What Are Autoimmune Diseases?
The word "auto" is the Greek word for self. The immune system is a
complicated network of cells and cell components (called molecules) that
normally work to defend the body and eliminate infections caused by
bacteria, viruses, and other invading microbes. If a person has an
autoimmune disease, the immune system mistakenly attacks self, targeting
the cells, tissues, and organs of a person's own body. A collection of
immune system cells and molecules at a target site is broadly referred to
as inflammation.
There are many different autoimmune diseases, and
they can each affect the body in different ways. For example, the
autoimmune reaction is directed against the brain in multiple sclerosis
and the gut in Crohn's disease. In other autoimmune diseases such as
systemic lupus erythematosus (lupus), affected tissues and organs may vary
among individuals with the same disease. One person with lupus may have
affected skin and joints whereas another may have affected skin, kidney,
and lungs. Ultimately, damage to certain tissues by the immune system may
be permanent, as with destruction of insulin-producing cells of the
pancreas in Type 1 diabetes mellitus. |
Who Is Affected by Autoimmune Diseases?
Many of the autoimmune diseases are rare. As a group, however,
autoimmune diseases afflict millions of Americans. Most autoimmune
diseases strike women more often than men; in particular, they affect
women of working age and during their childbearing years.
Some
autoimmune diseases occur more frequently in certain minority populations.
For example, lupus is more common in African-American and Hispanic women
than in Caucasian women of European ancestry. Rheumatoid arthritis and
scleroderma affect a higher percentage of residents in some Native
American communities than in the general U.S. population. Thus, the
social, economic, and health impact from autoimmune diseases is
far-reaching and extends not only to family but also to employers,
co-workers, and friends. |
What Are the Causes of Autoimmune Diseases?
Are they contagious? No autoimmune disease has ever been shown
to be contagious or "catching." Autoimmune diseases do not spread to other
people like infections. They are not related to AIDS, nor are they a type
of cancer.
Are they inherited? The genes people inherit
contribute to their susceptibility for developing an autoimmune disease.
Certain diseases such as psoriasis can occur among several members of the
same family. This suggests that a specific gene or set of genes
predisposes a family member to psoriasis. In addition, individual family
members with autoimmune diseases may inherit and share a set of abnormal
genes, although they may develop different autoimmune diseases. For
example, one first cousin may have lupus, another may have
dermatomyositis, and one of their mothers may have rheumatoid
arthritis. |
Examples of Autoimmune Diseases:
(Listed by
the Main Target Organ)
|
| Nervous System: |
Gastrointestinal System: |
| |
Multiple sclerosis |
|
Crohn's Disease |
| |
Myasthenia gravis |
|
Ulcerative colitis |
| |
Autoimmune neuropathies |
|
Primary biliary cirrhosis |
| |
such as Guillain-Barré |
|
Autoimmune hepatitis |
| |
Autoimmune uveitis |
|
|
| |
|
|
Endocrine Glands: |
| |
Blood: |
|
Type 1 or immune-mediated |
| |
Autoimmune hemolytic anemia |
|
diabetes mellitus |
| |
Pernicious anemia |
|
Grave's Disease |
| |
Autoimmune thrombocytopenia |
|
Hashimoto's thyroiditis |
| |
|
|
Autoimmune oophoritis and |
| |
Blood Vessels: |
|
orchitis |
| |
Temporal arteritis |
|
Autoimmune disease of the |
| |
Anti-phospholipid syndrome |
|
adrenal gland |
| |
Vasculitides such as |
|
|
| |
Wegener's granulomatosis |
|
Multiple Organs Including the |
| |
Behcet's disease |
|
Musculoskeletal System:* |
| |
|
|
Rheumatoid arthritis |
| |
Skin: |
|
Systemic lupus erythematosus |
| |
Psoriasis |
|
Scleroderma |
| |
Dermatitis herpetiformis |
|
Polymyositis, dermatomyositis |
| |
Pemphigus vulgaris |
|
Spondyloarthropathies such as |
| |
Vitiligo |
|
ankylosing spondylitis |
| |
|
|
Sjogren's syndrome |
*These diseases are also called
connective tissue (muscle, skeleton, tendons, fascia, etc.)
