Disorders of the Immune System

Immune system disorders may result from overactivity or underactivity. Allergy and autoimmune diseases fall into the first category; hereditary, infectious, and environmental immune deficiency disease fall into the second.


Allergy involves antigens and antibodies, and its chemical processes are much like those of immunity. Allergy a broader term for which is hypersensitivity can be defined informally as a tendency to react unfavorably to certain substances that are normally harmless to most people. These reaction-producing substances are called allergens, and like most antigens, they are usually proteins. Examples of typical allergens are pollens, house dust, animal dander (dander is the term for the minute scales that are found on hairs and feathers), and certain food proteins. Many drugs can induce allergy, particularly aspirin, barbiturates, and antibiotics (especially penicillin). When a susceptible person’s tissues are repeatedly exposed to an allergen for example, exposure of the nasal mucosa to pollens those tissues become sensitized; that is, antibodies are produced in them. When the next exposure to the allergen occurs, there is an antigen-antibody reaction. Normally, this type of reaction takes place in the blood without harm, as in immunity. In allergy, however, the antigen-antibody reaction takes place within the cells of the sensitized tissues, with results that are disagreeable and sometimes dangerous. In the case of the nasal mucosa that has become sensitized to pollen, the allergic manifestation is hay fever, with symptoms much like those of the common cold. The antigen-antibody reaction in sensitive individuals promotes the release of excessive histamine. Histamine causes dilation and leaking from capillaries as well as contraction of involuntary muscles (e.g., in the bronchi). Antihistamines are drugs that counteract histamine and may be effective in treating the symptoms of certain allergies. Sometimes, it is possible to desensitize an allergic person by repeated intermittent injections of the offending allergen. Unfortunately, this form of protection does not last long. Serum sickness is an example of an allergic manifestation that may occur in response to various sera. People who are allergic to the proteins in serum from a horse or some other animal show such symptoms as fever, vomiting, joint pain, enlargement of the regional lymph nodes, and urticaria, also called hives. This type of allergic reaction can be severe but is rarely fatal.

Anaphylaxis Anaphylaxis is a severe, life-threatening allergic response in a sensitized individual. (The term actually means excess “guarding,” in this case, immune protection, from the Greek word phylaxis.) Any allergen can result in an anaphylactic response, but common causes are drugs, insect venom, and foods. Symptoms appear within seconds to minutes after contact and include breathing problems, swelling of the throat and tongue, urticaria, edema, and decreased blood pressure with cardiovascular shock. Anaphylaxis is treated with injectable epinephrine, antihistamine, administration of oxygen, and plasma expanders to increase blood volume. People subject to severe allergic reactions must avoid contact with known allergens. They should be sensitivity tested before administration of a new drug and should also carry injectable epinephrine and wear a medical bracelet identifying their allergy.

The term autoimmunity refers to an abnormal reactivity to one’s own tissues. In autoimmunity, the immune system reacts to the body’s own antigens, described as “self,” as if they were foreign antigens, or “nonself.” Normally, the immune system learns before birth to ignore (tolerate) the body’s own tissues by eliminating or inactivating those lymphocytes that will attack them. Some factors that might result in autoimmunity include:
* A change in “self” proteins, as a result of disease, for example.
* Loss of immune system control, as through loss of regulatory T cell activity, for example.
* Cross-reaction of antibodies with “self” antigens. This reaction occurs in rheumatic fever, for example, when antibodies to streptococci damage the valves of the heart.
     Autoimmunity is involved in a long list of diseases, including rheumatoid arthritis, multiple sclerosis, lupus erythematosus, psoriasis, inflammatory bowel diseases, Graves disease, glomerulonephritis, and Type I diabetes. All of these diseases probably result to varying degrees from the interaction of individual genetic makeup with environmental factors, including infections. Autoimmune diseases are three times more prevalent in women than in men, perhaps related to hormonal differences. Autoimmunity is treated with drugs that suppress the immune system and with antibodies to lymphocytes. Pure antibodies, such as these, are prepared in the laboratory and are known as monoclonal antibodies. A newer approach uses chemotherapy to destroy immune cells followed by their replacement with healthy stem cells from bone marrow.
Immune Deficiency Diseases
An immune deficiency is some type of failure of the immune system. This failure may involve any part of the system, such as T cells, B cells, or the thymus gland, and it may vary in severity. Such disorders may be congenital (present at birth) or may be acquired as a result of malnutrition, infection, or treatment with x-rays or certain drugs. The disease AIDS (acquired immunodeficiency syndrome) is a devastating example of an infection that attacks the immune system. It is caused by HIV (human immunodeficiency virus), which destroys the specific helper T cells that have a receptor (CD4) for the virus. Its first appearance in the United States in the early 1980s was among homosexual men and injecting drug users. It now occurs worldwide in heterosexual populations of all ages. AIDS is considered to be a pandemic, especially in sub-Saharan Africa and in some parts of Asia. It is spread through unprotected sexual activity and the use of contaminated injection needles. It can also be transmitted from a mother to her fetus. The testing of donated blood has virtually eliminated the spread of AIDS through blood transfusions. Diagnosis of HIV infection is based on the presence of HIV antibodies, the virus, or viral components in the blood. The disease is monitored with CD4 + T cell counts and measurement of HIV RNA in the blood. Patients with AIDS succumb easily to disease, including rare diseases such as parasitic (Pneumocystis) pneumonia and an especially malignant skin cancer, Kaposi sarcoma. Drugs active against HIV stop viral growth at different stages of replication. These drugs, often used in combination, can slow the progress of AIDS, but so far, do not cure it. An obstacle to the development of a vaccine against HIV is the tremendous variability of the virus.
Multiple Myeloma
Multiple myeloma is a cancer of the blood-forming cells in bone marrow, mainly the plasma cells that produce antibodies. These cells produce an excess of a particular antibody, but the antibody is not effective. The disease causes loss of resistance to infection, anemia, bone pain, and weakening of the bones, owing to production of a factor that accelerates loss of bone tissue. High blood levels of calcium and proteins secreted by the plasma cells often lead to kidney failure. Multiple myeloma is treated with chemotherapy. A new approach is high-dose chemotherapy combined with bone marrow transplants. Blood-forming stem cells in the bone marrow replace cells killed by the chemotherapy. This treatment is expensive, and stem cell transplants in themselves are dangerous, but this combined treatment has improved survival rates.

The Immune System and Cancer
Cancer cells differ slightly from normal body cells and therefore the immune system should recognize them as “nonself.” The fact that people with AIDS and other immune deficiencies develop cancer at a higher rate than normal suggests that this is true. Cancer cells probably form continuously in the body but normally are destroyed by NK cells and the immune system, a process called immune surveillance. As a person ages, cell-mediated immunity declines and cancer is more likely to develop. Some efforts are being made to treat cancer by stimulating the patient’s immune system, a practice called immunotherapy. In one approach, T cells have been removed from the patient, activated with interleukin, and then reinjected. This method has given some positive results, especially in treatment of melanoma, a highly malignant form of skin cancer. In the future, a vaccine against cancer may become a reality. Vaccines that target specific proteins produced by cancer cells have already been tested in a few forms of cancer.
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