U01.02.017 Immunoglobulin isotypes

Immunoglobulins (antibodies) are glycoproteins produced by B cells. They play a central role in adaptive immunity by recognizing and neutralizing antigens. Isotype differentiation occurs through isotype switching (gene rearrangement), cytokine- and CD40L-dependent. Mature, naïve B cells express IgM and IgD, and upon activation, may secrete IgA, IgE, or IgG as plasma cells.

Key Definitions

Affinity: Strength of interaction between an individual antigen and an antibody.
Avidity: Combined binding strength of multiple interactions in multivalent antibodies.

Immunoglobulin Isotypes: Features and Functions

Summary Table

Isotype	Main Function	Structure	Special Features
IgG	Main antibody in secondary immune response	Monomer	Crosses placenta (passive immunity), fixes complement, neutralizes toxins and viruses, opsonization.
IgA	Prevents microbial attachment to mucosal surfaces	Monomer (circulation), Dimer (secretions with J chain)	Found in secretions (tears, saliva, breast milk), protects against GI infections, transcytosis across epithelium.
IgM	Primary immune response antibody	Monomer (B cell), Pentamer (secreted with J chain)	Fixes complement, high avidity for antigens. First antibody produced in response to infection.
IgD	Unclear function	Monomer	Found on B cell surfaces and in serum.
IgE	Mediates type I hypersensitivity and immunity against parasites	Monomer	Binds mast cells and basophils, cross-links during allergen exposure, activates eosinophils.

Detailed Features

IgG

Function:
- Major antibody in secondary immune response.
- Most abundant antibody in serum.
- Neutralizes bacterial toxins and viruses.
- Fixes complement and facilitates opsonization.
Special Feature: Crosses placenta, providing passive immunity to the fetus (“IgG Greets the Growing fetus”).

IgA

Function:
- Prevents microbial attachment to mucous membranes.
- Does not fix complement.
Structure:
- Monomer in circulation.
- Dimer in secretions (tears, saliva, mucus, and breast milk) with J chain.
Special Feature:
- Picks up a secretory component from epithelial cells, protecting it from degradation by luminal proteases.

IgM

Function:
- The first antibody is produced during a primary immune response.
- Fixes complement.
- Serves as a B-cell antigen receptor.
Structure:
- Monomer on B cells.
- Pentamer with J chain when secreted, allowing high avidity binding.

IgD

Function: Unclear but found on the surface of B cells and in serum.

IgE

Function:
- Mediates immediate (type I) hypersensitivity through mast cell and basophil activation.
- Contributes to defense against parasites by activating eosinophils.

Points to Remember

Affinity vs. Avidity: Affinity relates to individual antibody-antigen interactions, while avidity is the cumulative binding strength in multivalent interactions.
Isotype Switching: Driven by cytokines and CD40L in germinal centers of lymph nodes.
IgG: Provides passive immunity to the fetus and is most abundant in the serum.
IgA: Predominantly found in mucosal secretions, vital for mucosal immunity.
IgM: First antibody produced; pentameric structure enables strong antigen binding.
IgE: Key in allergic reactions and parasitic defense.

References

Abbas, A. K., Lichtman, A. H., & Pillai, S. Cellular and Molecular Immunology.
Janeway, C. A., et al. Immunobiology.
Kumar, V., et al. Robbins and Cotran Pathologic Basis of Disease.

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