Human Physiology, 14th edition (2016)

522 Chapter 15

abnormal production of one group of antibodies (of the

IgM type) that attack other antibodies (of the IgG type).

This contributes to an inflammation reaction of the joints

characteristic of the disease.

4. Antibodies produced against foreign antigens may

cross-react with self-antigens. Autoimmune diseases of

this sort can occur, for example, as a result of Streptococ-

cus bacterial infections. Antibodies produced in response

to antigens in this bacterium may cross-react with self-

antigens in the heart and kidneys. The inflammation induced

by such autoantibodies can produce heart damage (includ-

ing the valve defects characteristic of rheumatic fever )

and damage to the glomerular capillaries in the kidneys

( glomerulonephritis ).

5. Self-antigens, such as receptor proteins, may be pre-

sented to the helper T lymphocytes together with class-2

MHC molecules. Normally, only antigen-presenting

cells (macrophages, dendritic cells, and antigen-activated

B cells) produce class-2 MHC molecules, which are asso-

ciated with foreign antigens and recognized by helper T

cells. Perhaps as a result of viral infection, however, cells

that do not normally produce class-2 MHC molecules may

start to do so and, in this way, present a self-antigen to the

helper T cells. In Graves’ disease, for example, the thyroid

cells produce class-2 MHC molecules, and the immune

system produces autoantibodies against the TSH receptor

proteins in the thyroid cells. These autoantibodies, called

TSAb ’s for “thyroid-stimulating antibody,” interact with

the TSH receptors and overstimulate the thyroid gland.

Similarly, in type 1 diabetes mellitus, the beta cells of the

pancreatic islets abnormally produce class-2 MHC mol-

ecules, resulting in autoimmune destruction of the insulin-

producing cells.

6. Autoimmune diseases may result when there is inade-

quate activity of regulatory (suppressor) T lymphocytes.

Regulatory T lymphocytes dampen the immune response,

and thus act to suppress autoimmune diseases and the

chronic inflammation associated with them. There is evi-

dence that other T lymphocytes can be converted into regu-

latory T lymphocytes by activation of a transcription factor

known as FOXP3. Thus, inadequate expression of this gene

may lead to insufficient activity of regulatory T lympho-

cytes and result in autoimmune disease. Indeed, geneti-

cally engineered mice without the gene, and people with a

mutated FOXP3, suffer from severe autoimmune disease.

Immune Complex Diseases

The term immune complexes refers to antigen-antibody com-

binations that are free rather than attached to bacterial or other

cells. The formation of such complexes activates comple-

ment proteins and promotes inflammation. This inflammation

is normally self-limiting because the immune complexes are

removed by phagocytic cells. When large numbers of immune

complexes are continuously formed, however, the inflam-

mation may be prolonged. Also, the dispersion of immune

thyroid follicles, for example, can stimulate the produc-
tion of autoantibodies and autoreactive T lymphocytes
that cause the destruction of the thyroid; this occurs in
Hashimoto’s thyroiditis. Similarly, autoantibodies devel-
oped against lens protein in a damaged eye may cause the
destruction of a healthy eye (in sympathetic ophthalmia ).
2. A self-antigen that is otherwise tolerated may be
altered by combining with a foreign hapten. The dis-
ease thrombocytopenia (low platelet count), for example,
can be caused by the autoimmune destruction of thrombo-
cytes (platelets). This occurs when drugs such as aspirin,
sulfonamide, antihistamines, digoxin, and others combine
with platelet proteins to produce new antigens. The symp-
toms of this disease usually disappear when the person
stops taking these drugs.
3. Antibodies may be produced that are directed against
other antibodies. Such interactions may be necessary for
the prevention of autoimmunity, but imbalances may actu-
ally cause autoimmune diseases. Rheumatoid arthritis, for
example, is an autoimmune disease associated with the

Disease Antigen

Postvaccinal and

postinfectious

encephalomyelitis

Myelin, cross-reactive

Aspermatogenesis Sperm

Sympathetic ophthalmia Uvea

Hashimoto’s disease Thyroglobulin

Graves’ disease Receptor proteins for TSH

Autoimmune hemolytic

disease

I, Rh, and others on surface of

RBCs

Thrombocytopenic

purpura

Hapten-platelet or hapten-

absorbed antigen complex

Myasthenia gravis Acetylcholine receptors

Rheumatic fever Streptococcal, cross-reactive

with heart valves

Glomerulonephritis Streptococcal, cross-reactive

with kidney

Rheumatoid arthritis IgG

Systemic lupus

erythematosus

DNA, nucleoprotein, RNA, etc.

Diabetes mellitus (type 1) Beta cells in pancreatic islets

Multiple sclerosis Components of myelin sheaths

Table 15.10 | Some examples of
Autoimmune Diseases

Source: Modified from James T. Barrett, Textbook of Immunology, 5th ed.
Copyright © 1988 Mosby-Yearbook. Reprinted by permission.