Introduction to Immunoglobulin Isotypes to Thymus-Dependent Antigens

Content August 26, 2025

Immunoglobulin isotypes

All isotypes can exist as monomers. Mature, naive B cells prior to activation express IgM and IgD on their surfaces. They may differentiate in germinal centers of lymph nodes by isotype switching (gene rearrangement, induced by cytokines and CD40L) into plasma cells that secrete IgA, IgG, or IgE. For B cells, IgM and IgD mature to plasma cells as they AGE. Affinity refers to the individual antibody-antigen interaction, while avidity describes the cumulative binding strength of all antibody-antigen interactions in a multivalent molecule.

IgG

#boundingbox

Main antibody in 2° response to an antigen. Most abundant isotype in serum. Fixes complement, opsonizes bacteria, neutralizes bacterial toxins and viruses. Only isotype that crosses the placenta (provides infants with passive immunity that starts to wane after birth). “IgG Greets the Growing fetus.” Associated with warm autoimmune hemolytic anemia (“warm weather is Great”).

IgA

#boundingbox

Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement. Monomer (in circulation) or dimer (with J chain when secreted). Crosses epithelial cells by transcytosis. Produced in GI tract (eg, by Peyer patches) and protects against gut infections (eg, Giardia). Most produced antibody overall, but has lower serum concentrations. Released into secretions (tears, saliva, mucus) and breast milk. Picks up secretory component from epithelial cells, which protects the Fc portion from luminal proteases.

IgM

#boundingbox

Produced in the 1° (IMmediate) response to an antigen. Fixes complement. Antigen receptor on the surface of B cells. Monomer on B cell, pentamer with J chain when secreted. Pentamer enables avid binding to antigen while humoral response evolves. Associated with cold autoimmune hemolytic anemia.

IgD

#boundingbox

Unclear function. Found on surface of many B cells and in serum.

IgE

#boundingbox

Binds mast cells and basophils; cross-links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine. Contributes to immunity to parasites by activating Eosinophils.

Antigen type and memory

Thymus-independent antigens

Antigens lacking a peptide component (eg, lipopolysaccharides from gram ⊝ bacteria), cannot be presented by MHC to T cells. Weakly immunogenic, vaccines often require boosters and adjuvants (eg, capsular polysaccharide subunit of Streptococcus pneumoniae PPSV23 vaccine).

Thymus-dependent antigens

Antigens containing a protein component (eg, diphtheria toxoid). Class switching and immunologic memory occur as a result of direct contact of B cells with Th cells.

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