diseases. | |
|
| The development of an autoimmune disease may
be influenced by the genes a person inherits together with the way the
person's immune system responds to certain triggers or environmental
influences. |
What other factors may influence the development of
autoimmune diseases? Some autoimmune diseases are known to begin or
worsen with certain triggers such as viral infections. Sunlight not only
acts as a trigger for lupus but can worsen the course of the disease. It
is important to be aware of the factors that can be avoided to help
prevent or minimize the amount of damage from the autoimmune disease.
Other less understood influences affecting the immune system and the
course of autoimmune diseases include aging, chronic stress, hormones, and
pregnancy. |
How Does the Immune System Work?
The immune system defends the body from attack by invaders recognized
as foreign. It is an extraordinarily complex system that relies on an
elaborate and dynamic communications network that exists among the many
different kinds of immune system cells that patrol the body. At the heart
of the system is the ability to recognize and respond to substances called
antigens whether they are infectious agents or part of the body (self
antigens). |
| Cells and molecules of the immune system protect the
nose from attack by a virus. |
 |
T
cell (lymphocyte) with a T-cell receptor on its surface |
T and B Cells
Most immune system cells are white blood
cells, of which there are many types. Lymphocytes are one type of white
blood cell, and two major classes of lymphocytes are T cells B cells. T
cells are critical immune system cells that help to destroy infected cells
and coordinate the overall immune response. The T cell has a molecule on
its surface called the T-cell receptor. This receptor interacts with
molecules called MHC (major histocompatibility complex). MHC molecules are
on the surfaces of most other cells of the body and help T cells recognize
antigen fragments. B cells are best known for making antibodies. An
antibody binds to an antigen and marks the antigen for destruction by
other immune system cells. Other types of white blood cells include
macrophages and neutrophils |
Macrophages and Neutrophils
Macrophages and
neutrophils circulate in the blood and survey the body for foreign
substances. When they find foreign antigens, such as bacteria, they engulf
and destroy them. Macrophages and neutrophils destroy foreign antigens by
making toxic molecules such as reactive oxygen intermediate molecules. If
production of these toxic molecules continues unchecked, not only are the
foreign antigens destroyed, but tissues surrounding the macrophages and
neutrophils are also destroyed. For example, in individuals with the
autoimmune disease called Wegener's granulomatosis, overactive |
A
macrophage engulfing a bacterium and releasing packets of toxic molecules
(reactive oxygen intermediates) that break down and destroy the
bacterium. |
macrophages and neutrophils that invade blood vessels
produce many toxic molecules and contribute to damage of the blood
vessels. In rheumatoid arthritis, reactive oxygen intermediate molecules
and other toxic molecules are made by overproductive macrophages and
neutrophils invading the joints. The toxic molecules contribute to
inflammation, which is observed as warmth and swelling, and participate in
damage to the joint.
MHC and Co-Stimulatory Molecules
MHC
molecules are found on all cell surfaces and are an active part of the
body's defense team. For example, when a virus infects a cell, a MHC
molecule binds to a piece of a virus (antigen) and displays the antigen on
the cell's surface. Cells that have the capability of displaying antigen
with MHC are called antigen-presenting cells. Each MHC molecule that
displays an antigen is recognized by a matching or compatible T-cell
receptor. Thus, an antigen-presenting cell is able to communicate with a T
cell about what may be occurring inside the cell. |
Upper left: a virus attacking a nerve cell. Lower right: a T cell
with a T-cell receptor recognizing a piece of a virus (antigen) on the MHC
of the infected nerve cell. |
However, for the T cell to respond to a foreign antigen
on the MHC, another molecule on the antigen-presenting cell must send a
second signal to the T cell. A corresponding molecule on the surface of
the T cells recognizes the second signal. These two secondary molecules of
the antigen-presenting cell and the T cell are called co-stimulatory
molecules. There are several different sets of co-stimulatory molecules
that can participate in the interaction of antigen-presenting cell with a
T cell.
