Immune disorders affect the immune system, a complex system that defends the
body against foreign or dangerous invaders. Such invaders include microorganisms
(commonly called germs, such as bacteria and viruses), parasites, cancer cells,
and even transplanted organs and tissues. To defend the body against these invaders,
the immune system must be able to distinguish between what belongs in the body (self)
and what does not (nonself or foreign). Any substances that are identified as nonself
stimulate an immune response in the body. Such substances are called antigens.
Antigens may be contained within or on bacteria, viruses, other microorganisms, or
cancer cells. Antigens may also exist on their own—for example, as food molecules or
pollen. A normal immune response consists of recognizing a potentially harmful foreign
antigen, activating and mobilizing forces to defend against it, and attacking it. If
the immune system malfunctions and mistakes self for nonself, it may attack the body's
own tissues, causing an autoimmune disorder, such as rheumatoid arthritis, thyroiditis,
or lupus.
The immune system is a remarkably effective structure that incorporates
specificity, inducibility and adaptation. Failures of host defense do occur,
however, and fall into three broad categories: immunodeficiencies, autoimmunity,
and hypersensitivities.
Immunodeficiencies
Immunodeficiencies occur when one or more of the components of the immune system
are inactive. The ability of the immune system to respond to pathogens is
diminished in both the young and the elderly, with immune responses beginning to
decline at around 50 years of age due to immunosenescence. In developed
countries, obesity, alcoholism, and drug use are common causes of poor immune
function.
Malnutrition is, however, the most common cause of immunodeficiency in
developing countries. Diets lacking sufficient protein are associated with
impaired cell-mediated immunity, complement activity, phagocyte function, IgA
antibody concentrations, and cytokine production. Deficiency of single nutrients
such as iron; copper; zinc; selenium; vitamins A, C, E, and B6; and folic acid
(vitamin B9) also reduces immune responses. Additionally, the loss of the thymus
at an early age through genetic mutation or surgical removal will result in
severe immunodeficiency and a high susceptibility to infection.
Immunodeficiencies can also be inherited or acquired. Chronic granulomatous
disease, where phagocytes have a reduced ability to destroy pathogens, is an
example of an inherited, or congenital, immunodeficiency. AIDS and some types of
cancer cause acquired immunodeficiency.
Immunodeficiencies can be divided into subgroups based on the component of the
immune system that is affected:
Primary immunodeficiency (PID)
- Primary immunodeficiency occurs when part of a person’s immune system is
missing or does not work correctly. The bodies of people with primary
immunodeficiency can't get rid of germs or protect themselves from new germs as
well as they should. A number of rare diseases feature a heightened
susceptibility to infections from childhood onward.
Many of these disorders are hereditary and are autosomal recessive or X-linked.
There are over 100 recognized primary immunodeficiency syndromes; they are
generally grouped by the part of the immune system that is malfunctioning,
such as lymphocytes or granulocytes.
Symptoms may include:
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Most commonly, a greater likelihood in getting infections
than other people are. |
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Having infections more often and getting infections that are
more severe, longer lasting, and harder to cure than for
people with normal immune systems. |
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Getting infected with germs that a healthy immune system
would be able to get rid of, known as "opportunistic
infections". |
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Having autoimmune problems, meaning that instead of the
immune system attacking germs and disease-causing materials,
it attacks the body’s own organs and tissues by mistake. |
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The treatment of primary immunodeficiencies depends on the nature of the defect,
and may involve antibody infusions, long-term antibiotics and in some cases,
stem cell transplantation.
Acquired immunodeficiency
- Immune deficiency may also be the result of particular external processes or
diseases; the resultant state is called "secondary" or "acquired"
immunodeficiency. Common causes for secondary immunodeficiency are malnutrition,
aging and particular medications (e.g. chemotherapy, disease-modifying
antirheumatic drugs, immunosuppressive drugs after organ transplants,
glucocorticoids).
Many specific diseases directly or indirectly impair the immune system. This
includes many types of cancer, particularly those of the bone marrow and blood
cells (leukemia, lymphoma, multiple myeloma), and certain chronic infections.
Immunodeficiency is also the hallmark of acquired immunodeficiency syndrome
(AIDS), caused by the human immunodeficiency virus (HIV). HIV directly infects a
small number of T helper cells, and also impairs other immune system responses
indirectly.
