Inflammation and adaptive immunity differ in several key ways.

First, adaptive immunity develops more slowly than inflammation.

The components of inflammation preexist in the blood and tissues and
are activated immediately after and as a result of tissue damage.
Adaptive immunity is inducible. The effectors of the immune response,
lymphocytes and antibodies, do not preexist but must be produced in
response to infection. Second, each inflammatory response is similar
(although not identical) regardless of differences in the cause of tissue
damage or whether the inflammatory site is sterile or contaminated
with microorganisms. The adaptive immune response is exquisitely
specific. The lymphocytes and antibodies induced in response to a
particular infectious agent are extremely specific to that agent. A
different infectious agent will induce a different battery of
lymphocytes and antibodies. Third, the residual mediators of
inflammation must be removed quickly to limit damage to
surrounding healthy tissue and allow healing. The effectors of the
adaptive immune response are long-lived and systemic, providing
long-term protection against a specific infectious agent. Fourth,
activation of the inflammatory response to recurrent tissue damage or
repeated infection with the same microorganism is generally identical.
The adaptive immune response has memory. If reinfected with the
same microorganism, protective lymphocytes and antibody are
produced rapidly, thus providing permanent long-term protection.
Thus the adaptive immune response is distinguished by being
inducible, specific, and long-lived, and by having memory.
The collaborative and beneficial nature of inflammation and
adaptive immunity can, on occasion, fail. Chapter 9 discusses these
medically relevant aberrations in both inflammation and immunity,
including allergies, diseases that involve unwanted immunologic
destruction of healthy tissue, and diseases that are caused by a
deficiency in the normal immune or inflammatory responses. Chapter
10 presents an overview of infection and Chapter 11 discusses the
connection between stress and disease and the interrelatedness of the
immune, nervous, and endocrine systems.

General Characteristics of Adaptive

Immunity
The adaptive immune system has its own vocabulary (Fig. 8.2). The
immune system of the normal adult is continually challenged by a
spectrum of substances that it may recognize as foreign, or “nonself.”
These substances, called foreign antigens, are often associated with
pathogens such as viruses, bacteria, fungi, or parasites, although they
are also found on noninfectious environmental agents such as pollens,
foods, and bee venom, and still others are associated with clinically
derived drugs, vaccines, transfusions, and transplanted tissues (Table
8.1). The products (i.e., effectors) of the adaptive immune response
include antibodies (sometimes called immunoglobulins) and
lymphocytes that are specific for particular antigens.
 FIGURE 8.2 Overview of Immune Response. The immune response can be
separated into two phases: the generation of clonal diversity and clonal
selection. During the generation of clonal diversity, lymphoid stem cells
from the bone marrow migrate to the central lymphoid organs (the thymus
or regions of the bone marrow), where they undergo a series of cellular
division and differentiation stages resulting in either immunocompetent T
cells from the thymus or immunocompetent B cells from the bone marrow.
(This process is outlined in more detail in Figs. 8.9 and 8.12.) These cells
are still naïve in that they have never encountered foreign antigen. The
immunocompetent cells enter the circulation and migrate to the secondary
lymphoid organs (e.g., spleen and lymph nodes), where they take up
residence in B- and T-cell–rich areas. The clonal selection phase is initiated
by exposure to foreign antigen. The antigen is usually processed by
antigen-presenting cells (APCs) for presentation to helper T cells (Th cells)
(more detail in Fig. 8.16). The intercellular cooperation among APCs, Th
cells, and immunocompetent T and B cells results in a second stage of
cellular proliferation and differentiation (more details in Figs. 8.18 and
8.21). Because antigen has “selected” those T and B cells with compatible
antigen receptors, only a small population of T and B cells undergoes this
process at one time. The result is an active cellular immunity or humoral
immunity, or both. Cellular immunity is mediated by a population of
“effector” T cells that can kill targets (cytotoxic T cells) or regulate the
immune response (T-regulatory cells), as well as a population of memory
cells (memory T cells) that can respond more quickly to a second challenge
with the same antigen. Humoral immunity is mediated by a population of
soluble proteins (antibodies) produced by plasma cells and by a population
of memory B cells that can produce more antibody rapidly to a second
challenge with the same antigen.

