518 Chapter 15
(serum containing antibodies), also called antitoxin, from an
animal that has been previously exposed to the pathogen. The
animal develops the lymphocyte clones and active immunity,
and thus has a high concentration of antibodies in its blood.
Since the person who is injected with these antibodies does not
develop active immunity, he or she must again be injected with
antitoxin upon subsequent exposures.
Intravenous immunoglobulin from the pooled plasma
samples of thousands of people is another medical application
of passive immunity. Pooling of plasma from so many differ-
ent people provides great IgG antibody diversity, and was first
used to help combat microbial infections in patients who have
primary immunodeficiency diseases. Intravenous immunoglob-
ulin is now used mostly to treat patients with autoimmune con-
ditions and cancer patients with compromised immune systems.
In a variation on the theme of passive immunity, animals
(such as mice, rabbits, or sheep) are injected with an antigen and
used to obtain monoclonal antibodies, which are produced by an
isolated, pure clone of cells. This clone is obtained by first extract-
ing from the animal a single B lymphocyte that produces antibod-
ies against the desired specific antigenic-determinant site. The B
lymphocyte is then fused in vitro with a cancerous myeloma cell;
this is done to form a hybrid cell that is able to divide indefinitely.
The cell divisions produce a clone called a hybridoma that
secretes anti bodies specific for a single antigenic-determinant
site. This has enabled monoclonal antibodies to be produced on a
commercial scale for diagnosis (of pregnancy, for example) and
other laboratory tests, as well as for medical treatments. There are
currently more than 25 approved therapeutic monoclonal anti-
bodies that target cytokines (such as tumor necrosis factor), IgE,
and other regulatory molecules for the treatment of many autoim-
mune diseases (section 15.6; see table 15.10 ), persistent allergic
asthma, and cancers. Examples of monoclonal antibodies used in
cancer treatments include trastuzumab (Herceptin), which targets
the HER2 receptor produced by 30% of invasive breast cancers;
and bevacizumab (Avastin), which blocks the binding of vascular
endothelial growth factor (VEGF) to its receptors for the treat-
ment of types of colorectal, lung, kidney, and brain cancers.
Active and passive immunity are compared in table 15.9.self-antigens are destroyed, and (2) clonal anergy (meaning “with-
out working”), in which lymphocytes that recognize self-antigens
are prevented from becoming activated. Central tolerance mech-
anisms are those that occur in the thymus (for T cells) and bone
marrow (for B cells). Central tolerance in the thymus is achieved
by the apoptosis and removal of auto-reactive T cells, whereas
central tolerance of B cells in the bone marrow may involve both
clonal deletion and anergy. Peripheral tolerance, involving lym-
phocytes outside of the thymus and bone marrow, is due to com-
plex mechanisms that produce anergy.
Peripheral tolerance mechanisms are needed because
as lymphocytes divide, they randomly generate new antigen
receptors due to gene rearrangements and somatic mutations
(described previously). This is beneficial because it allows the
immune system to respond to a wide variety of foreign anti-
gens, but it also creates lymphocytes throughout life that have
receptors for self-antigens. These lymphocytes would produce
autoimmune diseases without mechanisms to suppress their
activation. Scientists currently believe that this suppression is
provided partly by regulatory T lymphocytes ( T (^) reg ). In a dem-
onstration of this process, removal of the thymus from mice
between two and four days old resulted in autoimmune dis-
ease, which was reversed by adding back T reg cells.
Passive Immunity
The term passive immunity refers to the immune protection
that can be produced by the transfer of antibodies to a recipient
from a human or animal donor. The donor has been actively
immunized, as explained by the clonal selection theory. The
person who receives these ready-made antibodies is thus pas-
sively immunized to the same antigens. Passive immunity also
occurs naturally in the transfer of immunity from mother to
fetus during pregnancy and from mother to baby during nursing.
The ability to mount a specific immune response—called
immunological competence —does not develop until about a
month after birth. The fetus, therefore, cannot immunologically
reject its mother. The immune system of the mother is fully com-
petent but does not usually respond to fetal antigens for reasons
that are not completely understood. Some IgG antibodies from
the mother do cross the placenta and enter the fetal circulation,
however, and these serve to confer passive immunity to the fetus.
The fetus and the newborn baby are thus immune to the
same antigens as the mother. However, because the baby did
not itself produce the lymphocyte clones needed to form these
antibodies, such passive immunity gradually disappears. If the
baby is breast-fed, it can receive additional antibodies of the
IgA subclass in its mother’s milk and colostrum (the secretion
an infant feeds on for the first two or three days until the onset
of true lactation). This provides additional passive immunity
until the baby can produce its own antibodies through active
immunity (see chapter 20, fig. 20.54).
Passive immunizations are used clinically to protect peo-
ple who have been exposed to extremely virulent infections
or toxins, such as tetanus, hepatitis, rabies, and snake venom.
In these cases, the affected person is injected with antiserum
| CHECKPOINT
8a. Describe three methods used to induce active immunity.
8b. Using graphs to illustrate your discussion, explain the
characteristics of the primary and secondary immune
responses.
8c. Explain the clonal selection theory and indicate how
this theory accounts for the secondary response.
8d. Define immunological tolerance, and explain
mechanisms that may be responsible for T and B
lymphocytes’ tolerance to self-antigens.- Describe passive immunity and give examples
of how it may occur naturally and how it may be
conferred by artificial means.