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IMMUNOGLOBULIN

IgM, IgE, IgD

Rhea Ong, DMD

objectives
To discuss function To discuss structure to know classification of immunoglobulin

terms
Immunoglobulin Fab

Immunoglobulin
TWO Roles
plasma membrane bound antigen receptors on the surface of a B-cell as antibodies free in cellular fluids

*antibody function is intimately related to its structure

GENERAL FUNCTIONS OF IMMUNOGLOBULINS


A. Antigen binding B. Effector Functions 1.Fixation of complement 2.Binding to various cell types

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AB
- The valency of antibody refers to the number of antigenic determinants that an individual antibody molecule can bind
EF - biological effects are a consequence of secondary "effector functions" of antibodies *binding of an antibody to an antigen has no direct biological effect *usually the ability to carry out a particular effector function requires that the antibody bind to its antigen

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immunoglobulins mediate a effector functions Not every immunoglobulin will mediate all effector functions

Basic Immunoglobulin Structure


1. Four polypeptide chains: two "light" chains two "heavy" chains 2. Disulfide (-S-S-) bonds 3. Hinge Region

LIGHT CHAIN
220 amino acids

Constant 110 amino acids


variable 110 amino acids
Hypervariable* Framework region Framework region

HEAVY CHAIN
440-550 amino acids

Constant 110 amino acids variable 340-440 amino acids


Hypervariable* Framework region

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heavy chain an immunoglobulin determines the immunoglobulin "isotype - classification IgA IgG IgM IgE IgD

constant variable
Hypervariable Framework region

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Hypervariable Epitope is found

IMMUNOGLOBULIN FRAGMENTS: STRUCTURE/FUNCTION RELATIONSHIPS

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Fab

- The combining site of the antibody is created by both VH and VL


Fc - contains the remainder of the two heavy chains each containing a CH2 and CH3 domain

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Functions are either
Independent of the particular class Dependent of the particular class

GENERATION OF ANTIBODY DIVERSITY


Multiple genes in the germ line DNA Variable recombination during differentiaion of the germ line cells into B-cells Mutations during differentiaion of the germ line cells into B-cells

Multiple genes in the germ line DNA

Variable recombination

Mutations

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The immune System has the capacity to recognize and respond to about 10,000,000

Heavy Chain (VDJ)- 200 X 12 X 4 = 9600 Light Chain (VJ)- 200 X 5 = 1000

9,600,000

IMUNNOGLOBULIN PRODUCTION
Rearrangement Recombination Mutation

DIFFERENT TYPES OF IMMUNOGLOBULIN

IgM IgE IgD

IgM
Heavy chain: Mu Its mean concentration in serum is 0.4-2.5 mg/mL with a half-life of 7 days first immunoglobulin to be generated by a neonate. It is also the EARLIEST immunoglobulin to be produced after exposure to a novel antigen Due to its pentameric structure, it has multiple antigen binding sites which results in overall high molecular valency- IgM plays an important role in the process of agglutination There are no subclasses of IgM

IgE
Heavy chain: EPSILON Its mean concentration in serum is less than 0.0005 mg/mL (NB IgE is the least abundant Ig in human serum) with half life of 2 days (NB IgE can have much longer half-life if surface-bound) Despite its low concentrations in serum, IgE has a very high potency. It binds Fc receptors on MAST CELL and BASOPHILS, and thereby triggers ALLERGIC reactions - by activation of mast cells and subsequent release of HISTAMINE and other inflammatory mediators (TNF-Alpha; prostaglandins; leukotriens; platelet activating factor; and cytokines IL-4 and IL-13 to perpetuate TH2 response) IgE has no recognised subclasses

IgD
Heavy chain: DELTA Its mean concentration in serum is less than 0.03 mg/mL with a half-life of 2 days Monomeric structure only IgD does not activate complement or cross the placenta It is highly unstable in serum and chiefly found on the surface of B cells rather than on its own Thus, its main function is to act as a RECEPTOR for CELL ACTIVATION IgD has no subclasses

SUMMARY

Function
Antigen binding Effector function

Parts of Immunoglobulin
Disulfide bonds Hinge region

Fxn related to structure


Fc

Variation
Isotype dependent independent

4 polypeptide chain Fab

location IgM IgE Blood and lymph fluid Mucuous membrane, skin, Lungs Tissue that line the belly and chest

Numbers 5-10% little

Fuction AB AB

Comment 1st to react largest Allergic reactions Parasitic reaction Maybe on B cell surface Little is known

IgD

Least abundant AB

Discussions
first immunoglobulin (Ig) to react to an infection is IgM if your IgM is high, then it is an acute infection. Then next to react is IgG, if it is high, then it is a chronic infection, 2 weeks or more. If both IgM and IgG arre in the normal range, then the infection must have been neutralized. IgE if its a parasitic infestation.

IgE if its a parasitic infestation. Little is known of IgD