The Immune Response All organisms are continually subject to attack by other pathogenic organisms. In defense against attack by disease-causing microorganisms and viruses (pathogens), animals have evolved an elaborate protective array known as the immune system. Pathogens that manage to breach the physical barrier presented by skin and mucous membranes are identified as foreign invaders and destroyed. Immunity in vertebrates is conferred by lymphocytes. Lymphocytes are white blood cells, which, in contrast to red blood cells, can leave the blood vessels and patrol intercellular spaces for foreign pathogens.

Protective Mechanisms in the Immune System Two types of immunity have been characterized. Cellular immunity guards against virally-infected cells and is mediated by T lymphocytes (T cells). Humoral immunity is mediated by a diverse collection of proteins known as antibodies. These proteins protect against bacterial and viral infections.

Figure 1. (a) Cartoon representation of IgG2a. There are two heavy chains (red) and two identical light chains (blue). (b) Diagram of an IgG molecule (Harris et al, 1997).

Figure 2. Conversion of an inactive B cell to its active non-antibody producing form (Elliot, W.H., 1997).

The Cellular Immune System The immune response is triggered by the presence of foreign macromolecules known as antigens (normally proteins, carbohydrates and nucleic acids). The cellular immune response occurs through a complex series of interactions involving T cells and B cells, leading to the destruction of the antigen.

The Humoral Immune System B cells display both IgG’s and Class II MHC proteins on their surfaces. If a B cell encounters an antigen that binds to its particular IgG, it engulfs the complex, partially digests the antigen and displays the fragments on its surface in complex with the Class II MHC protein. Mature helper T cells, bearing receptors specific for this complex, bind to the B cell and release interleukins that stimulate B cell proliferation and differentiation. B cell proliferation continues so long as B cells are stimulated by helper T cells in the presence of an antigen. Most B cell progeny are specialized to secrete large amounts of antigen-specific antibody. The secreted antibodies bind to antigen, marking it for destruction either by phagocytosis or cell lyses (Davies et al 1990).

Figure 3. Diagram of a helper T cell activating a B cell for clonal selection (Elliot, W.H., 1997).

The Cellular Immune System and Immunosuppresion The cellular immune system is responsible for various complications of modern therapies. The cellular immune system functions to prevent the spread of a viral infection by killing virus-infected host cells. However, tissue transplants or organ grafts from donors are almost always recognized as foreign. These foreign tissues bear MHC proteins that differ from those of the host and are targeted by the cellular immune response. Such grafts and tissue transplants have only been made possible by the development of drugs known as immunosuppressants which partially or completely suppress a patients immune response (Thomson, G., 1998).

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This process is further enhanced by the T cells’ auto-stimulatory secretion of interleukin-2 (IL-2). A large number of mature cytotoxic T cells specifically targeted for host cells displaying both the foreign antigen and Class 1 MHC proteins are generated in response to IL-2 (Englehard, V.H., 1994). The cytotoxic T cells bind to antigen-bearing host cells and lyses these target cells (Podack et al, 1991).
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