Some medicines suppress the immune system. One of the drawbacks of chemotherapy
treatment for cancer, for example, is that it not only attacks cancer cells, but
other fast-growing, healthy cells, including those found in the bone marrow and
other parts of the immune system. In addition, people with autoimmune disorders
or who have had organ transplants may need to take immunosuppressant
medications, which also can reduce the immune system's ability to fight
infections and can cause secondary immunodeficiency.
Autoimmunity
Overactive immune responses comprise the other end of immune dysfunction,
particularly the autoimmune disorders. Here, the immune system fails to properly
distinguish between self and non-self, and attacks part of the body. Under
normal circumstances, many T cells and antibodies react with "self" peptides.
One of the functions of specialized cells (located in the thymus and bone
marrow) is to present young lymphocytes with self antigens produced throughout
the body and to eliminate those cells that recognize self-antigens, preventing
autoimmunity.
Autoimmune diseases can be broadly divided into systemic and organ-specific or
localized autoimmune disorders, depending on the principal clinico-pathologic
features of each disease.
Systemic autoimmune
diseases include SLE, Sjögren's syndrome, scleroderma, rheumatoid arthritis,
and dermatomyositis. These conditions tend to be associated with autoantibodies
to antigens which are not tissue specific. Thus although polymyositis is more or
less tissue specific in presentation, it may be included in this group because
the autoantigens are often ubiquitous t-RNA synthetases.
Local syndromes
may be endocrinologic (diabetes mellitus type 1, Hashimoto's thyroiditis,
Addison's disease etc.), dermatologic (pemphigus vulgaris), or hematologic
(autoimmune hemolytic anemia), and involve a specific tissue.
Using the traditional "organ specific" and "non-organ specific" classification
scheme, many diseases have been lumped together under the autoimmune disease
umbrella. However, many chronic inflammatory human disorders lack the telltale
associations of B and T cell driven immunopathology. In the last decade it's
been firmly established that tissue "inflammation against self" doesn't
necessarily rely on abnormal T and B cell responses.
This has led to the recent proposal that the spectrum of autoimmunity should be
viewed along an "immunological disease continuum," with classical autoimmune
diseases at one extreme and diseases driven by the innate immune system at the
other extreme. Within this scheme, the full spectrum of autoimmunity can be
included. Many common human autoimmune diseases can be seen to have a
substantial innate immune mediated immunopathology using this new scheme. This
new classification scheme has implications for understanding disease mechanisms
and for therapy development.
Major autoimmune conditions would include but not limited to:
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In Graves disease, the thyroid gland is stimulated and enlarged, resulting
in high levels of thyroid hormones called hyperthyroidism. It's the most
common cause of hyperthyroidism. It's caused by an abnormal immune system
response that causes the thyroid gland to produce too much thyroid hormones.
Graves disease is most common in women over age 20. However, the disorder
may occur at any age and may affect men as well. |
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Human immunodeficiency virus (HIV) is the virus that causes AIDS. HIV/AIDS
weakens a person's ability to fight infections and cancer. HIV transmission
can occur with unprotected sex or with needle sharing, and also through blood
transfusions. Symptoms of HIV vary widely and a person may have HIV symptoms or
AIDS symptoms without knowing it until they get HIV testing. |
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Lupus is an autoimmune disease that causes inflammation which causes swelling,
pain, and tissue damage throughout the body. If you develop severe lupus, you
may have problems with your kidneys, heart, lungs, nervous system, or blood
cells. Lupus occurs more frequently in women than it does in men, though it
isn't clear why. Four types of lupus exist (systemic lupus erythematosus,
discoid lupus erythematosus, drug-induced lupus erythematosus and neonatal
lupus). Of these, systemic lupus erythematosus is the most common and serious
form of lupus. |
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Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized
by varying degrees of weakness of the skeletal (voluntary) muscles of the
body. Symptoms inclue muscle weakness that increases during periods of activity
and improves after periods of rest. It's caused by a defect in the transmission
of nerve impulses to muscles. It occurs when normal communication between the
nerve and muscle is interrupted at the neuromuscular junction (where nerve cells
connect with the muscles they control).
