The unique and characteristic pocket on an antibody that recognizes a specific antigen-its variable region-can itself act as an antigen. More precisely, the variable region contains a number of antigen-like segments, and these are known collectively as an idiotype. Like any other antigen, an idiotype can trigger complementary antibody. This second-round antibody is known as an antiidiotype. An antiidiotype, in turn, can trigger an antiantiidiotype. Like a series of mirrored reflections, the process can go on and on.

Interactions between idiotypes and antiidiotypes, it has been proposed, constitute a mechanism whereby the immune system regulates itself. According to the "network theory," not only antibodies but B cells and T cells carry-in their unique antigen-receptors-idiotypes. The B cells and T cells that proliferate in response to a certain antigen carry a complementary idiotype. Antiidiotype B cells secrete antiidiotype antibodies, which may neutralize the original idiotypes (antibodies), or bind to idiotypes on regulatory T cells. Alternatively, antiidiotypes may trigger antiantiidiotypes, creating a spiraling response within the network-turning on, amplifying, and shutting down immune responses.

The concept of the idiotype is being put to practical use today in the development of experimental antigen-free vaccines (Vaccines Through Biotechnology).

Microbes that breach the nonspecific barriers are confronted by specific weapons tailored to fit each one. These may be cellular responses directed both by cells, primarily T lymphocytes and their secretions (lymphokines), and against cells that have been infected. Or they may be humoral responses, the work of antibodies secreted by B lymphocytes into the body's fluids or humors.

Most antigens are recognized by a limited number of specific immune cells ( and their offspring). A few antigens, however, are capable of rousing large classes of T cells, setting off an immune response so massive that it is harmful. Dubbed "superantigens," these substances include bacterial toxins such as those responsible for the toxic shock syndrome.

Although immunologists traditionally distinguished between cellular and humoral immunity, it has become increasingly clear that the two arms of the immune response are closely intertwined. Almost all antigens evoke both a humoral response and a cellular response-and most B cell responses require T cell help. In practice, however, one arm is usually more effective than the other, and regulatory mechanisms end up skewing the response toward either the cellular or the humoral side.

The cell-mediated response is initiated by a macrophage or other antigen-presenting cell. The antigen-presenting cell takes in the antigen, digests it, and then displays antigen fragments on its own surface. Bound to the antigen fragment is an MHC molecule. It takes both of these structures, together, to capture the T cell's attention.

A T cell whose receptor fits this antigen-MHC complex binds to it. The binding stimulates the antigen-presenting cell to secrete interleukins required for T cell activation and performance.

Before activated T cells can set to work, however, they need a second go-ahead signal. In a maneuver known as co-stimulation, the antigen-presenting cell displays a special molecule that engages specific receptor molecules on the T cell, including one known as CD28. Without co-stimulation, activated T cells fall into a state of unresponsiveness known as anergy. Anergy arrests T cell growth by blocking its ability to produce or respond to signals to proliferate.

Once up and going, some subsets of T cells synthesize and secrete lymphokines. Interleukin-2, for instance, spurs the growth of more T cells. Other lymphokines attract other immune cells-fresh macrophages, granulocytes, and other lymphocytes-to the site of the infection. Yet others direct the cells' activities once they arrive on the scene. Some subsets of T cells become killer (or cytotoxic) cells, and set out to track down body cells infected by viruses. And when the infection has been brought under control, suppressor T cells draw the immune response to a close.