 cross placenta
 IgG3 Most effective complement activator
 IgG1 and IgG3 High affinity for FcR on
phagocytic cells, good for opsonization
Most abundant Immunoglobulin
Can cross placenta
Opsonization
Complement Activation
IgG subclass
Antibody Classes And Biological
Activities

 IgA
 10-15% of serum IgG
 Predominant Ig in secretions
 Milk, saliva, tears, mucus
 5-15 g of IgA released in secretions!!!!
 Serum mainly monomeric, dimeric
polymers possible not common though
 Secretions, as dimer plus secretory
component
•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.
 Secretory IgA and transcytosis
‘Stalk’ of the pIgR is degraded to release IgA
containing part of the pIgR - the secretory SS SS
ss

component S
S
J
S
S

SS SS SS SS
ss ss

S J S S J S
S S S S

IgA and pIgR

are transported Epithelial
SS SS
to the apical J
ss cell
surface in SS SS

vesicles

pIgR & IgA are Polymeric Ig receptors

S
S J S
S
internalised are expressed on the
basolateral surface of
ss
SS SS

epithelial cells to
capture IgA produced

B
B cells located in the submucosa in the mucosa
produce dimeric IgA
Antibody Classes And Biological
Activities

 IgE
 Very low serum concentration, 0.3g/mL
 Participate in immediate hypersensitivities
reations. Ex. Asthma, anaphylaxis, hives
 Binds Mast Cells and Blood Basophils
thru FcR
 Binding causes degranulation
(Histamine Release)
Cross-Linkage of Bound IgE
Antibody With Allergen Causes
Antibody Classes And Biological
Activities

 IgD
 Expressed on B-cell Surface
 IgM and IgD, Expressed on B-cell
Surface
 No known function
 Low serum concentrations, ~30g/mL
Development of B cell
ANTIBODY: CLASSES
Selected properties of human immunoglobulins
IgG IgA IgM IgE IgD
Heavy ᵞ α μ ε δ
chain
symbol
Mean 0.5 - 10 0.05- 3 1.5 0.0005 0.03
serum
conc.
(mg/ml)
Serum half- 21 7 7 2 2
life (days)
Activates + - ++ - -
complemen
t
Placental + - - - -
transfer
Cell binding Mononuclear Mononuclea - Mast cells -
via F. cells and r cells and and
receptors neutrophils neutrophils basophils
Monoclonal antibody production