Immunology is a relatively new science. Its origin is usually attributed to Edward Jenner (Fig. 1.1), who discovered in 1796 that cowpox, or vaccinia, induced protection against human smallpox, an often fatal disease. Jenner called his procedure vaccination, and this term is still used to describe the inoculation of healthy individuals with weakened or attenuated strains of disease-causing agents to provide protection from disease. Although Jenner's bold experiment was successful, it took almost two centuries for smallpox vaccination to become universal, an advance that enabled the World Health Organization to announce in 1979 that smallpox had been eradicated (Fig. 1.2), arguably the greatest triumph of modern medicine.

Figure 1.1

Edward Jenner. Portrait by John Raphael Smith. Reproduced courtesy of Yale University, Harvey Cushing/John Hay Whitney Medical Library.

Figure 1.2

The eradication of smallpox by vaccination. After a period of 3 years in which no cases of smallpox were recorded, the World Health Organization was able to announce in 1979 that smallpox had been eradicated.

When Jenner introduced vaccination he knew nothing of the infectious agents that cause disease: it was not until late in the 19th century that Robert Koch proved that infectious diseases are caused by microorganisms, each one responsible for a particular disease, or pathology. We now recognize four broad categories of disease-causing microorganisms, or pathogens: these are viruses, bacteria, pathogenic fungi, and other relatively large and complex eukaryotic organisms collectively termed parasites.

The discoveries of Koch and other great 19th century microbiologists stimulated the extension of Jenner's strategy of vaccination to other diseases. In the 1880s, Louis Pasteur devised a vaccine against cholera in chickens, and developed a rabies vaccine that proved a spectacular success upon its first trial in a boy bitten by a rabid dog. These practical triumphs led to a search for the mechanism of protection and to the development of the science of immunology. In 1890, Emil von Behring and Shibasaburo Kitasato discovered that the serum of vaccinated individuals contained substances—which they called antibodies—that specifically bound to the relevant pathogen.

A specific immune response, such as the production of antibodies against a particular pathogen, is known as an adaptive immune response, because it occurs during the lifetime of an individual as an adaptation to infection with that pathogen. In many cases, an adaptive immune response confers lifelong protective immunity to reinfection with the same pathogen. This distinguishes such responses from innate immunity, which, at the time that von Behring and Kitasato discovered antibodies, was known chiefly through the work of the great Russian immunologist Elie Metchnikoff. Metchnikoff discovered that many microorganisms could be engulfed and digested by phagocytic cells, which he called macrophages. These cells are immediately available to combat a wide range of pathogens without requiring prior exposure and are a key component of the innate immune system. Antibodies, by contrast, are produced only after infection, and are specific for the infecting pathogen. The antibodies present in a given person therefore directly reflect the infections to which he or she has been exposed.

Indeed, it quickly became clear that specific antibodies can be induced against a vast range of substances. Such substances are known as antigens because they can stimulate the generation of antibodies. We shall see, however, that not all adaptive immune responses entail the production of antibodies, and the term antigen is now used in a broader sense to describe any substance that can be recognized by the adaptive immune system.

Both innate immunity and adaptive immune responses depend upon the activities of white blood cells, or leukocytes. Innate immunity largely involves granulocytes and macrophages. Granulocytes, also called polymorphonuclear leukocytes, are a diverse collection of white blood cells whose prominent granules give them their characteristic staining patterns; they include the neutrophils, which are phagocytic. The macrophages of humans and other vertebrates are presumed to be the direct evolutionary descendants of the phagocytic cells present in simpler animals, such as those that Metchnikoff observed in sea stars. Adaptive immune responses depend upon lymphocytes, which provide the lifelong immunity that can follow exposure to disease or vaccination. The innate and adaptive immune systems together provide a remarkably effective defense system. It ensures that although we spend our lives surrounded by potentially pathogenic microorganisms, we become ill only relatively rarely. Many infections are handled successfully by the innate immune system and cause no disease; others that cannot be resolved by innate immunity trigger adaptive immunity and are then overcome successfully, followed by lasting immunological memory.

The main focus of this book will be on the diverse mechanisms of adaptive immunity, whereby specialized classes of lymphocytes recognize and target pathogenic microorganisms or the cells infected with them. We shall see, however, that all the cells involved in innate immune responses also participate in adaptive immune responses. Indeed, most of the effector actions that the adaptive immune system uses to destroy invading microorganisms depend upon linking antigen-specific recognition to the activation of effector mechanisms that are also used in innate host defense.

In this chapter, we first introduce the cells of the immune system, and the tissues in which they develop and through which they circulate or migrate. In later sections, we outline the specialized functions of the different types of cells and the mechanisms by which they eliminate infection.

Contents

• The components of the immune system
• Principles of innate and adaptive immunity
• The recognition and effector mechanisms of adaptive immunity
• Summary to Chapter 1
• General references