or indirect (immune system targeted) therapy. It is noteworthy that the Nobel Prize was awarded in 1984 to Köhler and Milstein for their technological advances in the development of monoclonal antibodies and them in 2018, James Allison was awarded the Nobel Prize for launching an effective new way to attack cancer by treating the immune system rather than the tumor.
The innate and adaptive immune systems play an integral role in the prevention of and recovery from infectious diseases and are, without question, essential to the survival of the individual. Metchnikoff was the first to propose in the 1800s that phagocytic cells formed the first line of defense against infection and that the inflammatory response could actually serve a protective function for the host. Indeed, innate immune responses are responsible for the detection and rapid destruction of most infectious agents that are encountered in the daily lives of most individuals. We now know that innate immune responses operate in concert with adaptive immune responses to generate antigen‐specific effector mechanisms that lead to the death and elimination of the invading pathogen. Chapter 19 presents information concerning how our immune systems respond to microorganisms and how methods developed to exploit these mechanisms are used as immunoprophylaxis.
Vaccination against infectious diseases has been an effective form of prophylaxis. Immunoprophylaxis against the virus that causes poliomyelitis has significantly reduced the incidence of this dreadful disease. Indeed, the previously widespread disease smallpox has been eliminated from the face of the Earth. The last documented case of natural transmission of smallpox virus was in 1972. Unfortunately, the threat of biological weapons has prompted new concerns regarding the reemergence of certain infectious diseases, including smallpox. Fortunately, public health vaccination initiatives can be applied to prevent or significantly curtail the threat of weaponized microbiological agents.
DAMAGING EFFECTS OF THE IMMUNE RESPONSE
The enormous survival value of the immune response is self‐evident. Adaptive immunity directed against a foreign material has as its ultimate goal the elimination of the invading substance. In the process, some tissue damage may occur as a result of the accumulation of components with nonspecific effects. This damage is generally temporary. As soon as the invader is eliminated, the situation at that site reverts to normal.
There are instances in which the power of the immune response, although directed against foreign substances—some innocuous such as some medications, inhaled pollen particles, or substances deposited by insect bites—produces a response that may result in severe pathological consequences and even death. These responses are known collectively as hypersensitivity reactions or allergic reactions. An understanding of the basic mechanisms underlying these disease processes has been fundamental in their treatment and control and, in addition, has contributed much to our knowledge of the normal immune response. The latter is true because both utilize essentially identical mechanisms; however, in hypersensitivity, these mechanisms are misdirected or out of control (see Chapters ).
Given the complexity of the immune response and its potential for inducing damage, it is self‐evident that it must operate under carefully regulated conditions, as does any other physiological system. These controls are multiple and include feedback inhibition by soluble products as well as cell–cell interactions of many types, which may either heighten or reduce the response. The net result is to maintain a state of homeostasis so that when the system is perturbed by a foreign invader, enough response is generated to control the invader, and then the system returns to equilibrium; in other words, the immune response is shut down. However, its memory of that particular invader is retained so that a more rapid and heightened response will occur should the invader return.
Disturbances in these regulatory mechanisms may be caused by conditions such as congenital defects, hormonal imbalance, or infection, any of which can have disastrous consequences. AIDS may serve as a timely example: it is associated with an infection of T lymphocytes that participate in regulating the immune response. As a result of infection with the human immunodeficiency virus (HIV), which causes AIDS, there is a decrease in occurrence and function of one vital subpopulation of T cells, which leads to immunological deficiency and renders the patient powerless to resist infections by microorganisms that are normally benign. An important form of regulation concerns the prevention of immune responses against self‐antigens. As discussed in Chapter 12, this regulation may be defective, thus causing an immune response against self to be mounted. This type of immune response is termed autoimmunity and is the cause of diseases such as some forms of arthritis, thyroiditis, and diabetes, which are very difficult to treat.
THE FUTURE OF IMMUNOLOGY
For the student, a peek into the world of the future of immunology suggests many exciting areas in which the application of molecular and computational techniques promises significant dividends. To cite just a few examples, let us focus on vaccine development and control of the immune response. In the former, rather than the laborious, empirical search for an attenuated virus or bacterium for use in immunization, it is now possible to use pathogen‐specific protein sequence data and sophisticated computational methods (bioinformatics) to identify candidate immunogenic peptides that can be tested as vaccines. Alternatively, DNA vaccines involving the injection of DNA vectors that encode immunizing proteins may revolutionize vaccination protocols in the not too distant future. The identification of various genes and the proteins or portions thereof (peptides) that they are encoding makes it possible to design vaccines against a wide spectrum of biologically important compounds.
Another area of great promise is the characterization and synthesis of cytokines that enhance and control the activation of various cells associated with the immune response as well as with other functions of the body. Techniques of gene isolation, clonal reproduction, the polymerase chain reaction, and biosynthesis have contributed to rapid progress. Powerful and important modulators have been synthesized by the methods of recombinant DNA technology and are being tested for their therapeutic efficacy in a variety of diseases, including many different cancers. In some cases, cytokine research efforts have already moved from the bench to the bedside with the development of therapeutic agents used to treat patients.
Finally, and probably one of the most exciting areas, is the technology to genetically engineer cells and even whole animals, such as mice, that lack one or more specific traits (gene knockout) or that carry a specific trait (transgenic). These and other immune‐based experimental systems are the subject of the final chapter (Chapter 20). They allow the immunologist to study the effects of such traits on the immune system and on the body as a whole with the aim of understanding the intricate regulation, expression, and function of the immune response, and with the ultimate aim of controlling the trait to the benefit of the individual. Thus our burgeoning understanding of the functioning of the immune system, combined with the recently acquired ability to alter and manipulate its components, carries enormous implications for the future of humankind.
THE SHORT COURSE BEGINS HERE
This brief overview of the immune system is intended to orient the reader about the complex yet fascinating subject of immunology. In the following chapters we provide a more detailed account of the workings of the immune system, beginning with its cellular components, followed by a description of the structure of the reactants and the general methodology for measuring their reactions. This is followed by chapters describing the formation and activation of the cellular and molecular components of the immune apparatus required to generate a response. A discussion of the control mechanisms that regulate the scope and intensity of immune responses completes the description of the basic nature of immunity. Included in this section of the book is a chapter on cytokines (Chapter 11), the soluble mediators that