Once the MHC and the T-cell receptor interact, and the
co-stimulatory molecules interact, there are several possible paths that
the T cell may take. These include T cell activation, tolerance or T cell
death. The subsequent steps depend in part on which co-stimulatory
molecules interact and how well they interact. Because these interactions
are so critical to the response of the immune system, researchers are
intensively studying them to find new therapies that could control or stop
the immune system attack on self tissues and organs. |
An antigen-presenting cell (for example, a
macrophage) with a foreign antigen on its MHC is recognized by a T-cell
receptor. In addition, co-stimulatory molecules on the antigen-presenting
cell and the T cell interact. |
Cytokines and Chemokines
One way T cells can
respond after the interaction of the MHC and the T-cell receptor, and the
interaction of the co-stimulatory molecules, is to secrete cytokines and
chemokines. Cytokines are proteins that may cause surrounding immune
system cells to become activated, grow, or die. They also may influence
non-immune system tissues. For example, some cytokines may contribute to
the thickening of the skin that occurs in people with scleroderma. |
After
the antigen-presenting cell and T cell interact through the MHC, T-cell
receptor and co-stimumlatory and molecules, the T cell becomes activated,
sending cytokine signals to other cells. |
Chemokines are small cytokine molecules that attract
cells of the immune system. Overproduction of chemokines contributes to
the invasion and inflammation of the target organ, which occurs in
autoimmune diseases. For example, overproduction of chemokines in the
joints of people with rheumatoid arthritis may result in invasion of the
joint space by destructive immune system cells such as macrophages,
neutrophils, and T cells.
Antibodies
B cells are another
critical type of immune system cell. They participate in the removal of
foreign antigens from the body by using a surface molecule to bind the
antigen or by making specific antibodies that can search out and destroy
specific foreign antigens. However, the B cell can only make antibodies
when it receives the appropriate command signal from a T cell. Once the T
cell signals the B cell with a type of cytokine that acts as a messenger
molecule, the B cell is able to produce a unique antibody that targets a
particular antigen. |
A
T cell sends messenger molecules, e.g. cytokines, to the B cell, which
allows the B cell to start making antibodies. |
Autoantibodies
In some autoimmune diseases, B
cells mistakenly make antibodies against tissues of the body (self
antigens) instead of foreign antigens. Occasionally, these autoantibodies
either interfere with the normal function of the tissues or initiate
destruction of the tissues. People with myasthenia gravis experience
muscle weakness because autoantibodies attack a part of the nerve that
stimulates muscle movement. In the skin disease pemphigus vulgaris,
autoantibodies are misdirected against cells in the skin. The accumulation
of antibodies in the skin activates other molecules and cells to break
down, resulting in skin blisters.
Immune Complexes and the
Complement System
When many antibodies are bound to antigens in the
bloodstream, they form a large lattice network called an immune complex.
Immune complexes are harmful when they accumulate and initiate
inflammation |
A large immune complex. |
within small blood vessels that nourish tissues. Immune
complexes, immune cells, and inflammatory molecules can block blood flow
and ultimately destroy organs such as the kidney. This can occur in people
with systemic lupus erythematosus. |
If immune complexes accumulate in the kidney, they may
promote movement of other inflammatory cells and molecules into the
kidney. |
A group of specialized molecules that form the
complement system helps to remove immune complexes. The different types of
molecules of the complement system, which are found in the bloodstream and
on the surfaces of cells, make immune complexes more soluble. Complement
molecules prevent formation and reduce the size of immune complexes so
they do not accumulate in the wrong places (organs and tissues of the
body). Rarely, some people inherit defective genes for a complement
molecule from their parents. Because these individuals cannot make a
normal amount or type of complement molecule, their immune systems are
unable to prevent immune complexes from being deposited in different
tissues and organs. These people develop a disease that is not autoimmune
but resembles lupus erythematosus.
