LECTURE #5 ANTIBODY STRUCTURE AND FUNCTION

After studying lecture #5, you should be familiar with the following concepts.
1. Lymphocyte clones. Each nave B and T cell expresses its own unique BCR or TCR.
Each BCR and TCR has a unique antigen specificity. Activated B or T cells expand
clonally, that is they produce a population of lymphocytes that are identical to the
parental lymphocytes. This means that a novel antigen drives the expansion of a clonal
population of lymphocytes with receptors specific for the antigen.
2. B cells and B cell activation. B cells arise from bone marrow stem cells. During
development in the bone marrow, B cells commence expression of their BCR. Cells that
successfully express a BCR exit the bone marrow and enter circulation where they
search for antigens. B cell antigens are three-dimensional extracellular molecules.
Detection of antigen in combination with a second signal causes the secretion of a
soluble form of the BCR the antibody.
3. Antibody structure. The core antibody structure consists of two identical light chains
and two identical heavy chains that are held together through a series of disulfide
bridges. Light chains contain a variable domain and a constant domain. Heavy chains
contain a variable domain and at least three constant domains. The combined variable
regions (from the light and heavy chain) bind antigen. The constant regions are
conserved and mediate effector functions.
4. Antibody Isotypes. There are several distinct types (Isotypes) of antibody. IgA: Two
IgA molecules are joined by a J chain. The J chain facilitates transport across epithelia
and contributes to mucosal immunity and neonatal passive immunity. IgD: Unknown
function. IgE: Upon first encounter with antigen, IgE is secreted as a monomer and binds
the Fc receptor of mast cells. The next encounter with antigen causes IgE cross-linking
and mast cell degranulation. This is a major feature of allergic responses. IgE is
speculated to be important for anti-parasitic defenses. IgG: The major serum Ig Isotype.
IgG governs numerous features of the immune responses, such as the binding and
neutralization of toxins; opsonization of pathogens; activation of phagocytosis; and
induction of antibody-dependent cellular cytotoxicity. IgM: The first antibody expressed in
mature B cells. Exists as a pentamer (10 distinct antigen binding sites!) with a J chain
that facilitates IgM secretion.
5. Affinity and Avidity. Affinity refers to the strength with which a single antigen binding
site of an Ig Isotype binds antigen. Avidity refers to the combined affinities of the entire
isotype. This means that IgM (the first isotype produced during an infection) with 10
antigen binding sites often has a very high avidity for its antigen.
Prepared by E. Foley