Learning Objective:
Describe the structure and functions of antibody isotypes (IgA, IgD, IgE, IgG, IgM), their distribution, and their clinical relevance for USMLE Step 1.
General Principles
- All isotypes (IgM, IgD, IgG, IgA, IgE) can exist as monomers.
- Naïve mature B cells express IgM and IgD on their surface before activation.
- During an immune response, B cells undergo isotype (class) switching in the germinal center—guided by CD40–CD40L interaction and cytokines—to produce IgA, IgG, or IgE.
- IgM, IgD → naïve B cells
- IgA, IgG, IgE → post-class-switch plasma cells
Affinity: Strength of a single antigen–antibody interaction
Avidity: Combined strength of all interactions in a multivalent molecule (e.g., IgM pentamer)
Activity:
Functions of Each Immunoglobulin Isotype
IgG
- The main antibody in the secondary response
- Most abundant in serum
- Fixes complement
- Opsonizes bacteria
- Neutralizes bacterial toxins and viruses
- Only antibody that crosses the placenta → passive neonatal immunity
- Associated with warm autoimmune hemolytic anemia (“warm is Good”)
Activity:
IgA
- Prevents adherence of bacteria and viruses to the mucosa
- Does NOT fix complement
- Monomer in circulation; dimer with J chain in secretions
- Transported across the epithelium via transcytosis
- Most produced immunoglobulin overall (but with low serum levels)
- Found in:
- GI tract (Peyer patches)
- Tears, saliva, mucus
- Breast milk
- Picks up the secretory component for protection against proteases
Activity:
IgM
- The first antibody produced in any immune response
- Fixes complement
- Monomer on B cells (BCR)
- Pentamer when secreted (with J chain) → high avidity
- Marker of recent infection
- Associated with cold autoimmune hemolytic anemia
IgD
- Co-expressed with IgM on naïve mature B cells
- Very low serum concentration
- Function not fully defined
Activity:
IgE
- Binds mast cells and basophils
- Cross-links on allergen exposure → Type I hypersensitivity (histamine release)
- Activates eosinophils → immunity against parasites (helminths)
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