stimulating the response is complex and contains many different epitopes, each capable of activating a clone of epitope‐specific B cells. Hence, collectively, the clonally secreted antibodies constitute what is often referred to as polyclonal antiserum, which is capable of interacting with the multiple epitopes expressed by the antigen.
T cells are similarly selected by appropriate epitopes or portions thereof. Each selected T cell will be activated to divide and produce clones of the same specificity. Thus the clonal response to the antigen will be amplified, the cells will release various cytokines, and subsequent exposure to the same antigen will now result in the activation of many cells or clones of that specificity. Instead of synthesizing and releasing antibodies like the B cells, the T cells synthesize and release cytokines. These cytokines, which are soluble mediators, exert their effect on other cells to grow or become activated, facilitating elimination of the antigen. Several distinct regions of an antigen (epitopes) can be recognized: several different clones of B cells will be stimulated to produce antibody, whose sum total is an antigen‐specific antiserum that is made up of antibodies of differing specificity (see Figure 1.1); all the T‐cell clones that recognize various epitopes on the same antigen will be activated to perform their function.
A final postulate was added to account for the ability to recognize self‐antigens without making a response.
Circulating self‐antigens that reach the developing lymphoid system before some undesignated maturational step will serve to shut off those cells that recognize it specifically, and no subsequent immune response will be induced.
ACTIVE, PASSIVE, AND ADOPTIVE IMMUNIZATION
Adaptive immunity is induced by immunization, which can be achieved in several ways.
Active immunization refers to immunization of an individual by administration of an antigen.
Passive immunization refers to immunization through the transfer of specific antibody from an immunized individual to a nonimmunized individual.
Adoptive immunization refers to the transfer of immunity by the transfer of immune cells.
Major Characteristics of the Adaptive Immune Response
The adaptive immune response has several generalized features that characterize it and distinguish it from other physiological systems, such as circulation, respiration, and reproduction. These features are as follows.
Specificity is the ability to discriminate among different molecular entities and to respond only to those uniquely required, rather than making a random, undifferentiated response.
Adaptiveness is the ability to respond to previously unseen molecules that may in fact never have naturally existed before on Earth.
Discrimination between self and nonself is a cardinal feature of the specificity of the immune response; it is the ability to recognize and respond to molecules that are foreign (nonself) and to avoid making a response to those molecules that are self. This distinction, and the recognition of antigen, is conferred by specialized cells (lymphocytes) that bear on their surface antigen‐specific receptors.
Memory, a property shared with the nervous system, is the ability to recall previous contact with a foreign molecule and respond to it in a learned manner, that is, with a more rapid and larger response. Another term often used to describe immunological memory is anamnestic response.
When you reach the end of this book, you should understand the cellular and molecular bases of these features of the immune response.
Cells Involved in Adaptive Immune Responses
For many years, immunology remained an empirical subject in which the effects of injecting various substances into hosts were studied primarily in terms of the products elicited. Most progress came in the form of more quantitative methods for detecting these products of the immune response. A major change in emphasis came in the 1950s with the recognition that lymphocytes were the major cellular players in the immune response, and the field of cellular immunology came to life.
A convenient way to define the cell types involved in adaptive immunity is to divide the host defense mechanisms into two categories, namely B‐cell and T‐cell responses. While this is an oversimplified definition, it is, by and large, the functional outcome of adaptive immune responses. Thus, defining the cells involved begins with a short list, namely B and T cells. These cells are derived from a common lymphoid precursor cell but differentiate along different developmental lines, as discussed in detail in Chapters 8–10. In short, B cells develop and mature in the bone marrow whereas T‐cell precursors emerge from the bone marrow and undergo critical maturation steps in the thymus.
Antigen‐presenting cells, such as macrophages and dendritic cells, constitute the third cell type that participates in the adaptive immune response. Although these cells do not have antigen‐specific receptors as do the lymphocytes, they process and present antigen to the antigen‐specific receptors expressed by T cells. The APCs express a variety of cell‐surface molecules that facilitate their ability to interact with T cells. Among these are the major histocompatibility complex (MHC) molecules as discussed in Chapter 8. MHC molecules are encoded by a set of polymorphic genes expressed within a population. While we now understand that their physiological role is concerned with T cell–APC interactions, in clinical settings, MHC molecules determine the success or failure of organ and tissue transplantation. In fact, this observation facilitated their discovery and the current terminology (major histocompatibility complex) used to define these molecules. Physiologically, APCs process protein antigens intracellularly, resulting in the constellation of peptides that noncovalently bind to MHC molecules and ultimately get displayed on the cell surface.
Other cell types, such as neutrophils and mast cells, also participate in adaptive immune responses. In fact, they participate in both innate and adaptive immunity. While these cells have no specific antigen recognition properties and can be activated by a variety of substances, they are an integral part of the network of cells that participate in host defenses and often display potent immunoregulatory properties.
HUMORAL AND CELLULAR IMMUNITY
Adaptive immune responses have historically been divided into two separate arms of defense: B‐cell‐mediated or humoral immune responses, and T‐cell‐mediated or cellular responses. Today, while we recognize that B and T cells have very distinct yet complementary molecular and functional roles within our immune system, we understand that the two arms are fundamentally interconnected at many levels. “Experiments of nature,” a term coined by Robert A. Good in the 1950s when describing the immune status of humans with a congenital mutation associated with an athymic phenotype, have provided significant insights related to the interdependence of these two arms of the immune system. Athymic mice that fail to develop thymic tissue (a similar phenomenon in humans is called DiGeorge syndrome) results in a profound T‐cell deficiency with accompanying abnormalities in B‐cell function. The molecular explanation for the latter is now well understood. Without T‐cell help, B cells are unable to generate normal antibody responses and, in particular, to undergo immunoglobulin class switching (see Chapter 9). The help normally provided