Genetic
Factors
Genetic factors can affect an individual's immune system
and its responses to foreign antigens in several ways. Genes determine the
variety of MHC molecules that individuals carry on their cells. Genes also
influence the potential array of T-cell receptors present on T cells. In
fact, some MHC genes are associated with autoimmune diseases. However,
genes are not the only factors involved in determining a person's
susceptibility to an autoimmune disease. For example, some individuals who
carry disease-associated MHC molecules on their cells will not develop an
autoimmune disease. |
How Are Autoimmune Diseases Diagnosed?
The diagnosis of an autoimmune disease is based on an individual's
symptoms, findings from a physical examination, and results from
laboratory tests. Autoimmune diseases can be difficult to diagnose,
particularly early in the course of the disease. Symptoms of many
autoimmune diseases—such as fatigue—are nonspecific. Laboratory test
results may help but are often inadequate to confirm a diagnosis.
If an individual has skeletal symptoms such as joint pain and a
positive but nonspecific lab test, she or he may be diagnosed with the
confusing name of early or "undifferentiated" connective tissue disease.
In this case, a physician may want the patient to return frequently for
follow up. The early phase of disease may be a very frustrating time for
both the patient and physician. On the other hand, symptoms may be
short-lived, and inconclusive laboratory tests may amount to nothing of a
serious nature.
In some cases, a specific diagnosis can be made. A
diagnosis shortly after onset of a patient's symptoms will allow for early
aggressive medical therapy; and for some diseases, patients will respond
completely to treatments if the reason for their symptoms is discovered
early in the course of their disease.
Although autoimmune diseases
are chronic, the course they take is unpredictable. A doctor cannot
foresee what will happen to the patient based on how the disease starts.
Patients should be monitored closely by their doctors so environmental
factors or triggers that may worsen the disease can be discussed and
avoided and new medical therapy can be started as soon as possible.
Frequent visits to a doctor are important in order for the physician to
manage complex treatment regimens and watch for medication side effects.
|
How Are Autoimmune Diseases Treated?
Autoimmune diseases are often chronic, requiring lifelong care and
monitoring, even when the person may look or feel well. Currently, few
autoimmune diseases can be cured or made to "disappear" with treatment.
However, many people with these diseases can live normal lives when they
receive appropriate medical care.
Physicians most often help
patients manage the consequences of inflammation caused by the autoimmune
disease. For example, in people with Type 1 diabetes, physicians prescribe
insulin to control blood sugar levels so that elevated blood sugar will
not damage the kidneys, eyes, blood vessels, and nerves. However, the goal
of scientific research is to prevent inflammation from causing destruction
of the insulin-producing cells of the pancreas, which are necessary to
control blood sugars.
On the other hand, in some diseases such as
lupus or rheumatoid arthritis, medication can occasionally slow or stop
the immune system's destruction of the kidneys or joints. Medications or
therapies that slow or suppress the immune system response in an attempt
to stop the inflammation involved in the autoimmune attack are called
immunosuppressive medications. These drugs include corticosteroids
(prednisone), methotrexate, cyclophosphamide, azathioprine, and
cyclosporin. Unfortunately, these medications also suppress the ability of
the immune system to fight infection and have other potentially serious
side effects.
In some people, a limited number of
immuno-suppressive medications may result in disease remission. Remission
is the medical term used for "disappearance" of a disease for a
significant amount of time. Even if their disease goes into remission,
patients are rarely able to discontinue medications. The possibility that
the disease may restart when medication is discontinued must be balanced
with the long-term side effects from the immunosuppressive medication.
