Antigen Recognition and Antibodies

Antigen Recognition: Immunoglobulins (Antibodies)

• Antibodies are immunoglobulin molecules with specificity for an epitope of antigen molecules, synthesized by B lymphocytes (B cells) and secreted by plasma cells.
• Antibodies provide protection by neutralizing viruses or toxins, enhancing phagocytosis and leukocyte degranulation, and activating complement activation with subsequent lysis.

Structure of Immunoglobulins

• Human immunoglobulin contains four polypeptides: two identical light chains and two identical heavy chains linked by disulfide bonds.
• Antibody molecules share the same basic structural characteristics but display remarkable variability in the regions that bind antigens.
• Heavy chains and light chains consist of amino-terminal variable (V) regions that participate in antigen recognition and carboxy-terminal constant (C) regions that mediate effector functions.

Hypervariable Regions and Antigen Binding

• Hypervariable regions of VH and VL are responsible for antigen binding by antibody molecules.
• Three short stretches in the V region of the heavy chain and three stretches in the V region of the light chain exhibit the greatest diversity, known as hypervariable regions.

Classes of Immunoglobulins

• Antibody molecules can be divided into distinct classes and subclasses based on differences in the structure of their heavy chain C regions.
• Classes of antibody molecules, also called isotypes, are named IgA, IgD, IgE, IgG, and IgM, each performing different effector functions.

Antibody Class Switching and B Cell Activation

• B cells initially express only IgD and IgM antibodies, and the class is determined by the constant region (Fc) of the heavy chain.
• B cells can switch to one of the other classes of antibody (IgA, IgE, or IgG) by replacing the tail region of the antibody in response to chemical messengers (cytokines) from T helper cells.

Bifunctional Antibodies

• Antibodies recognize and bind antigen, and promote the killing and/or removal of the immune complex through activation of effector mechanisms.

Immunoglobulin Variability

• There are three types of immunoglobulin variability: isotypic variation (present in the germline of all members of a species), allotypic variation (intraspecies allelic variability), and idiotypic variation (diversity at the antigen-binding site).

Primary vs. Secondary Immune Response

• Primary response: Lag phase (5-10 days), peak concentration (relatively low), Ig class (IgM – early response then IgG), average antibody affinity (relatively low), and responding cell (resting B cell).
• Secondary response: Lag phase (2-5 days), peak concentration (relatively high), Ig class (IgG predominates), average antibody affinity (relatively high), and responding cell (memory B cell).