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SN5 SHORT NOTE 5M

Describe the structure, classes and functions of the immunoglobulins.

Biochemistry · 1st Professional — Pre-Clinical

Definition

Immunoglobulins (antibodies) = glycoproteins produced by plasma cells that recognise and bind specific antigens.

Basic Structure

  • Y-shaped; four polypeptide chains — two identical heavy and two identical light chains
  • Held by interchain disulphide bonds
  • Light chains — two types, kappa (κ) and lambda (λ); a given molecule has one or the other, never both
  • Heavy chains determine the class — γ, α, μ, δ, ε for IgG, IgA, IgM, IgD, IgE
  • Variable region — antigen binding; constant region — effector functions
  • Hinge region gives flexibility; rich in proline

Enzymatic fragments

EnzymeFragments producedProperties
Papain2 Fab + 1 FcEach Fab is monovalent — binds but cannot precipitate
Pepsin1 F(ab′)2 + fragmentsBivalent — still precipitates antigen; Fc destroyed

Classes and Their Properties

ClassStructureProportionChief features
IgGMonomer75–80%The only one crossing the placenta; fixes complement; secondary response; longest half-life (23 days)
IgAMonomer in serum; dimer with secretory piece in secretions10–15%Chief antibody of mucosal secretions — milk, saliva, tears, gut
IgMPentamer5–10%Largest; first in the primary response; best complement fixer; natural blood group antibodies
IgDMonomer< 1%B cell surface receptor
IgEMonomerLeast (0.004%)Allergy and parasitic infection; binds mast cells and basophils

CLINICAL PEARL

Mnemonics — IgG Goes across the placenta; IgA in secretions (sAliva); IgM is Massive and first; IgE for Exposure and allergy.

Functions

  • Neutralisation of toxins and viruses
  • Opsonisation — coating organisms for phagocytosis
  • Complement activation — classical pathway; IgM > IgG
  • Agglutination and precipitation
  • Antibody-dependent cell-mediated cytotoxicity
  • Passive immunity to the newborn — IgG across the placenta, IgA in breast milk

Applied Aspects

  • Multiple myeloma — a monoclonal plasma cell tumour producing a sharp M band on electrophoresis; free light chains appear in urine as Bence Jones protein
  • Raised IgM alone in the newborn indicates intrauterine infection, since IgM cannot cross the placenta and must be the infant's own
  • Rh incompatibility — maternal IgG crosses the placenta and causes haemolytic disease; prevented by anti-D immunoglobulin
  • Monoclonal antibodies are now major drugs — rituximab, trastuzumab, infliximab, adalimumab
  • Selective IgA deficiency is the commonest primary immunodeficiency; recurrent mucosal infection and a risk of anaphylaxis on transfusion

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