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Rheumatoid arthritis (RA) occurs when the immune system goes haywire and begins
attacking joint linings. It's a chronic inflammatory condition that also
affects other tissue, but the joints are usually the most severely affected. As
it develops, some of the body's immune cells recognize a protein as a foreign
intruder. The exact protein is unknown, but cells called lymphocytes then react
to the protein. The reaction then causes the release of cytokines, which are
chemical messengers that trigger more inflammation and destruction. With RA, the
main target of inflammation is the synovium, the thin membrane that lines the
joints. The inflammation also goes to other areas in the body causing joint damage,
inflammation, chronic pain, fatigue, and loss of function. |
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Diabetes mellitus type 1 (Type 1 diabetes, IDDM, or juvenile diabetes) is a form
of diabetes mellitus that results from autoimmune destruction of insulin-producing
beta cells of the pancreas. The subsequent lack of insulin leads to increased blood
and urine glucose. Type 1 diabetes is fatal unless treated with insulin. Injection
is the most common method of administering insulin. |
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Most likely not in this category but worth mentioning is Crohn's. It's a disorder
of uncertain etiology. It has often been thought of as an autoimmune disease but
research suggests that the chronic inflammation may not be due to the immune system
attacking the body itself, but rather a result of the immune system attacking harmless
virus, bacteria or food in the gut causing inflammation that leads to bowel injury.
Crohn's disease can cause other parts of the body to become inflamed (due to chronic
inflammatory activity) including the joints, eyes, mouth, and skin. |
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Hypersensitivity
In hypersensitivity (allergic reactions), the immune system is ineffective,
erratically targeting innocent proteins. Hypersensitivity is caused by a defect
in the immune system's functional properties similar to the defect seen in
acquired and other immune deficiency syndromes. In hypersensitivity reactions,
the immune system overreacts. In immune deficiency syndromes, the immune system
under-reacts. Allergic reactions (hypersensitivity reactions) are inappropriate
responses of the immune system to a normally harmless substance.
Normally, the immune system—which includes antibodies, white blood cells, mast
cells, complement proteins, and other substances—defends the body against
foreign substances (called antigens). However, in susceptible people, the immune
system can overreact when exposed to certain chemicals (allergens) in the
environment, foods, or drugs, which are harmless in most people. The result is
an allergic reaction.
Hypersensitivity is an immune response that damages the body's own tissues. They
are divided into four types or classes (Type I – IV) based on the mechanisms involved and
the time course of the hypersensitive reaction.
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Types of Hypersensitivity Reactions |
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Type I or Immediate Hypersensitivity |
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Type II or Cytotoxic (capable
of destroying cells) Hypersensitivity |
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Type III or Immune Complex Hypersensitivity |
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Type IV or Delayed Hypersensitivity |
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Each subtype plays a role in autoimmune disease, with the type of reaction
triggering the type of disorder that occurs. For instance, in immune complex
reactions, complexes of antigens and antibodies lodge into kidney tissue, which
leads to kidney damage.
Type I
hypersensitivity is an immediate or anaphylactic reaction, often associated
with allergy. Symptoms can range from mild discomfort to death. In type I
hypersensitivity reactions, the reaction is immediate and related to the
production of immunoglobulin E. Immunoglobulin E, upon entering the blood
circulations, latches on to mast cells, which produce histamine. Histamine then
induces allergy-associated symptoms. Examples include reactions to penicillin,
insect bites and molds.
Type II
hypersensitivity occurs when antibodies bind to antigens on the patient's own
cells, marking them for destruction. This is also called antibody-dependent (or
cytotoxic) hypersensitivity, and is mediated by IgG and IgM antibodies. Type II
hypersensitivity or cytotoxic hypersensitivity is caused by antibody-mediated
reactions. When the immune system reacts to antigens it produces various
immunoglobulin's or antibodies, usually long-lasting immunoglobulin G (IgG)
antibodies. In type II hypersensitivity reactions K cells rather than mast cells
are involved and complement production increases. These changes injure tissue
cells.
Type III
or complex hypersensitivity reactions are triggered by immune complexes
(aggregations of antigens, complement proteins, and IgG and IgM antibodies)
deposited in various tissues. Type III hypersensitivity is characterized by
circulating autoantibodies that are linked to targeted antigens. These immune
complexes can lodge between tissue cells and interfere with the function of the
affected organ. Immune complexes are responsible for lupus nephritis in several
autoimmune conditions, including systemic lupus erythematosus.
Type IV
hypersensitivity (also known as cell-mediated or delayed type hypersensitivity)
usually takes between 2 and 3 days to develop. Type IV reactions are
involved in many autoimmune and infectious diseases, but may also involve
contact dermatitis (like poison ivy). These reactions are mediated by T cells,
monocytes, and macrophages. Type IV hypersensitivity reactions are delayed
reactions in which the immune system's response to specific antigens is slow,
typically occurring 1 to 2 days after the antigenic exposure. An example is the
delayed rash that can occur 2 days after receiving an inoculation of tuberculin
in the tuberculosis skin test.
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