The main function of our immune system is to protect the human host from infectious agents. However, many medically important diseases are associated with a normal immune response directed against an inappropriate antigen, often in the absence of infectious disease. Immune responses directed at noninfectious antigens occur in allergy, in which the antigen is an innocuous foreign substance; in autoimmune disease, in which the response is to a self antigen; and in graft rejection, in which the antigen is borne by a transplanted foreign cell (discussed in Chapter 15). The major antigens provoking graft rejection are, in fact, the MHC molecules, as each of these is present in many different versions in the human population—that is, they are highly polymorphic—and most unrelated people differ in the set of MHC molecules they express, a property commonly known as their ‘tissue type.’ The MHC was originally recognized by the work of Peter Goren in the 1930s as a gene locus in mice, the H-2 locus, that controlled the acceptance or rejection of transplanted tumors, and later by George Snell, who examined their role in tissue transplantation by developing mouse strains differing only at these histocompatibility loci. The human MHC molecules were first discovered during the Second World War, when attempts were made to use skin grafts from donors to repair badly burned pilots and bomb victims. The patients rejected the grafts, which were recognized by their immune systems as being ‘foreign.’ What we call a successful immune response or a failure, and whether the response is considered harmful or beneficial to the host, depends not on the response itself but rather on the nature of the antigen and the circumstances in which the response occurs (Fig. 1.35). Snell was awarded the 1980 Nobel Prize for his work on MHC, together with Baruj Benacerraf and Jean Dausset.
Allergic diseases, which include asthma, are an increasingly common cause of disability in the developed world. Autoimmunity is also now recognized as the cause of many important diseases. An autoimmune response directed against pancreatic β cells is the leading cause of diabetes in the young. In allergies and autoimmune diseases, the powerful protective mechanisms of the adaptive immune response cause serious damage to the patient.
Immune responses to harmless antigens, to body tissues, or to organ grafts are, like all other immune responses, highly specific. At present, the usual way to treat these responses is with immunosuppressive drugs, which inhibit all the effector mechanisms of immunity.
immune responses, desirable and undesirable alike. If it were possible to suppress only those lymphocyte clones responsible for the unwanted response, the disease could be cured or the grafted organ protected without impeding protective immune responses. At present, antigen-specific immunoregulation is outside the reach of clinical treatment. But as we shall see in Chapter 16, many new drugs have been developed recently that offer more selective immune suppression to control autoimmune and other unwanted immune responses. Among these, therapies using highly specific monoclonal antibodies were made possible by Georges Köhler and César Milstein, who shared the 1984 Nobel Prize for the discovery of their production. We shall discuss the present state of understanding of allergies, autoimmune disease, graft rejection, and immunosuppressive drugs and monoclonal antibodies in Chapters 14–16, and we shall see in Chapter 15 how the mechanisms of immune regulation are beginning to emerge from a better understanding of the functional subsets of lymphocytes and the cytokines that control them.
1-24 Vaccination is the most effective means of controlling infectious diseases.