A current goal in caring for patients with autoimmune diseases is
to find treatments that produce remissions with fewer side effects. Much
research is focused on developing therapies that target various steps in
the immune response. New approaches such as therapeutic antibodies against
specific T cell molecules may produce fewer long-term side effects than
the chemotherapies that now are routinely used.
Ultimately,
medical science is striving to design therapies that prevent autoimmune
diseases. To this end, a significant amount of time and resources are
spent studying the immune system and pathways of
inflammation.
|
What Are Some Examples of Autoimmune Diseases?
Rheumatoid Arthritis
In people with rheumatoid arthritis, the
immune system predominantly targets the lining (synovium) that covers
various joints. Inflammation of the synovium is usually symmetrical
(occurring equally on both sides of the body) and causes pain, swelling,
and stiffness of the joints. These features distinguish rheumatoid
arthritis from osteoarthritis, which is a more common and degenerative
"wear-and-tear" arthritis. |
An inflamed joint—the synovium—is attacked by
cells and molecules of the immune system. |
Currently available therapy focuses on reducing
inflammation of the joints with anti-inflammatory or immunosuppresssive
medications. Sometimes, the immune system may also target the lung, blood
vessels, or eye; occasionally patients may also develop symptoms of other
autoimmune diseases such as Sjogren's the inflammation, itching, and
scaling. For more severe cases, oral medications are used. Psoriasis is
common and may affect more than 2 out of 100 Americans. Psoriasis often
runs in families.
Multiple Sclerosis
Multiple sclerosis
is a disease in which the immune system targets nerve tissues of the
central nervous system. Most commonly, damage to the central nervous
system occurs intermittently, allowing a person to lead a fairly normal
life. At the other extreme, the symptoms may become constant, resulting in
a progressive disease with possible blindness, paralysis, and premature
death. Some medications such as beta interferon are helpful to people with
the intermittent form of multiple sclerosis.
In young adults,
multiple sclerosis is the most common disabling disease of the nervous
system. Multiple sclerosis afflicts 1 in 700 people in this country.
Researchers continue to search for triggers of the disease.
Immune-Mediated or Type 1 Diabetes Mellitus
Type 1
diabetes mellitus results from autoimmune destruction of the
insulin-producing cells of the pancreas. Insulin is required by the body
to keep the blood sugar (glucose) level under control. High levels of
glucose are responsible for the symptoms and the complications of the
disease. However, most of the insulin-producing cells are destroyed before
the patient develops symptoms of diabetes. Symptoms include fatigue,
frequent urination, increased thirst, and possible sudden confusion.
Type 1 diabetes mellitus is usually diagnosed before the age of 30
and may be diagnosed as early as the first month of life. Together with
Type 2 diabetes (not considered an autoimmune disease), diabetes mellitus
is the leading cause of kidney damage, loss of eyesight, and leg
amputation. Close control of sugar levels decreases the rate at which
these events occur. There is a genetic predisposition to Type 1 diabetes,
which occurs in 1 out of 800 people in the United States. Among
individuals who have a close relative with Type 1 diabetes, those at high
risk for developing disease can be identified. Efforts are now under way
to evaluate prevention strategies for these family members at
risk.
Inflammatory Bowel Diseases
This medical term is used for
both Crohn's disease and ulcerative colitis, two diseases in which the
immune system attacks the gut (intestine). Patients may have diarrhea,
nausea, vomiting, abdominal cramps, and pain that can be difficult to
control. Illness in afflicted individuals can result from intestinal
inflammation and from side effects of the drugs used for the disease. For
example, daily use of high-dose corticosteroid (prednisone) therapy, which
is needed to control severe symptoms of Crohn's disease, can predispose
patients to infections, bone thinning (osteoporosis), and fractures. For
patients with ulcerative colitis, surgical removal of the lower intestine
(colon) will eliminate the disease and their increased risk for colon
cancer. More than 1 in 500 Americans has some type of inflammatory bowel
disease.
