- Understanding the Immune
System
- Disorders of the
Immune System: Allergy
The most common types of allergic
reactions-hay fever, some kinds of asthma, and hives-are produced when the
immune system response to a false alarm. In a susceptible person, a normally
harmless substance-grass pollen or house dust, for example-is perceived as a
threat and is attacked.
Such allergic reactions are related to the
antibody known as immunoglobulin E. Like other antibodies, each IgE antibody is
specific; one reacts against oak pollen, another against ragweed. The role of
IgE in the natural order is not known, although some scientists suspect that it
developed as a defense against infection by parasitic worms.
The first time an
allergy-prone person is exposed to an allergen, he or she makes large amounts of
the corresponding IgE antibody. These IgE molecules attach to the surfaces of
mast cells (in tissue) or basophils (in the circulation). Mast cells are
plentiful in the lungs, skin, tongue, and linings of the nose and intestinal
tract.
When an IgE antibody siting on a mast cell
or basophil encounters its specific allergen, the IgE antibody signals the mast
cell or basophil to release the powerful chemicals stored within its granules.
These chemicals include histamine, heparin, and substances that activate blood
platelets and attract secondary cells such as eosinophils and neutrophils. The
activated mast cell or basophil also synthesizes new mediators, including
prostaglandins and leukotrienes, on the spot.
It is such chemical mediators that cause
the symptoms of allergy, including wheezing, sneezing, runny eyes and itching.
They can also produce anaphylactic shock, a life-threatening allergic reaction
characterized by swelling of body tissues, including the throat, and a sudden
fall in blood pressure.
Autoimmune
Diseases
Sometimes the immune system's
recognition apparatus breaks down, and the body begins to manufacture
antibodies and T cells directed against the body's own constituents-cells,
cell components, or specific organs. Such antibodies are known as
autoantibodies, and the diseases they produce are called autoimmune diseases.
(Not all autoantibodies are harmful; some types appear to be integral to the
immune system's regulatory scheme.)
Autoimmune reactions
contribute to many enigmatic diseases. For instance, autoantibodies to red
blood cells can cause anemia, autoantibodies to pancreas cells contribute to
juvenile diabetes, and autoantibodies to nerve and muscle cells are found in
patients with the chronic muscle weakness known as myasthenia gravis.
Autoantibody known as rheumatoid factor is common in persons with rheumatoid
arthritis.
Persons with systemic lupus
erythematosus (SLE), whose symptoms encompass many systems, have antibodies to
many types of cells and cellular components. These include antibodies directed
against substances found in the cell's nucleus-DNA, RNA, or proteins-which are
known as antinuclear antibodies, or ANAs. These antibodies can cause serious
damage when they link up with self antigens to form circulating immune
complexes, which become lodged in body tissue and set off inflammatory
reactions (Immune Complex Diseases).
Autoimmune diseases affect the immune
system at several levels. In patients with SLE, for instance, B cells are
hyperactive while suppressor cells are underactive; it is not clear which
defect comes first. Moreover, production of IL-2 is low, while levels of gamma
interferon are high. Patients with rheumatoid arthritis, who have a defective
suppressor T cell system, continue to make antibodies to a common virus,
whereas the response normally shuts down after about a dozen days.
No one knows just what causes an
autoimmune disease, but several factors are likely to be involved. These may
include viruses and environmental factors such as exposure to sunlight,
certain chemicals, and some drugs, all of which may damage or alter body cells
so that they are no longer recognizable as self. Sex hormones may be
important, too, since most autoimmune diseases are far more common in women
than in men.
Heredity also appears to play a role.
Autoimmune reactions, like many other immune responses, are influenced by the
genes of the MHC. A high proportion of human patients with autoimmune disease
have particular histocompatibility types. For example, many persons with
rheumatoid arthritis display the self marker known as HLA-DR4.
Many types of therapies are being used
to combat autoimmune diseases. These include corticosteroids,
immunosuppressive drugs developed as anticancer agents, radiation of the lymph
nodes, and plasmapheresis, a sort of "blood washing" that removes
diseased cells and harmful molecules from the circulation.
Immune Complex
Diseases
Immune complexes are clusters of interlocking antigens and antibodies. Under
normal conditions immune complexes are rapidly removed from the bloodstream by
macrophages in the spleen and Kupffer cells in the liver. In some
circumstances, however, immune complexes continue to circulate. Eventually
they become trapped in the tissues of the kidneys, lung, skin, joints, or
blood vessels. Just where they end up probably depends on the nature of the
antigen, the class of antibody-IgG, for instance, instead of IgM-and the size
of the complex. There they set off reactions that lead to inflammation and
tissue damage.
