CorpusHuman Anatomy
Lymphatic & ImmuneMolecule

Antibody (immunoglobulin)

Immunoglobulinum

Also known as: immunoglobulin, Ig, IgG, IgA, IgM, IgE, IgD, gamma globulin, antibodies

Y-shaped glycoproteins made by B cells and plasma cells, built from two heavy and two light chains, whose Fab arms bind antigen and whose Fc stem recruits effector functions; there are five classes — IgG, IgA, IgM, IgE and IgD.

Adaptive Immune Response

Overview

Serum abundanceIgG ≈ 75–80% > IgA ≈ 10–15% > IgM ≈ 5–10% > IgD < 1% > IgE trace
Half-lifeIgG ≈ 21–23 days; IgA ≈ 6 days; IgM ≈ 5 days; IgE ≈ 2 days
κ : λ light chains≈ 2 : 1
Antigen-binding sitesIgG 2; secretory IgA 4; IgM pentamer 10

The basic antibody unit (≈ 150 kDa for IgG) consists of two identical heavy chains and two identical light chains (either κ or λ; κ:λ ≈ 2:1 in humans) held together by disulfide bonds. Each chain is built of ≈ 110-amino-acid immunoglobulin domains: the N-terminal variable (V) domains of one heavy and one light chain together form an antigen-binding site, whose specificity is determined by three hypervariable complementarity-determining regions (CDRs) on each chain (CDR3 being the most variable). The remaining constant (C) domains of the heavy chain define the class (isotype) — γ, α, μ, ε or δ.

Proteolysis reveals the functional division: papain cuts at the flexible hinge to release two Fab fragments (fragment antigen-binding, each with one binding site) and one Fc fragment (fragment crystallisable); pepsin yields a single bivalent F(ab′)₂. The Fab arms give specificity; the Fc region determines what the antibody does next — binding Fc receptors on phagocytes, NK cells and mast cells, activating complement via C1q, and binding the neonatal Fc receptor (FcRn), which transports IgG across the placenta and protects it from degradation (hence its long half-life).

Antibodies protect by neutralisation (blocking toxins and microbial attachment), opsonisation (coating microbes for phagocytosis), complement activation, antibody-dependent cell-mediated cytotoxicity (NK cells via CD16), agglutination and mucosal immune exclusion, and IgE sensitises mast cells. Clinical laboratories exploit their specificity in countless assays, and engineered monoclonal antibodies (named "-mab": -ximab chimeric, -zumab humanised, -umab fully human) are now major drugs.

Location

Plasma and interstitial fluid (IgG, IgM, monomeric IgA), mucosal secretions and breast milk (secretory IgA), surfaces of B cells (IgM, IgD) and mast cells/basophils (IgE).

Parts & subdivisions

  1. IgG
    Monomer; ≈ 75–80% of serum Ig (≈ 7–16 g/L); four subclasses (IgG1 > IgG2 > IgG3 > IgG4). Main antibody of the secondary response; the only class that crosses the placenta (FcRn); best opsonin; activates complement (IgG3 > IgG1); mediates ADCC; neutralises toxins and viruses. Longest half-life ≈ 21–23 days.
  2. IgA
    Monomer in serum (≈ 10–15%; ≈ 0.7–4 g/L); dimer with J chain and secretory component in tears, saliva, mucus, bile, colostrum and breast milk. Most abundant antibody produced overall (mucosal). Neutralises at mucosal surfaces without inflammation; does not activate the classical complement pathway.
  3. IgM
    Pentamer (J chain) in serum (≈ 5–10%; ≈ 0.4–2.3 g/L); monomer as the naive B-cell receptor. First antibody made in a primary response and by the fetus; 10 binding sites give high avidity — excellent at agglutination and the most efficient activator of classical complement. Natural IgM includes the ABO isohaemagglutinins. Does not cross the placenta.
  4. IgE
    Monomer with an extra constant domain; trace serum levels (< 0.01% of immunoglobulin). Binds FcεRI on mast cells and basophils with very high affinity; triggers type I hypersensitivity and defends against helminths (with eosinophils). Serum half-life ≈ 2 days but persists for weeks bound to mast cells.
  5. IgD
    Monomer; < 1% of serum Ig. Co-expressed with IgM on the surface of mature naive B cells as part of the B-cell receptor; secreted function uncertain (may arm basophils in the upper airway).
  6. Fab and Fc regions
    Fab: antigen binding (variable domains, CDRs). Fc: effector functions (Fc receptors, C1q, FcRn); determines isotype.
  7. Heavy and light chains
    Heavy chain class γ, α, μ, ε or δ; light chain κ or λ. Each B cell expresses only one heavy-chain allele and one light-chain type (allelic and isotypic exclusion).

Function

  • Neutralisation of toxins, viruses and bacterial adhesins.
  • Opsonisation for phagocytosis by neutrophils and macrophages.
  • Activation of the classical complement pathway.
  • Antibody-dependent cell-mediated cytotoxicity (NK cells, eosinophils).
  • Agglutination and precipitation of antigen.
  • Mucosal protection (secretory IgA) and passive immunity of the fetus and newborn (IgG, breast-milk IgA).
  • Sensitisation of mast cells and basophils (IgE).
Physiology

Serum concentrations (adult): IgG ≈ 7–16 g/L, IgA ≈ 0.7–4 g/L, IgM ≈ 0.4–2.3 g/L. Newborns have adult IgG levels from the mother but little IgM or IgA; maternal IgG falls to a nadir at ≈ 3–6 months (physiological hypogammaglobulinaemia) before the infant's own production rises. On serum protein electrophoresis immunoglobulins form the broad γ region; a narrow spike (paraprotein) indicates a monoclonal population.

Clinical significance

Haemolytic disease of the fetus and newborn

An RhD-negative mother sensitised by RhD-positive fetal red cells (usually at a previous delivery) makes anti-D IgG, which crosses the placenta in later pregnancies and destroys fetal red cells (anaemia, hydrops, kernicterus). Prevented by giving anti-D immunoglobulin to RhD-negative mothers antenatally and after sensitising events. ABO incompatibility is usually mild because anti-A/anti-B are mostly IgM.

Immunoglobulin replacement and passive antibody

Intravenous or subcutaneous immunoglobulin (pooled IgG) treats antibody deficiencies (XLA, CVID) and, at high dose, autoimmune conditions (ITP, Guillain–Barré, Kawasaki disease). Specific immunoglobulins (tetanus, rabies, hepatitis B, varicella-zoster, antivenom) give immediate but temporary protection.

Selective IgA deficiency

The commonest primary immunodeficiency; most are asymptomatic, some have recurrent sinopulmonary or giardial infections, coeliac disease or autoimmunity. Anti-IgA antibodies can cause anaphylaxis to blood products, and IgA-based serological tests (e.g. anti-tTG IgA) may be falsely negative.

Mnemonics

"GAMED"

G — crosses the placenta, dominates secondary responses; A — mucosal dimer (tears, saliva, milk); M — Mammoth pentamer, Made first; E — allErgy and worms (mast cells); D — on naive B cells with IgM.

Test yourself

Which immunoglobulin crosses the placenta?
  1. IgA
  2. IgM
  3. IgG
  4. IgE

Answer: IgG

Only IgG is actively transported across the syncytiotrophoblast by the neonatal Fc receptor (FcRn), giving the newborn passive immunity for ≈ 6 months. IgM is too large, which is why fetal IgM indicates congenital infection.

More lymphatic & immune system questions

Compiled from standard anatomy and physiology references — see the Lymphatic & Immune System sources. For education only; not medical advice.