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U N I T 4
Infection and Immunity
host that can stimulate an immune response. These for-
eign molecules are recognized by receptors on immune
cells and by secreted proteins, called
antibodies
or
immu-
noglobulins,
made in response to the antigen. Antigens
include bacteria, fungi, viruses, protozoa, and parasites.
Nonmicrobial agents such as plant pollens, poison ivy
resin, insect venom, and transplanted organs can also
act as antigens. Although most antigens are macromol-
ecules, such as proteins and polysaccharides, lipids and
nucleic acids occasionally serve as antigens.
Antigens, which in general are large and chemically
complex, are biologically degraded into smaller chemical
units or peptides. These discrete, immunologically active
sites on antigens are called
antigenic determinants,
or
epitopes
. It is the unique molecular shape of the epitope
that is recognized by a specific immunoglobulin receptor
found on the surface of a lymphocyte or by an antigen-
binding site of a secreted antibody (Fig. 15-5). A single
antigen may contain multiple antigenic determinants,
each stimulating a distinct clone of T and B lympho-
cytes. For example, different proteins that comprise the
influenza virus may function as unique antigens (A, B, C,
H, and N antigens), each of which contains several anti-
genic determinants. Hundreds of antigenic determinants
are found on structures such as the bacterial cell wall.
Smaller substances (molecular masses <10,000 dal-
tons) usually are unable to stimulate an adequate immune
response by themselves. When these low–molecular-
weight compounds, known as
haptens,
combine with
larger carrier molecules, they function as antigens. The
hapten–carrier complex can stimulate the production
of antibodies, some of which combine with the hapten
portion of the complex. An allergic response to the anti-
biotic penicillin is an example of a medically important
reaction due to hapten–carrier complexes. Penicillin
(molecular mass of approximately 350 daltons) is
normally a nonantigenic molecule. However, in some
individuals, it can chemically combine with body pro-
teins to form larger complexes that can then generate a
potentially harmful immune allergic response.
Cells and Molecules of Adaptive
Immunity
B and T lymphocytes are the effector cells of the adap-
tive immune system that specifically recognize and
respond to foreign antigens. Accessory cells, such as
macrophages and dendritic cells, function as antigen-
presenting cells by first processing a complex antigen
into epitopes and then displaying the foreign and self-
peptides on their membranes so that appropriate acti-
vation of lymphocytes occurs. We will begin with a
discussion of the antigen-presenting cells, move to the
lymphocytes, and end with the MHC molecules that dis-
play antigens for recognition by T lymphocytes.
Antigen-Presenting Cells
Macrophages are key members of the mononuclear
phagocytic system that engulf and digest microbes and
other foreign substances. The monocytes migrate from
the blood to various tissues, where they mature into the
major tissue phagocytes, the macrophages. As the gen-
eral scavenger cells of the body, the macrophages can
be fixed in a tissue or free to migrate from an organ
to lymphoid tissues. The tissue macrophages are scat-
tered in connective tissue or may be clustered in the lung
(alveolar macrophages), liver (Kupffer cells), spleen,
lymph nodes, peritoneum, or central nervous system
(microglial cells).
Dendritic cells are found in most tissues where anti-
gen enters the body and in the peripheral lymphoid tis-
sues, where they function as potent antigen-presenting
cells. In these environments, dendritic cells can acquire
specialized functions and appearances, as do macro-
phages. Langerhans cells are specialized dendritic cells
in the skin, whereas follicular dendritic cells are found
in the lymph nodes. Langerhans cells are constantly sur-
veying the skin for antigen and can transport foreign
material to a nearby lymph node. Skin dendritic cells
and macrophages also are involved in cell-mediated
immune reactions of the skin such as allergic contact
dermatitis.
Lymphocytes
Like other blood cells, B and T lymphocytes are generated
from stem cells in the bone marrow. Undifferentiated,
immature lymphocytes move to the central lymphoid
tissues, where they develop into distinct types of mature
lymphocytes (Fig. 15-6). B lymphocytes mature in the
bone marrow and then move to the peripheral lymphoid
tissues where they are exposed to antigen and stimulated
to differentiate into antibody-producing plasma cells.
T lymphocytes complete their maturation in the thy-
mus and then move to the peripheral lymphoid tissues,
where they function to produce cell-mediated immunity,
Epitopes
(antigenic
determinants)
Antibody
A
Antibody
C
Antibody
B
Antigen-
binding
sites
Antigen
FIGURE 15-5.
Multiple epitopes on a complex antigen being
recognized by their respective (A, B, C) antibodies.