Immune complexes work their damage in
many diseases. Sometimes, as is the case with malaria and viral hepatitis,
they reflect persistent low-grade infections. Sometimes they arise in response
to environmental antigens such as the moldy hay that causes the disease known
as farmer's lung. Frequently, immune complexes develop in autoimmune disease,
where the continuous production of autoantibodies overloads the immune complex
removal system.
Immunodeficiency
Diseases
Lack of one or more components of the
immune system results in immunodeficiency disorders. These can be inherited,
acquired through infection or other illness, or produced as an inadvertent
side effect of certain drug treatments.
People with advanced cancer may
experience immune deficiencies as a result of the disease process or from
extensive anticancer therapy. Transient immune deficiencies can develop in the
wake of common viral infections, including influenza, infectious
mononucleosis, and measles. Immune responsiveness can also be depressed by
blood transfusions, surgery malnutrition, and stress.
Some children are born with defects in
their immune systems. Those with flaws in the B cell components are unable to
produce antibodies (immunoglobulins). These conditions, known as
agammaglobulinemias or hypogammaglobulinemias, leave the children vulnerable
to infectious organisms; such disorders can be combated with injections of
immunoglobulins.
Other children, whose thymus is either
missing or small and abnormal, lack T cells. The resultant disorders have been
treated with thymic transplants.
Very rarely, infants are born lacking
all the major immune defenses; this is known as severe combined
immunodeficiency disease (SCID). Some children with SCID have lived for years
in germ-free rooms and "bubbles." A few SCID patients have been
successfully treated with transplants of bone marrow (Bone Marrow
Transplants).
The devastating immunodeficiency
disorder known as the acquired immunodeficiency syndrome (AIDS) was first
recognized in 1981. Caused by a virus (the human immunodeficiency virus, or
HIV) that destroys T4 cells and that is harbored in macrophages as well as T4
cells, AIDS is characterized by a variety of unusual infections and otherwise
rare cancers. The AIDS virus also damages tissue of the brain and spinal cord,
producing progressive dementia.
AIDS infections are known as "opportunistic" because they are
produced by commonplace organisms that do not trouble people whose immune
systems are healthy, but which take advantage of the "opportunity"
provided by an immune defense in disarray. The most common infection is an
unusual and life-threatening form of pneumonia caused by a one-celled organism
(a Protozoa) called Pneumocystis carinii. AIDS patients are also susceptible
to unusual lymphomas and Kaposi's sarcoma, a rare cancer that results from the
abnormal proliferation of endothelial cells in the blood vessels.
Some persons infected with the AIDS
virus develop a condition known as AIDS-related complex, or ARC, characterized
by fatigue, fever, weight loss, diarrhea, and swollen lymph glands. Yet other
persons who are infected with the AIDS virus apparently remain well; however,
even though they develop no symptoms, they can transmit the virus to others.
AIDS is a contagious disease, spread by
intimate sexual contact, by direct inoculation of the virus into the
bloodstream, or from mother to child during pregnancy. Most of the AIDS cases
in the United States have been found among homosexual and bisexual men with
multiple sex partners, and among intravenous drug abusers. Others have
involved men who received untreated blood products for hemophilia; persons who
received transfusions of inadvertently contaminated blood-primarily before the
AIDS virus was discovered and virtually eliminated from the nation's blood
supply with a screening test; the heterosexual partners of persons with AIDS;
and children born to infected mothers.
There is presently no cure for AIDS,
although the antiviral agent zidovuzine (AZT) appears to hold the virus in
check, at least for a time. Many other antiretroviral drugs are being tested,
as are agents to bolster the immune system and agents to prevent or treat
opportunistic infections. Research on vaccines to prevent the spread of AIDS
is also under way.
Cancers of the
Immune System
Cells of the immune system, like those
of other body systems, can proliferate uncontrollably; the result is cancer.
Leukemias are caused by the proliferation of white blood cells, or leukocytes.
The uncontrolled growth of antibody-producing (plasma) cells can lead to
multiple myeloma. Cancers of the lymphoid organs, known as lymphomas, include
Hodgkin's disease. These disorders can be treated-some of them very
successfully-by drugs and/or irradiation.
This information is a
collaboration of the National Cancer Institute
and the National Institute of Allergy and Infectious Diseases.
National Institutes of Health
National Cancer Institute
U.S. Department of Health and Human Services
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