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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
2

Immune serum 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 Chains Disulfide bonds

Carbohydrate

CL VL CH1 VH CH2
Hinge Region

CH3

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
S S

Fab

Light chain C domains or

S S S S

Heavy chain C domains , , , , or Pepsin cleavage sites Papain cleavage sites

F(ab)2 - 1 x (Fab)2 & 1 x Fc - 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 F(ab`)2 No Fc Recovery, Digested Entirely

Pepsin Digestion

Immunoglobulin Fragments: Structure/Function Relationships

Fab

Papai n

Ag binding Valence = 1 Specificty determined by VH and VL


Fc Fa b

Fc Effector functions

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 s


Hinge

Elbow

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
CH2

The hinge region is replaced by 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


S S S S ss J S S

IgA and pIgR are transported to the apical surface in vesicles

S S S S

s s

S S S S

Epithelial cell

S S

J ss

S S

pIgR & IgA are internalised

S S

S S

B cells located in the submucosa produce dimeric IgA

Polymeric Ig receptors are expressed on the basolateral surface of epithelial cells to capture IgA produced in the mucosa

S S S S S S

Stalk of the pIgR is degraded to release IgA containing part of the pIgR - the secretory component
ss J S S S S S S S S ss J S S S S

Antibody Classes And Biological Activities

IgE

Very low serum concentration, 0.3g/mL Participate in immediate hypersensitivities reations. Ex. Asthma, anaphylaxis, hives

Binds Mast Cells and Blood Basophils thru FcR 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, ~30g/mL

Development of B cell

ANTIBODY: CLASSES Selected properties of human immunoglobulins


IgG Heavy chain symbol Mean serum conc. (mg/ml) Serum halflife (days) Activates complemen t Placental transfer IgA IgM IgE IgD

0.5 - 10

0.05- 3

1.5

0.0005

0.03

21 +

7 -

7 ++

2 -

2 -

Mononuclea r cells and neutrophils -

Mast cells and basophils -

Cell binding Mononuclear via F. cells and receptors neutrophils

Monoclonal antibody production

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