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Immunology

Immunoglobulins: 5 classes of antibodies — structure and functions

WhiteCoat Pro Editorial BoardApril 11, 20263 min read
Table of contents · 7 sections
  1. General Structure of Immunoglobulins
  2. Five Classes of Immunoglobulins: Comparison Table
  3. IgG: The Main Defender
  4. Primary vs. Secondary Immune Response
  5. IgE and Allergy (Type I Hypersensitivity)
  6. Clinical Applications
  7. Frequently asked questions

Immunoglobulins (antibodies) are glycoproteins produced by plasma cells (mature B lymphocytes) in response to antigenic stimulation. The five antibody classes (IgG, IgA, IgM, IgD, IgE) differ in structure, function, and clinical significance. Knowledge of immunoglobulins is essential for understanding the immune response, allergies, autoimmune diseases, and serological diagnostics.

General Structure of Immunoglobulins

All antibodies consist of 4 polypeptide chains: 2 heavy (H) and 2 light (L) chains, connected by disulfide bonds:

  • Fab fragment (Fragment antigen-binding) — variable region, binds antigen. Each antibody has 2 binding sites
  • Fc fragment (Fragment crystallizable) — constant region, determines the Ig class and biological functions (complement activation, binding to Fc receptors, placental crossing)
  • Hinge region — provides molecular flexibility when binding epitopes

Heavy chains determine the class: γ (IgG), α (IgA), μ (IgM), δ (IgD), ε (IgE).

Five Classes of Immunoglobulins: Comparison Table

Class% in serumStructureMain functionsPrimary location
IgG75-80 %MonomerMain Ig of secondary response, opsonization, complement activation (classical pathway), toxin neutralizationBlood, tissues. The only one that crosses the placenta!
IgA10-15 %Dimer (secretory IgA)Protection of mucous membranes, surface neutralizationMucous membranes: GI tract, respiratory tract, colostrum, saliva, tears
IgM5-10 %PentamerPrimary immune response (first Ig in infection), strongest complement activator, isohemagglutinins (blood groups)Blood (large molecule — does not cross into tissues)
IgD<1 %MonomerReceptor on the surface of naive B lymphocytes (BCR)B-cell membrane
IgE<0,01 %MonomerAllergic reactions (Type I hypersensitivity), anti-parasitic defenseAssociated with mast cells and basophils via FcεRI

IgG: The Main Defender

  • 4 subclasses: IgG1 (65 %) > IgG2 (25 %) > IgG3 (7 %) > IgG4 (3 %)
  • The only Ig that crosses the placenta (via FcRn — neonatal Fc receptor) → passive immunity of the newborn in the first 3–6 months
  • Opsonization (via phagocyte Fc receptors) and ADCC (antibody-dependent cell-mediated cytotoxicity — NK cells)
  • Complement activation via the classical pathway (IgG1 and IgG3 are the best activators)

Primary vs. Secondary Immune Response

ParameterPrimary responseSecondary response
Lag phase7–10 days1–3 days
First IgIgMIgG (rapid class switching)
Antibody titerLowHigh (100–1000 times higher)
AffinityLowHigh (affinity maturation)
CellsNaive B → plasma cellsMemory B cells → plasma cells

This is why IgM (+) with IgG (−) = acute infection; IgM (−) with IgG (+) = past infection or vaccination.

IgE and Allergy (Type I Hypersensitivity)

  1. Sensitization: first contact with allergen → B cells → IgE → IgE binds to mast cells via FcεRI
  2. Re-exposure: allergen cross-links 2 IgE molecules on a mast cell → degranulation → histamine, leukotrienes, prostaglandins
  3. Clinical presentation: urticaria, rhinitis, bronchospasm, anaphylaxis

Elevated total IgE: atopic diseases (asthma, eczema, rhinitis), helminthiasis, allergic bronchopulmonary aspergillosis.

Clinical application

  • Serological diagnostics: detection of IgM and IgG against pathogens (TORCH infections, hepatitis, HIV)
  • Immunoelectrophoresis: diagnosis of multiple myeloma (monoclonal paraprotein — M-spike)
  • IgA deficiency: most common primary immunodeficiency (1:500), often asymptomatic; risk of anaphylaxis during blood transfusion containing IgA
  • Intravenous immunoglobulins (IVIG): therapy for autoimmune diseases (Guillain-Barré syndrome, Kawasaki disease, ITP)

Frequently asked questions

Why is IgM a pentamer while IgG is a monomer?

IgM is the primary response antibody, produced before affinity maturation. Its low affinity is compensated by 10 binding sites (pentamer) — high avidity. IgG appears after class switching and affinity maturation — each molecule is highly specific, so 2 binding sites are sufficient. The pentameric structure also makes IgM the most potent complement activator.

How does IgG cross the placenta?

Via FcRn (neonatal Fc receptor) on the syncytiotrophoblast: IgG binds at pH 6.0 (in endosomes), is transported across the cell, and is released at pH 7.4 (in fetal blood). This mechanism is selective — IgM, IgA, and IgE do not pass due to incompatibility with FcRn. Transplacental IgG protects the newborn for the first 3–6 months.

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