Heavy Chains – Isotypic Differences

Idiotypic Differences

• The idiotype is the antigenic characteristic of the variable region of an Ab

• Note that the same isotype of Ab (IgG) can have idiotypic differences

IgG• The major Ig isotype in serum • Most important class in

secondary immune responses.• Involved in activation of the

classical pathway of complement.

• Functions as an opsonin.• Crosses placenta (neonatal

immunity).• Important in antigen-

dependent cell mediated cytotoxicity (ADCC)

• Possesses neutralizing properties

Adapted from Roitt’s Immunology 3-12 & Similar to Abbas & Lichtman’s Basic Immunology 4-3

3 conserved domains

in heavy chain

What is Antibody Neutralization?

Normal receptor:ligandinteraction

Antibody blocks receptor:ligand interaction

Antibodies are relatively large molecules. Binding to the epitope of an antigen may mean functional inactivation or “neutralization” of the antigen.

IgM

• Pentameric.• Most prominent class in

the primary immune response.– Naïve B cell antigen

receptor.

• Potent activator of the classical pathway of the complement cascade.

• Excellent at neutralizing toxins and viruses

• Does not cross the normal placenta

Adapted from Roitt’s Immunology 4-6 & Similar to Abbas & Lichtman’s Basic Immunology 4-3

4 conserved domains

in heavy chain.

IgA

• Soluble form is assembled as a dimer.

• Passes through epithelial membranes.

• Present in nasal secretions, saliva, _tears, GI tract, and milk.– Neonatal passive immunity.

• Important in mucosal immunity.

Adapted from Roitt’s Immunology 4-6 & Similar to Abbas & Lichtman’s Basic Immunology 4-3

Transistion of IgA across Mucosal Epithelium:

IgA

Poly Ig receptor

Secreted IgA with Secretory Component

PlasmaCell

Epithelial CellsPlasmaCell

ECFLamina Propria

IgD

• Naïve B cell receptor.

• May play a role in antigen triggered lymphocyte differentiation.

Adapted from Roitt’s Immunology 4-6 & Similar to Abbas & Lichtman’s Basic Immunology 4-3

IgE

• Binds strongly to basophils and mast cells. (via Fc receptors).

• Plays a role in immunity from parasites.

• Associated with Type I hypersensitivity reactions (allergic responses ie. asthma and hay fever).

Adapted from Roitt’s Immunology 4-6 & Similar to Abbas & Lichtman’s Basic Immunology 4-3

IsotypeThe Most Important Features of Ig Isotypes

Feature IgG IgA IgM IgD IgE

Concentration +++ ++ + +/- -In Serum

Serum half-life (days) 23 5.5 5.0 2.8 2.0

Placental ++ - - - -Passage

Presence in - ++ - - -Secretions

Activation of + - +++ - - Complement

Opsonization ++ - ++ - -Activity

Neutralizing +++ ++ +++ - -Activity

Allergic Activity - - - - ++

Antibody Diversity• Antibody diversity provides enough different binding sites

to recognize the millions of antigenic shapes.• Isotypic variation.

– Different classes of light ( and and heavy chain (, , , , .

• _Allotypic variation_.– Different alleles for the light and heavy chain genes.

• Idiotypic variation.– Variations in the variable domains of light and heavy chains.

Next Time

• Compare and contrast the 5 Ig classes with respect to:– General structure

– Function

– Biological activity

– Concentrations in normal serum and bodily secretions

• T cell receptors- What are they and where do they fit into immunology?

• Readings: Abbas & Lichtman, Chapters 4 & 7

Objectives

1. Describe antibodies in general.1. Structure, function, isotypes, diversity

2. Know the difference between isotype and idiotype.

3. Describe the structure and functions of the various antibody isotypes.

1. IgG, IgM, IgA, IgD, IgE