Immunology. Richard Coico
Anyone who has had the good fortune to hear an orchestra brilliantly perform a symphony composed by one of the great masters knows that each of the carefully tuned musical instruments contributes to the collective, harmonious sound produced by the musicians. In many ways, the normally tuned immune system continuously plays an orchestrated symphony to maintain homeostasis in the context of host defenses. However, as William Shakespeare noted, “Untune that string, and, hark, what discord follows!” (Troilus and Cressida). Similarly, an untuned immune system can cause discord, which manifests as autoimmunity, cancer, or chronic inflammation. Fortunately for most of us, our immune system is steadfastly vigilant in regard to tuning (regulating) itself to ensure that its cellular components behave and interact symbiotically to generate protective immune responses that ensure good health. In many ways the immune system can be described in anthropomorphic terms: its memory allows it to remember and recognize pathogens years or decades after initial exposure; it can distinguish between the body’s own cells and those of another organism; and it makes decisions about how to respond to particular pathogens—including whether or not to respond at all, as will be discussed in later chapters.
In his penetrating essays, scientist–author Lewis Thomas, discussing symbiosis and parasitism, described the forces that would drive all living matter into one huge ball of protoplasm were it not for regulatory and recognition mechanisms that allow us to distinguish self from nonself. The origins of these mechanisms go far back in evolutionary history, and many, in fact, originated as markers for allowing cells to recognize and interact with each other to set up symbiotic households. Genetically related sponge colonies that are placed close to each other, for example, will tend to grow toward each other and fuse into one large colony. Unrelated colonies, however, will react in a different way, destroying cells that come in contact with each other and leaving a zone of rejection between the colonies.
In the plant kingdom, similar types of recognition occur. In self‐pollinating species, a pollen grain landing on the stigma of a genetically related flower will send a pollen tubule down the style to the ovary for fertilization. A pollen grain from a genetically distinct plant either will not germinate or the pollen tubule, once formed, will disintegrate in the style. The opposite occurs in cross‐pollinating species: self‐marked pollen grains disintegrate, whereas nonself grains germinate and fertilize.
The nature of these primitive recognition mechanisms has not been completely worked out, but almost certainly it involves cell‐surface molecules that are able to specifically bind and adhere to other molecules on opposing cell surfaces. This simple method of molecular recognition has evolved over time into the very complex immune system that retains, as its essential feature, the ability of a protein molecule to recognize and bind specifically to a particular shaped structure on another molecule. Such molecular recognition is the underlying principle involved in the discrimination between self and nonself during an immune response. It is the purpose of this book to describe the mammalian immune system which has evolved from this simple beginning which makes use of this principle of recognition in increasingly complex and sophisticated ways.
Perhaps the greatest catalyst for progress in this and many other biomedical areas has been the advent of molecular biologic techniques. It is important to acknowledge, however, that certain technological advances in the field of molecular biology were made possible by earlier progress in the field of immunology. For example, the importance of immunologic methods (see Chapter 20) used to purify proteins as well as identify specific cDNA clones cannot be overstated. These advances were greatly facilitated by the pioneering studies of Köhler and Milstein (1975), who developed a method for producing monoclonal antibodies. Their achievement was rewarded with the Nobel Prize in Medicine. It revolutionized research efforts in virtually all areas of biomedical science. Some monoclonal antibodies produced against so‐called tumor‐specific antigens have now been approved by the US Food and Drug Administration for use in patients to treat certain malignancies. Monoclonal antibody technology is, perhaps, one of the best examples of how the science of immunology has transformed not only the field of medicine but also fields ranging from agriculture to the food science industry.
Given the rapid advances occurring in immunology and the many other biomedical sciences and, perhaps most important, the sequencing of the human genome, every contemporary biomedical science textbook runs a considerable risk of being outdated before it appears in print. Nevertheless, we take solace from the observation that new formulations generally build on and expand the old rather than replacing or negating them completely. Let’s begin, therefore, with an overview of innate and adaptive immunity (also called acquired immunity) which continue to serve as a conceptual compass that orients our fundamental understanding of host defense mechanisms.
INNATE AND ADAPTIVE IMMUNITY
The Latin term immunis, meaning “exempt,” gave rise to the English word immunity, which refers to all the mechanisms used by the body as protection against environmental agents that are foreign to the body. These agents may be microorganisms or their products, foods, chemicals, drugs, pollen, or animal hair and dander.
Our understanding of how the innate and adaptive immune systems interact to enable host immune responses to optimally protect the host from infectious pathogens is greatly enhanced by our knowledge of the cells and tissues of the immune system at large (see Chapter 3). Below is a brief overview of the innate and adaptive immune systems followed by an introduction to the development of the immune system.
Innate Immunity
Innate immunity is conferred by all those elements with which an individual is born and that are always present and available at very short notice to protect the individual from challenges by foreign invaders. The major properties of the innate immune system are discussed in Chapter 3. Table 1.1 summarizes and compares some of the features of the innate and adaptive immune systems. Elements of the innate system include body surfaces and internal components, such as the skin, the mucous membranes, and the cough reflex, which present effective barriers to environmental agents. Chemical influences, such as pH and secreted fatty acids, constitute effective barriers against invasion by many microorganisms. Another noncellular element of the innate immune system is the complement system. As in the previous editions of this book, we cover the subject of complement in Chapter 4.
Numerous other components are also features of innate immunity: fever, interferons, other substances released by leukocytes, and pattern recognition molecules (innate receptors), which can bind to various microorganisms (e.g., Toll‐like receptors or TLRs; see Chapter 3), as well as serum proteins such as β‐lysin, the enzyme lysozyme, polyamines, and the kinins, among others. All of these elements either affect pathogenic invaders directly or enhance the effectiveness of host reactions to them. Other internal elements of innate immunity include phagocytic cells such as granulocytes, macrophages, and microglial cells of the central nervous system, which participate in the destruction and elimination of foreign material that has penetrated the physical and chemical barriers.
TABLE 1.1. Major Properties of the Innate and Adaptive Immune Systems
| Property | Innate | Adaptive |
|---|---|---|
| Characteristics | Antigen nonspecific | Antigen specific |
| Rapid response (minutes to hours) | Slow response (days) | |