Human Physiology, 14th edition (2016)

The Immune System 517

ability of antigen-presenting cells to activate B and T lympho-

cyte responses. For example, when adjuvants stimulate den-

dritic cell secretion of IL-2 and IL-12, they enhance the B cell

secretion of antibodies; when adjuvants stimulate dendritic

cell release of IL-4, IL-5, and IL-6, they stimulate the T cell–

mediated response. Scientists continue to develop new adjuvants

to bolster vaccinations against malaria, influenza, and cancer.

These adjuvant benefits occur because dendritic cells,

critically important in the adaptive immune response, contain

pattern-recognition receptors that bind to pathogen-associated

molecular patterns (PAMPs) and damage-associated molecu-

lar patterns (DAMPs)—a process previously described as part

of the innate immune response (section 15.1). These reactions

help determine the nature and effectiveness of the adaptive

immune response and thus the effectiveness of a vaccination.

Because the innate and adaptive immune responses function

together in this and other ways, the distinction between them is

less clear than was previously thought.

microorganisms that are antigenically similar but less patho-
genic (such as Jenner’s cowpox inoculations). The name for
these procedures— vaccinations (after the Latin word vacca,
meaning “cow”)—reflects the history of this technique. All of
these procedures cause the development of lymphocyte clones
that can combat the virulent pathogens by producing secondary
responses.
The first successful polio vaccine (the Salk vaccine) was
composed of viruses that had been inactivated by treatment
with formaldehyde. These “killed” viruses were injected into
the body, in contrast to the currently used oral (Sabin) vaccine.
The oral vaccine contains “living” viruses that have attenu-
ated virulence. These viruses invade the epithelial lining of
the intestine and multiply, but do not invade nerve tissue. The
immune system can, therefore, become sensitized to polio anti-
gens and produce a secondary response if polio viruses that
attack the nervous system are later encountered.
In summary, there are three ways that vaccines are cur-
rently produced. Vaccines may use:

1. “live” viruses with attenuated virulence that do not cause
   disease, but provoke strong immune responses against the
   virulent viruses. Examples include the Sabin polio vaccine
   and vaccinations against measles and mumps.


2. “killed” virulent viruses that do not cause the disease.
   Examples include the Salk polio vaccine.


3. recombinant viral proteins, produced through genetic
   engineering and given by themselves. Examples of this are
   the hepatitis B vaccine and attempted HIV vaccines.
   Immunizations improved after the 1920s with the dis-
   covery that certain molecules, called adjuvants, could boost
   the immune response when delivered together with the vac-
   cine antigens. Adjuvants are generally molecules associated
   with microbes, and it was later discovered that they are among
   the PAMPs (pathogen-associated molecular patterns) dis-
   cussed earlier as activating the innate immune system. Adju-
   vants enhance the adaptive immune response by boosting the

Process Results

Lymphocytes inherit

the ability to produce

specific antibodies.

Prior to antigen exposure, lymphocytes

that can make the appropriate

antibodies are already present in the

body.

Antigens interact with

antibody receptors

on the lymphocyte

surface.

Antigen-antibody interaction stimulates

cell division and the development

of lymphocyte clones that contain

memory cells and plasma cells that

secrete antibodies.

Subsequent exposure to

the specific antigens

produces a more

efficient response.

Exposure of lymphocyte clones to

specific antigens results in greater

and more rapid production of specific

antibodies.

Table 15.8 | Summary of the Clonal
Selection Theory (As Applied to B Cells)

Clinical Investigation CLUES

Timmy got a booster shot that contained inactivated tox-

ins from bacteria. He later cut himself on an old can.

• How does a vaccination offer protection against
  disease?


• What disease did Timmy’s booster shot protect him
  from when he cut himself?

Immunological Tolerance

The ability to produce antibodies against non-self (foreign)

antigens, while tolerating (not producing antibodies against)

self-antigens occurs during the first month or so of postnatal

life, when immunological competence is established. If a fetal

mouse of one strain receives transplanted antigens from a dif-

ferent strain, therefore, it will not recognize tissue transplanted

later in life from the other strain as foreign; consequently, it

will not immunologically reject the transplant.

The ability of an individual’s immune system to recog-

nize and tolerate self-antigens requires continuous exposure of

the immune system to those antigens. If this exposure begins

when the immune system is weak—as in fetal and early post-

natal life—tolerance is more complete and long lasting than

that produced by exposure beginning later in life. Some self-

antigens, however, are normally hidden from the blood, such

as thyroglobulin within the thyroid gland and lens protein in

the eye. An exposure to these self-antigens results in antibody

production just as if these proteins were foreign. Antibodies

made against self-antigens are called autoantibodies. Killer

T cells that attack self-antigens are called autoreactive T cells.

The mechanisms of immunological tolerance include

(1) clonal deletion, in which lymphocytes that recognize