1. Heavy Chains – Isotypic Differences
Lecture #8
Heavy Chains – Isotypic Differences
Really just more terminology for you to learn – isotype and idiotype.

2. Idiotypic Differences
Lecture #8
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

3. 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
3 conserved domains
in heavy chain
Adapted from Roitt’s Immunology 3-12 & Similar to Abbas & Lichtman’s Basic Immunology 4-3

4. What is Antibody Neutralization?
Lecture #8
What is Antibody Neutralization?
Antibody blocks receptor:
ligand interaction
Normal receptor:ligand
interaction
I didn’t explain this in the notes b/c it is somewhat self explanatory – a “neutralizing” Ab simply neutralizes the properties of whatever it binds to
Antibodies are relatively large molecules. Binding to the epitope of an antigen may mean functional inactivation or “neutralization” of the antigen.

5. 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
4 conserved domains
in heavy chain.
Adapted from Roitt’s Immunology 4-6 & Similar to Abbas & Lichtman’s Basic Immunology 4-3

6. 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

7. Transistion of IgA across Mucosal Epithelium:
Lecture #8
Transistion of IgA across Mucosal Epithelium:
Lamina Propria
ECF
Epithelial Cells
Plasma
Cell
Secreted IgA with
Secretory Component
IgA
Plasma
Cell
IgA secreting plasma cells are located predominantly in the lamina propria, which is the layer of connective tissue underlying the epithelium of a mucous membrane (ie. parotid gland, in intestinal villi of the GI tract, tear glands, lactating breast, beneath bronchial mucosa)
Dimeric IgA is released from plasma cells and binds the poly Ig receptor expressed on the basal membranes of epithelial cells
The receptor transports the IgA through the cell and releases them into extracellular fluids which is facilitated by enzymatic cleavage of the Poly Ig receptor – the Ab leaves the Epithelial cells with the secretory component it obtained from epithelial cells
Poly Ig
receptor

8. 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

9. 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

10. The Most Important Features of Ig Isotypes
Feature IgG IgA IgM IgD IgE
Concentration /- -
In Serum
Serum half-life (days)
Placental
Passage
Presence in
Secretions
Activation of
Complement
Opsonization
Activity
Neutralizing
Allergic Activity

11. Antibody Diversity
Antibody diversity provides enough different binding sites to recognize the millions of antigenic shapes.
Isotypic variation.
Different classes of light (k and l) and heavy chain (g1-4, a1-2, m, e, d).
_Allotypic variation_.
Different alleles for the light and heavy chain genes.
Idiotypic variation.
Variations in the variable domains of light and heavy chains.

12. 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

13. Objectives Describe antibodies in general.
Structure, function, isotypes, diversity
Know the difference between isotype and idiotype.
Describe the structure and functions of the various antibody isotypes.
IgG, IgM, IgA, IgD, IgE