STEPTRACKERIMMUNOLOGY | ADAPTIVE IMMUNITY | HIGH-YIELD REVIEW

Antibody Structure & Isotypes

Two heavy and two light chains: the Fab arms bind antigen, the Fc tail decides what happens next. Each isotype is built for one place and one job.

FOCUS ON

Structure: 2 heavy + 2 light (κ or λ) chains, disulfide-linked; Fab (variable regions, hypervariable CDRs → antigen binding; idiotype) and Fc (constant heavy chain → complement binding, Fc receptors; isotype). Papain → 2 Fab + Fc. IgG: most abundant, secondary response, crosses placenta, opsonizes, fixes complement, neutralizes, ADCC. IgA: mucosal (dimer with J chain + secretory component), breast milk; monomer in blood. IgM: first made, pentamer, best complement activator, surface BCR, doesn't cross placenta. IgE: binds mast cells/basophils (FcεRI), allergy, helminths; lowest level. IgD: naive B-cell surface. Monoclonal spike → myeloma (IgG > IgA), Waldenström (IgM).

ISOTYPE

FORM · LOCATION

FUNCTION

CLINICAL LINK

IgG

Monomer; ~75% of serum Ig; subclasses 1–4

Opsonization (FcγR), complement (IgG1, IgG3), neutralization, ADCC, secondary response

Only isotype crossing placenta (FcRn) → newborn protection, Rh disease, neonatal Graves/myasthenia

IgA

Dimer + J chain + secretory component in secretions; monomer in serum

Neutralizes at mucosa; doesn't fix complement well

Selective IgA deficiency (most common) · IgA nephropathy, HSP · IgA proteases of S pneumoniae, Hib, Neisseria

IgM

Pentamer + J chain in serum; monomer on naive B cells

First response, strongest complement activation, agglutination

Cold agglutinins (Mycoplasma, EBV), ABO isohemagglutinins, Waldenström

IgE

Monomer; lowest serum level; bound to FcεRI on mast cells, basophils

Type I hypersensitivity, helminth defense with eosinophils

↑ in atopy, ABPA, hyper-IgE syndrome · omalizumab

IgD

Naive B-cell surface with IgM

Unclear; B-cell activation

—

Fab region

Variable heavy + light chains; CDRs form the binding site

Antigen specificity (idiotype)

Digoxin immune Fab, CroFab antivenom

Fc region

Constant heavy chains (CH2/CH3)

Binds C1q and Fc receptors; determines isotype; carbohydrate side chains

FcRn recycles IgG (long half-life ~3 weeks)

Light chains

κ or λ (one type per B cell)

—

Clonality: κ:λ ratio · Bence Jones proteins (free light chains) in myeloma → cast nephropathy, AL amyloid

Allotype · idiotype

Inherited constant-region variants · unique variable-region shape

—

Anti-idiotype antibodies

Antibody functions

Neutralization, opsonization, complement activation, ADCC (NK cells via CD16)

—

Monoclonal antibody drugs use these

Newborn immunity

Maternal IgG (placenta) + IgA (breast milk); own IgM at birth

Physiologic nadir 3–6 months

IgM in cord blood → congenital infection

Picture it — antibody shapes

The antibody unitTwo heavy and two light chains joined by disulfide bonds; the tips of the Fab arms bind antigen and the Fc stem talks to complement and Fc receptors.

Polymeric isotypesIgG circulates as a monomer; secretory IgA is a dimer with J chain and secretory component; serum IgM is a pentamer that activates complement best.

Schematic diagrams, not to scale.

Mechanism — how antibodies protect

NeutralizationBlock toxin or viral binding (IgG, IgA)

OpsonizationFc → phagocyte FcγR (IgG)

ComplementC1q on IgM, IgG1/3

ADCCNK CD16 binds IgG; eosinophils use IgE

Isotypes at a glance

ISOTYPE

FORM

PLACENTA

COMPLEMENT

IgG

Monomer

Yes

Yes (IgG1, 3)

IgA

Dimer (secretory)

Weak (lectin/alt)

IgM

Pentamer

Strongest

IgE

Monomer

IgD

Monomer

How it's tested

COMMON CONFUSIONIgM in a newborn's blood means the baby made it (congenital infection); IgG may simply be the mother's.

THE TRAPSelective IgA deficiency can cause anaphylaxis to transfusions (anti-IgA antibodies) — give washed or IgA-deficient blood.

YOUR APPROACHLocation and timing (mucosa, blood, placenta, first vs repeat exposure) → isotype → function → disease when it fails or is overproduced.

If you see… think…

Antibody that crosses the placenta → IgG

Antibody in breast milk and tears → secretory IgA

Largest antibody, first made, best at complement → IgM pentamer

Antibody bound to mast cells → IgE

Antigen-binding fragment → Fab

Region binding C1q and Fc receptors → Fc

Anaphylaxis during transfusion in a patient with few infections → IgA deficiency

Free light chains in urine → Bence Jones proteins (myeloma)

IgM monoclonal spike with hyperviscosity → Waldenström macroglobulinemia

Receptor that prolongs IgG half-life → FcRn