Human Physiology, 14th edition (2016)

The Immune System 523

complexes to other sites can lead to widespread inflammation
and organ damage. The damage produced by this inflamma-
tory response is called immune complex disease.
Immune complex diseases can result from infections by
bacteria, parasites, and viruses. In hepatitis B, for example, an
immune complex that consists of viral antigens and antibodies
can cause widespread inflammation of arteries ( periarteritis ).
Arterial damage is caused not by the hepatitis virus itself but
by the inflammatory process.
Immune complex disease can also result from the forma-
tion of complexes between self-antigens and autoantibodies.
This produces systemic autoimmune disease, where the inflam-
mation and tissue damage is not limited to a particular location.
In rheumatoid arthritis, there is inflammation of the
synovial membranes and fluid of peripheral joints that causes
damage to the articular cartilage and bone of the joints.
Although the initial cause of this disease is unknown, there
appears to be an early infiltration of the synovial membranes
by helper T cells. These secrete pro-inflammatory cytokines
that lead to the activation of B cells, which secrete autoanti-
bodies. The antibodies, including rheumatoid factors —IgM
antibodies that bind to the F c portion of IgG antibodies, creat-
ing immune complexes—activate complement proteins. These
extend the inflammation, attracting and activating phagocytic
polymorphonuclear leukocytes. Rheumatoid arthritis affects
joints symmetrically on both sides of the body and can have
systemic symptoms (fatigue, anorexia, and weakness) owing to
the release of tumor necrosis factor, IL-1, IL-6, and other pro-
inflammatory cytokines into the circulation.
Systemic lupus erythematosus (SLE) is a systemic auto-
immune disease involving the kidneys, joints, skin, central ner-
vous system, and other body structures. In SLE, the affected
people (90% of whom are women in their childbearing years)
produce a wide range of autoantibodies. However, what most
distinguishes SLE is the production of IgG antibodies against
their own nuclear constituents; indeed, laboratory tests for
antinuclear antibodies (ANA) are used to help diagnose the
disease. People with SLE produce autoantibodies against their
own chromatin (DNA and proteins), small nuclear ribonucleo-
protein (snRNP), and others. Cells undergoing apoptosis or
necrosis release these nuclear constituents, and so the immune
system is always exposed to these antigens. For reasons not
presently understood, people with SLE lose immune tolerance
to these self-antigens. The binding of the nuclear antigens to
autoantibodies can form immune complexes throughout the
body, provoking inflammation that can damage organs.
For example, immune complexes may enter the glomeru-
lar capillaries of the kidneys (the filtering units; chapter 17,
section 17.2), provoking inflammation that can produce glomerulo-
nephritis. Multiple genes may confer a genetic susceptibility to
SLE, but interaction with the environment is also important. For
example, exposure to ultraviolet light (in sunlight), or a variety of
infections, may trigger SLE. Patients with SLE are treated with
antimalarial drugs (that inhibit the toll-like receptors, which pro-
mote autoimmunity) and various anti-inflammatory and immuno-
suppressive drugs.

Allergy

The term allergy, often used interchangeably with hypersensi-

tivity, refers to particular types of abnormal immune responses

to antigens, which are called allergens in these cases. There

are two major forms of allergy: (1) immediate hypersensitiv-

ity, which is due to an abnormal B lymphocyte response to an

allergen that produces symptoms within seconds or minutes,

and (2) delayed hypersensitivity, which is an abnormal T cell

response that produces symptoms between 24 and 72 hours

after exposure to an allergen. These two types of hypersensitiv-

ity are compared in table 15.11.

Immediate Hypersensitivity

Immediate hypersensitivity can produce allergic rhini-

tis (chronic runny or stuffy nose); conjunctivitis (red eyes);

allergic asthma; atopic dermatitis (urticaria, or hives); and

food allergies. These symptoms result from the immune

response to the allergen. In people who are not allergic, the

allergen stimulates one type of helper T lymphocyte, the T H 1

cells, to secrete interferon- g and interleukin-2. In people

who are allergic, dendritic cells stimulate the other type of

helper T lymphocytes, the T H 2 cells, to secrete other lym-

phokines, including interleukin-4 and interleukin-13. These

recruit eosinophils, promote mucus production from goblet

cells, and stimulate smooth muscles in the bronchioles to pro-

mote the airway hyper responsiveness of asthma (chapter 16,

section 16.3). These lymphokines also stimulate the B lym-

phocytes and plasma cells to secrete antibodies of the IgE

subclass instead of the normal IgG antibodies. IgE antibodies

protect against wormlike helminth parasites (often ingested

in undercooked meats), but also mediate allergic immediate

hypersensitivity reactions.

Characteristic

Immediate

Reaction

Delayed

Reaction

Time for onset of

symptoms

Within several

minutes

Within 1 to 3 days

Lymphocytes

involved

B cells T cells

Immune effector IgE antibodies Cell-mediated immunity

Allergies most

commonly

produced

Hay fever, asthma,

and most

other allergic

conditions

Contact dermatitis

(such as to poison

ivy and poison oak)

Therapy Antihistamines and

adrenergic drugs

Corticosteroids

(such as cortisone)

Table 15.11 | Allergy: Comparison of

Immediate and Delayed Hypersensitivity

Reactions