What are the five major classes of antibodies. What specific role does each play in humoral immunity?
The mnemonic is GAMED:
• G—IgG: highest concentration in serum (70% of total Igs) and excellent penetration into tissues. Can cross the placenta by week 16 of pregnancy. Fixes complement. Four subtypes: IgG1 and IgG3 respond to protein antigens; polysaccharide antigens elicit IgG2 responses; IgG4 arises against nematodes and can dampen chronic inflammation.
• A—IgA: despite its low concentration in serum, more IgA is produced than any other Ig isotypes. Most IgA exists as secretory IgA in mucosal cavities and milk. There are two subclasses: IgA1 is a monomer in serum and IgA2 is a dimer/polymer and is the most important antibody for host defense at mucosal surfaces (sites of antigen entry). Dimer/polymeric IgA2 contains a J-chain. This complex is produced locally by plasma cells, captured by a receptor on the basolateral surface of epithelial cells, transported to the apical side, and cleaved from the receptor. IgA is released into secretions associated with a secretory component. This form (secretory IgA) is more resistant to enzymatic degradation.
• M—IgM: IgM is the first class of antibody made in the primary response to antigen. Pentameric form vigorously fixes complement and is very important in host defense against blood-borne antigens. IgM also associates with a J-chain, which allows its active transport to mucosal surfaces. A monomeric form of IgM complexed with Igα and Igβ on the surface of naïve B cells and serves as the BCR.
• E—IgE: binds to the surface of mast cells and basophils by high-affinity IgE Fc receptor, FcεR1. Crosslinking of IgE by antigen binding results in the release of the cells granular contents (primarily histamine). Important in allergic diseases and host defense against parasites.
• D—IgD: found primarily as a membrane Ig on the surface of naïve B cells. B cells with IgD on their surface are more resistant to being tolerized.