Systemic Lupus Erythematosus
Patients with
systemic lupus erythematosus most commonly experience profound fatigue,
rashes, and joint pains. In severe cases, the immune system may attack and
damage several organs such as the kidney, brain, or lung. For many
individuals, symptoms and damage from the disease can be controlled with
available anti-inflammatory medications. However, if a patient is not
closely monitored, the side effects from the medications can be quite
serious. Lupus occurs in 1 out of 2,000 Americans and in as many as 1 in
250 young, African-American women. |
Sunlight is one of the triggers of lupus and can worsen
the progression of the disease. |
Psoriasis
Psoriasis is an immune system
disorder that affects the skin, and occasionally the eyes, nails, and
joints. Psoriasis may affect very small areas of skin or cover the entire
body with a buildup of red scales called plaques. The plaques are of
different sizes, shapes, and severity and may be painful as well as
unattractive. Bacterial infections and pressure or trauma to the skin can
aggravate psoriasis. Most treatments focus on topical skin care to relieve
the inflammation, itching, and scaling. For more severe cases, oral
medications are used. Psoriasis is common and may affect more than 2 out
of 100 Americans. Psoriasis often runs in families.
Scleroderma
This autoimmune disease results in
thickening of the skin and blood vessels. Almost every patient with
scleroderma has Raynaud's, which is a spasm of the blood vessels of the
fingers and toes. Symptoms of Raynaud's include increased sensitivity of
the fingers and toes to the cold, changes in skin color, pain, and
occasionally ulcers of the fingertips or toes. In people with scleroderma,
thickening of skin and blood vessels can result in loss of movement and
shortness of breath or, more rarely, in kidney, heart, or lung failure.
The estimated number of people with any type of scleroderma varies from
study to study but may range from 1 to 4 affected individuals for every
10,000 Americans (or as many as 1 out of 2500 individuals).
Autoimmune Thyroid Diseases
Hashimoto's thyroiditis and
Grave's disease result from immune system destruction or stimulation of
thyroid tissue. Symptoms of low (hypo-) or overactive (hyper-) thyroid
function are nonspecific and can develop slowly or suddenly; these include
fatigue, nervousness, cold or heat intolerance, weakness, changes in hair
texture or amount, and weight gain or loss. The diagnosis of thyroid
disease is readily made with appropriate laboratory tests. |
The thyroid gland affect many parts of the
body. |
The symptoms of hypothyroidism are controlled with
replacement thyroid hormone pills; however, complications from over- or
under-replacement of the hormone can occur. Treatment of hyperthyroidism
requires long-term anti-thyroid drug therapy or destruction of the thyroid
gland with radioactive iodine or surgery. Both of these treatment
approaches carry certain risks and long-term side effects. Autoimmune
thyroid diseases afflict as many as 4 out of 100 women and are frequently
found in families where there are other autoimmune diseases. |
What Research Is Under Way on Autoimmune
Diseases?
The National Institute of Allergy and Infectious Diseases (NIAID)
supports research studies on the function of the immune system in various
diseases. A basic understanding of the human immune system is central to
the understanding of the development of an autoimmune disease (disease
pathogenesis). Scientists searching for ways to prevent and treat
autoimmune disease are studying disease pathogenesis and investigating new
ways to modify the immune system.
Specifically, investigators
supported by NIAID are focusing on: 1) studies of the immune system during
the progression of an autoimmune disease; 2) analysis of the influence of
genetics on autoimmune disease expression and progression; 3) the role of
infectious agents in autoimmune diseases; 4) studies of animal models of
autoimmune diseases; and 5) the effects of therapeutic intervention on the
immune system in an autoimmune disease.
In addition, studies of a
specific autoimmune disease such as multiple sclerosis can provide new and
additional insights into the pathogenesis of autoimmune diseases affecting
other organ systems. Therefore, NIAID also supports studies on specific
autoimmune diseases in cooperation with other Institutes of the National
Institutes of Health that focus on organ-specific autoimmune
diseases.
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