An Immunoglobulin’s Constant Region Determines Its Functional Properties

As we have seen, antibodies recognize antigen via their variable regions. Their constant regions determine which effector molecules they recruit to neutralize the pathogen.

Antibodies attached to a viral or microbial surface can be recognized directly by cells that express receptors specific for the Fc portion of immunoglobulins. These Fc receptors (FcRs), which are specific for individual classes and subclasses of immunoglobulins, display considerable structural and functional heterogeneity. By means of FcR-dependent events, specialized phagocytic cells such as dendritic cells and macrophages can engage antibody-decorated particles, then ingest and destroy them. The noncovalent decoration of an antigenic target with antibodies, or its covalent modification with complement components, is called opsonization. FcR-dependent events also allow some immune-system cells (e.g., monocytes and natural killer cells) to directly engage target cells that display viral or other antigens to which antibodies are attached. This engagement may induce the immune-system cells to release toxic small molecules (e.g., reactive oxygen species) or the contents of cytotoxic granules, including perforins and granzymes. Perforins are proteins that can attach themselves to the surface of the engaged target cell and form pores in its membrane. These newly formed pores allow access by granzymes, proteases that initiate a sequence of events that will ultimately kill the target cell (see Figure 23-6). This process, called antibody-dependent cell-mediated cytotoxicity (ADCC), illustrates how cells of the innate immune system interact with, and benefit from, the products of the adaptive immune response.

Antigen-antibody (immune) complexes of some immunoglobulin isotypes can initiate the classical pathway of complement activation (see Figure 23-5). IgM and IgG3 are particularly good at complement activation, but all IgG classes can, in principle, activate complement, whereas IgA and IgE are unable to do so. The large amounts of IgA found in the gut contribute to its barrier function by neutralizing gut-resident microbes.

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