The Adaptive Immune System (2024)

Our adaptive immune system saves us from certain death by infection. An infant born with a severely defective adaptive immune system will soon die unless extraordinary measures are taken to isolate it from a host of infectious agents, including bacteria, viruses, fungi, and parasites. Indeed, all multicellular organisms need to defend themselves against infection by such potentially harmful invaders, collectively called pathogens. Invertebrates use relatively simple defense strategies that rely chiefly on protective barriers, toxic molecules, and phagocytic cells that ingest and destroy invading microorganisms (microbes) and larger parasites (such as worms). Vertebrates, too, depend on such innate immune responses as a first line of defense (discussed in Chapter 25), but they can also mount much more sophisticated defenses, called adaptive immune responses. The innate responses call the adaptive immune responses into play, and both work together to eliminate the pathogens (Figure 24-1). Unlike innate immune responses, the adaptive responses are highly specific to the particular pathogen that induced them. They can also provide long-lasting protection. A person who recovers from measles, for example, is protected for life against measles by the adaptive immune system, although not against other common viruses, such as those that cause mumps or chickenpox. In this chapter, we focus mainly on adaptive immune responses, and, unless we indicate otherwise, the term immune responses refers to them. We discuss innate immune responses in detail in Chapter 25.

The function of adaptive immune responses is to destroy invading pathogens and any toxic molecules they produce. Because these responses are destructive, it is crucial that they be made only in response to molecules that are foreign to the host and not to the molecules of the host itself. The ability to distinguish what is foreign from what is self in this way is a fundamental feature of the adaptive immune system. Occasionally, the system fails to make this distinction and reacts destructively against the host's own molecules. Such autoimmune diseases can be fatal.

Of course, many foreign molecules that enter the body are harmless, and it would be pointless and potentially dangerous to mount adaptive immune responses against them. Allergic conditions such as hayfever and asthma are examples of deleterious adaptive immune responses against apparently harmless foreign molecules. Such inappropriate responses are normally avoided because the innate immune system calls adaptive immune responses into play only when it recognizes molecules characteristic of invading pathogens called pathogen-associated immunostimulants (discussed in Chapter 25). Moreover, the innate immune system can distinguish between different classes of pathogens and recruit the most effective form of adaptive immune response to eliminate them.

Any substance capable of eliciting an adaptive immune response is referred to as an antigen(antibody generator). Most of what we know about such responses has come from studies in which an experimenter tricks the adaptive immune system of a laboratory animal (usually a mouse) into responding to a harmless foreign molecule, such as a foreign protein. The trick involves injecting the harmless molecule together with immunostimulants (usually microbial in origin) called adjuvants, which activate the innate immune system. This process is called immunization. If administered in this way, almost any macromolecule, as long as it is foreign to the recipient, can induce an adaptive immune response that is specific to the administered macromolecule. Remarkably, the adaptive immune system can distinguish between antigens that are very similar—such as between two proteins that differ in only a single amino acid, or between two optical isomers of the same molecule.

Adaptive immune responses are carried out by white blood cells called lymphocytes. There are two broad classes of such responses—antibody responses and cell-mediated immune responses, and they are carried out by different classes of lymphocytes, called B cells and T cells, respectively. In antibody responses, B cells are activated to secrete antibodies, which are proteins called immunoglobulins. The antibodies circulate in the bloodstream and permeate the other body fluids, where they bind specifically to the foreign antigen that stimulated their production (Figure 24-2). Binding of antibody inactivates viruses and microbial toxins (such as tetanus toxin or diphtheria toxin) by blocking their ability to bind to receptors on host cells. Antibody binding also marks invading pathogens for destruction, mainly by making it easier for phagocytic cells of the innate immune system to ingest them.

In cell-mediated immune responses, the second class of adaptive immune response, activated T cells react directly against a foreign antigen that is presented to them on the surface of a host cell. The T cell, for example, might kill a virus-infected host cell that has viral antigens on its surface, thereby eliminating the infected cell before the virus has had a chance to replicate (see Figure 24-2). In other cases, the T cell produces signal molecules that activate macrophages to destroy the invading microbes that they have phagocytosed.

We begin this chapter by discussing the general properties of lymphocytes. We then consider the functional and structural features of antibodies that enable them to recognize and neutralize extracellular microbes and the toxins they make. Next, we discuss how B cells can produce a virtually unlimited number of different antibody molecules. Finally, we consider the special features of T cells and the cell-mediated immune responses they are responsible for. Remarkably, T cells can detect microbes hiding inside host cells and either kill the infected cells or help other cells to eliminate the microbes.