Human Physiology, 14th edition (2016)

The Immune System 521

15.6 DISEASES CAUSED BY THE

IMMUNE SYSTEM

Immune mechanisms that normally protect the body are

very complex and subject to errors that can result in dis-

eases. Autoimmune diseases and allergies are two catego-

ries of disease that are caused not by an invading pathogen

but instead by a derangement in the normal functions of

the immune system.

Interestingly, recent research has shown that NK cells,
like the cells of the adaptive immune system, can produce
long lasting “memory” cells and mount a stronger secondary
response to a subsequent challenge. Thus, although NK cells
are considered part of the innate immune system, they can
have characteristics of the adaptive immune response. The dis-
covery of a type of T cell scientists have dubbed natural killer
T cells ( NKT cells ), which respond to lipid antigens and have
both innate and adaptive immune characteristics, also blurs
the distinction between these divisions of the immune system.

Effects of Aging and Stress

Susceptibility to cancer varies greatly. The Epstein-Barr virus
that causes Burkitt’s lymphoma in some individuals (mainly in
Africa), for example, can also be found in healthy people through-
out the world. Most often the virus is harmless; in some cases, it
causes mononucleosis (involving a limited proliferation of white
blood cells). Only rarely does this virus cause the uncontrolled
proliferation of leukocytes characteristic of Burkitt’s lymphoma.
The reasons for these differences in response to the Epstein-Barr
virus, and indeed for the differing susceptibilities of people to
other forms of cancer, are not well understood.
It is known that cancer risk increases with age. Accord-
ing to one theory, this is because aging lymphocytes gradually
accumulate genetic errors that decrease their effectiveness. The
functions of the thymus also decline with age in parallel with a
decrease in cell-mediated immune competence. Both of these
changes, and perhaps others not yet discovered, could increase
susceptibility to cancer.
Numerous experiments have demonstrated that tumors
grow faster in experimental animals subjected to stress than
they do in unstressed control animals. This is attributed to
the stress-induced increase in corticosteroid secretion (chap-
ter 11), which suppresses the immune system; indeed, the
immunosuppressive effects of cortisone are used medically for
treating chronic inflammatory diseases and for reducing the
immune rejection of transplanted organs. Some recent experi-
ments, however, suggest that the stress-induced suppression of
the immune system may also be due to other factors that do not
involve the adrenal cortex. Future advances in cancer therapy
may incorporate methods of strengthening the immune system
into protocols aimed at directly destroying tumors.

| CHECKPOINT

10a. Explain why cancer cells are believed to be

dedifferentiated, and describe some of the clinical

applications of this concept.

10b. Define the term immunological surveillance, and

identify the cells involved in this function.

10c. Explain the possible relationship between stress and

susceptibility to cancer.

LEARNING OUTCOMES

After studying this section, you should be able to:

11. Explain the nature of autoimmune diseases.


12. Explain immediate and delayed hypersensitivity.

The ability of the normal immune system to tolerate self-antigens

while it identifies and attacks foreign antigens provides a specific

defense against invading pathogens. In every individual, how-

ever, this system of defense against invaders at times commits

domestic offenses. This can result in diseases that range in sever-

ity from the sniffles to sudden death.

Diseases caused by the immune system can be grouped into

three interrelated categories: (1) autoimmune diseases, (2) immune

complex diseases, and (3) allergy, or hypersensitivity. It is impor-

tant to remember that these diseases are not caused by foreign

pathogens but by abnormal responses of the immune system.

Autoimmunity

Autoimmune diseases are those produced by failure of the

immune system to recognize and tolerate self-antigens. This

failure results in the activation of autoreactive T cells and the

production of autoantibodies by B cells, causing inflammation

and organ damage ( table 15.10 ). Cell division of B lymphocytes

within germinal centers of lymph nodes increases antibody

diversity through somatic hypermutation and immunoglobulin

class switching (discussed in section 15.2). The production of

autoreactive B cells (those that produce autoantibodies) occurs

as an inevitable byproduct of these necessary processes. Auto-

immune diseases result when those cells become exposed to

and stimulated by the appropriate self-antigen.

There are over 40 known or suspected autoimmune dis-

eases that affect 5% to 7% of the population. Two-thirds of

those affected are women. The most common autoimmune dis-

eases are rheumatoid arthritis, type 1 diabetes mellitus, multiple

sclerosis, Graves’ disease, glomerulonephritis, thyroiditis, per-

nicious anemia, psoriasis, and systemic lupus erythematosus.

There are at least six reasons why self-tolerance may fail:

1. An antigen that does not normally circulate in the

blood may become exposed to the immune system.

Thyroglobulin protein that is normally trapped within the