Basic Components of the Immune System
It is generally believed that the immune system evolved as the host’s defense against infectious agents, and it is well known that patients with deficiencies in the immune system generally succumb to these infectious diseases. However, as we shall see, it may well play a larger role in the elimina-tion of other foreign substances, including tumor antigens or cells and antibodies that attack self.
An immune response may be conve-niently divided into two parts: (1) a specific response to a given antigen and (2) a more nonspecific augmentation to that response. An important feature of the specific response is that there is a quicker response to the antigen during a second exposure to that antigen. It is the memory of the initial response that provides the booster effect.
For convenience, the specific immune response may be divided into two parts:
(1) the humoral response and (2) the cellu-lar response to a given antigen. As we shall see, however, both responses are medi-ated through the lymphocyte. Humoral responses are antibodies produced in response to a given antigen, and these anti-bodies are proteins, have similar structures, and can be divided into various classes of immunoglobulins. Cellular responses are established by cells and can only be trans-ferred by cells. (See the Bibliography for the extraordinary beginnings of the con-cept of a cellular arm of the immune sys-tem.) Up to the 1940s the general dogma held that only antibodies were involved in the immune response. Dr. Merrill Chase, who began his experiments in a labora-tory devoted primarily to the humoral response, clearly showed in a series of ele-gant experiments that immunity was not just humoral but that a cellular response by the lymphocytes could also produce immunity. Some of the best examples of the power of cellular immunity may be found in the many experiments in which transfer of cells can induce autoimmune disease in animals and humans as well as rejection of an organ graft in both animals and humans by cells.
The separation of human and cellular immunity was further advanced by the study of immunodeficient humans and animals. For example, thymectomized or congenitally athymic animals as well as humans cannot carry out graft rejection, yet they are capable of producing some antibody responses. The reverse is also true. Children (and animals) who have an immune deficit in the humoral response do not make antibodies but can reject
grafts and appear to handle viral, fungal, and some bacterial infections quite well. An extraordinary finding by Good and colleagues in studying the cloacal lym-phoid organ in chickens revealed that, with removal of the bursa Fabricius, these animals lost their ability to produce anti-bodies and yet retained the ability to reject grafts.
Out of these and many other contribu-tions, a clearer picture of the division of efforts by lymphocytes begins to emerge. Since cellular immune responses require an intact thymus, cellular immune responses are mediated through the T lymphocytes (thymus), while antibody-producing cells, which are dependent on the bone mar-row (the bursa equivalent), are known as B (bursa) cells. The pathways of both cell types are depicted in Figure 1.1.
Figure 1.1 Development and differentiation of lymphocytes from pluripotential stem cells.
Several types of molecules play a vital role in the immune response, and we will deal with each in detail. Antigens, both foreign and self, are substances that may or may not provoke an immune response. Both T cells and B cells have receptors that recognize these antigens. In the case of B cells, antibodies on the surface are a major source (but not the only one) of antigen recognition, and once activated, they differen-tiate into plasma cells that produce large quantities of antibodies that are secreted into blood and body fluids to block the harmful effects of the antigen.
T cells have similar receptors known as T-cell receptors (TCR), and in the con-text of the major histocompatibility complex (MHC) molecules provide a means of self-recognition and T-lymphocyte effector functions. Often these effector functions are carried out by messages transmitted between these cells. These soluble messen-gers are called interleukins or cytokines.