Adaptive immune responses develop in several steps, starting with the capture of antigen, followed by the activation of specific lymphocytes (Fig. 1).
Fig1. Development of adaptive immune responses. Adaptive immune responses consist of distinct steps, the first three being the recognition of antigen, the activation of lymphocytes, and the elimination of the antigen (the effector phase). The response contracts (declines) as antigen-stimulated lymphocytes die by apoptosis, restoring homeostasis, but many antigen-specific cells survive for a long time and differentiate into memory cells. The duration of each phase may vary in different immune responses. The y-axis represents an arbitrary measure of the magnitude of the response. These principles apply to humoral immunity (mediated by B lymphocytes) and cell-mediated immunity (mediated by T lymphocytes).
Most microbes and other antigens enter through epithelial barriers and may colonize tissues, and adaptive immune responses to these antigens develop in secondary (peripheral) lymphoid organs. The initiation of adaptive immune responses requires that antigens be captured and displayed to specific lymphocytes. The cells that serve this role are called antigen-presenting cells (APCs). The most specialized APCs are dendritic cells (DCs), which capture microbial antigens that enter from the external environment, transport these antigens to secondary lymphoid organs called lymph nodes, and present the antigens to naive T lymphocytes to initiate immune responses. Cells other than DCs may function as APCs at different stages of cell-mediated and humoral immune responses. We will describe lymph nodes in Chapter 2 and the functions of APCs in Chapter 6.
Naive lymphocytes express antigen receptors but have not responded to antigen. The activation of these lymphocytes by an antigen leads to the proliferation of these cells, resulting in an increase in the number of lymphocytes with identical antigen receptors. The population of lymphocytes derived from a single naive lymphocyte is called a clone. In response to antigen recognition (and other signals discussed in later chapters), lymphocytes proliferate, leading to an increase in the clone, a process called clonal expansion. Concurrent with clonal expansion is the differentiation of the antigen-stimulated lymphocytes into cells capable of eliminating the antigen, called effector cells because they mediate the ultimate effect of the immune response, and the differentiation of some of the activated lymphocytes into memory cells that survive for long periods and mount strong responses upon repeat antigen encounter. Antigen elimination often requires the participation of other, nonlymphoid cells, such as macrophages and neutrophils, which are also sometimes called effector cells. These steps in lymphocyte activation and differentiation into effector cells typically take several days, which explains why the adaptive response is slow to develop and innate immunity has to provide protection initially.
After the adaptive immune response has eradicated the infection, the stimuli for lymphocyte activation dissipate and most of the effector cells die, resulting in the decline of the response. Memory cells remain, ready to respond vigorously if the same infection recurs.
The cells of the immune system interact with one another and with other host cells via secreted proteins called cytokines. Such interactions are essential during both the initiation and effector stages of innate and adaptive immune responses. Cytokines are a large group of secreted proteins with diverse structures and functions, which regulate and coordinate many activities of the cells of innate and adaptive immunity. All cells of the immune system secrete at least some cytokines and express specific signaling receptors for several cytokines. Some of the many functions of cytokines we will discuss throughout this book include promoting the growth and differentiation of immune cells, activating the functions of lymphocytes and phagocytes that eliminate microbes (called effector functions), and stimulating directed movement of immune cells from blood into tissues and within tissues. A large subset of structurally related cytokines that regulate cell adhesion and migration are called chemokines. Cytokines are also involved in immunological diseases, and some of the most effective drugs developed to treat these diseases target cytokines.
