s e c t io n
35.5
Molecules and Chemical Processes of the Immune System
811
agent antibodies synthesized, and the infectious agents
destroyed. Because the selection of B cells and T cells
by an antigen results in proliferation of only clones that
recognize a specific epitopes of the antigen, an amplified,
specific response occurs. Persistence of some of the spe-
cific B and T lymphocytes provides memory of the first
encounter with the infectious organism so that subsequent
infections by the same agent are opposed by a faster and
more effective immune response.
35.3 Antibody-Dependent Cell-Mediated
Cytotoxicity
Another process involving antigen-antibody complexes
exists for killing infected cells. In this process, circulat-
ing antibodies bind to epitopes of the viral proteins or
glycoproteins exposed on the host cell membrane sur-
face. These “antibody-tagged” cells are then recognized
by granular lymphocytes called natural killer (NK) cells.
Recognition of the “tagged,” infected cells by NK cells
occurs through a structurally similar region of all anti-
body molecules (the Fc region), not through the specific
antigen-recognizing regions of the antibody. This mech-
anism is called antibody-dependent, cell-mediated cyto-
toxicity (ADCC). Immune response involving neutrophils
and NK cells is schematically illustrated in Figure 35-4.
(Interaction of a bacterial protein with the Fc region of an
antibody is shown in Figure 35-10).
NK cells, monocytes, neutrophils, and macrophages are
involved in IgG-mediated ADCC (see below); eosinophils
are involved in IgE-mediated ADCC.
FIGURE 35-4
(Also see color figure.) Microbe destruction by neutrophils and
antibody-dependent, cell-mediated cytotoxicity. (A) Neutrophils recognize
and attack antibody-tagged microorganisms by a mechanism called
antibody-dependent, cell-mediated cytotoxicity (ADCC). In this defense
mechanism, microbes “tagged” by antibodies are destroyed by a
respiratory burst of Oj , H
2
O
2
, and NO produced by the attacking
neutrophils. (B) In a similar way, natural killer (NK) cells recognize
antibody-tagged virus-infected cells and tumor cells.
35.4 Distinguishing Self from Nonself
Distinguishing self from nonself is critical to homeostatic
immune system function. If self is “perceived” as foreign,
autoimmunity and autoimmune disease are the conse-
quence. The ability to recognize self constitutes one form
of immune tolerance. Conversely, if pathogenic organisms
or toxic substances are unrecognized or unopposed, the
consequential infection and organ damage is debilitating
and frequently fatal.
Tolerance
or unresponsiveness
to
self-antigens
is
actively achieved. Exclusion of T cells that recognize
epitopes on molecules that are “self” occurs in the thy-
mus during T-cell differentiation and proliferation. Self-
reactive T cells are “instructed” to die, a process generally
described as negative selection. B cells that recognize epi-
topes on molecules that are “self” are distinguished from B
cells that recognize foreign antigens by a mechanism gen-
erally described as positive selection. Positive selection
occurs in lymphoid tissues. In this process, B cells stim-
ulated by T-helper cells proliferate. B cells that are not
stimulated to produce antibodies or are precluded from
responding by the actions of T-suppressor cells die by
apoptosis.
Apoptosis,
programmed cell death, occurs by mecha-
nisms that include proteolytic processes catalyzed by cas-
pases (a group of enzymes that are responsible for the de-
struction of intracellular proteins). Failed apoptosis can be
a cause of autoimmunity. Autoimmune diabetes mellitus,
caused by destruction of
/3
cells in islets of Langerhans in
the pancreas, is an example of failed apoptosis. Similarly,
chronic
lymphocytic leukemia
is an expression of B cells
surviving beyond their normal, apoptosis-determined life-
times.
B-cell lymphomas
are cancerous growths that are
caused by delayed apoptosis, not by stimulation of cell
division. One approach to the development of therapeu-
tic drugs for leukemia includes designing molecules that
regulate apoptosis.
Autoimmune disease can also arise from a foreign sub-
stance possessing an epitope very similar to an epitope
that is found on a host molecule. This situation, termed
“molecular mimicry,” is the cause of post-streptococcal
rheumatic fever because an epitope on the streptococcal
M protein elicits formation antibody that reacts with an
epitope on myosin.
35.5 Molecules and Chemical Processes of the
Immune System
The highly coordinated and regulated responses of the
cells of the immune system directly reflect properties of