TABLE 8.1
CLINICAL USE OF ANTIGEN OR ANTIBODY
PROTECTION:
ANTIGEN COMBAT ACTIVE PROTECTION: DIAGNOSIS THERAPY
SOURCE VACCINATION
DISEASE
Infectious agents Neutralize or destroy Induce safe and Measure Passive treatment
pathogenic protective circulating with antibody to
microorganisms immune antigen from treat or prevent
(e.g., antibody response (e.g., infectious infection (e.g.,
response against recommended agent or administration
viral infections) childhood antibody of antibody
vaccines) (e.g., against hepatitis
diagnosis of A)
hepatitis B
infection)

Cancers Prevent tumor growth Prevent cancer Measure Immunotherapy

or spread (e.g., growth or circulating (e.g., treatment
immune spread (e.g., antigen (e.g., of cancer with
surveillance to vaccination circulating antibodies
prevent early with cancer PSA for against cancer
cancers) antigens) diagnosis of antigens)
prostate
cancer)

Environmental Prevent entrance into No clear example Measure Immunotherapy

substances body (e.g., secretory circulating (e.g.,
IgA limits systemic antigen or administration
exposure to antibody of antigen for
potential allergens) (e.g., desensitization
diagnosis of of individuals
allergy by with severe
measuring allergies)
circulating
IgE)

Self-antigens Immune system Some cases of Measure No clear example

tolerance to self- vaccination alter circulating
antigens, which may tolerance to self- antibody
be altered by an antigens leading against self-
infectious agent to autoimmune antigen for
leading to disease diagnosis of
autoimmune disease autoimmune
(see Chapter 9) disease (see
Chapter 9)

IgA, Immunoglobulin A; PSA, prostate-specific antigen.

Specificity and memory are primary characteristics that differentiate

the immune response from other protective mechanisms. This chapter
first discusses the nature of that specificity by defining the various
types of antigens recognized by the immune system, the ways in
which they are recognized by antibodies and lymphocytes, and the
specific intercellular recognition molecules that are necessary for
effective immune responses. After the recognition molecules are
defined, the development of the immune response is discussed. An
immune response can be divided into two phases (see Fig. 8.2). In the
fetus, well before being exposed to any infectious microorganisms,
lymphocytes undergo extensive differentiation and proliferation.
These events occur in the primary lymphoid organs (thymus and bone
marrow). Some lymphoid stem cells in humans enter the thymus and
differentiate into T lymphocytes (T cells, T indicating thymus
derived) and others enter specific regions in the bone marrow and
differentiate into B lymphocytes (B cells, B indicating bone marrow
derived). Each type of cell develops origin-specific cell surface
proteins that identify them as T or B cells. Both B and T cells also
develop cell surface antigen receptors. The receptors are remarkable
because an individual B or T cell is programmed to recognize only one
specific antigen before having encountered that antigen. It is
estimated that each person has produced a population of B and T cells
with an extensive diversity of antigen receptors capable of recognizing
at least 108 different antigens. This process is called generation of
clonal diversity (see Fig. 8.2).
Lymphocytes leave the primary lymphoid organs as
immunocompetent but naïve B and T cells. They are
immunocompetent in that they have the capacity to respond to
antigen, but naïve in that they have not yet encountered antigen.
These cells enter the blood and lymphatic vessels and migrate to the
secondary lymphoid organs (e.g., lymph nodes, spleen) of the
systemic immune system (Fig. 8.3). Some take up residence in B-cell–
and T-cell–rich areas of those organs and others reenter the
circulation. Approximately 60% to 70% of circulating lymphocytes are
immunocompetent T cells, and 10% to 20% are immunocompetent B
cells.
 FIGURE 8.3 Lymphoid Tissues: Sites of B-Cell and T-Cell Differentiation.
Immature lymphocytes migrate through central (primary) lymphoid tissues:
the bone marrow (central lymphoid tissue for B lymphocytes) and the
thymus (central lymphoid tissue for T lymphocytes). Mature lymphocytes
later reside in the T- and B-lymphocyte–rich areas of the peripheral
(secondary) lymphoid tissues.

The second phase, called clonal selection, is initiated by exposure

to foreign antigen usually related to infection (see Fig. 8.2). Antigen
reacts with, or selects, clones of B and T cells with surface receptors
against that specific antigen and initiates a process of further
differentiation and proliferation into mature effector cells. The process
requires the cooperation among a variety of cells in the secondary
lymphoid organs; most antigens need to be processed (antigen
processing) by phagocytic cells, primarily dendritic cells, that also
present the processed antigen on their surfaces and present (antigen
presentation) the antigen to lymphocytes. These cells are generally
called antigen-processing or antigen-presenting cells (APCs). Thus
begins a symphony of cellular interactions that define clonal
selection, involving APCs and several subsets of B and T cells,
intercellular adhesion through antigen receptors and specific
intercellular adhesion molecules, the production and response to
multiple cytokines, and eventual differentiation of
immunocompetent B and T cells into highly specialized effector
cells. B cells develop into plasma cells that become factories for the
production of antibody. T cells develop into several subsets that
identify and kill a target cell (T-cytotoxic cell [Tc cell]), regulate
the immune response by helping the clonal selection process (T-
helper cell [Th cell]), or suppress or limit the immune response
(T-regulatory cell [Treg cell]). Both B and T cells also
differentiate into very long-lived memory cells that exist for
decades or, in some cases, the life of the individual. Memory cells
“remember” the initial antigen and are rapidly activated if a
second exposure occurs to the same microorganism.