Immune Disorders

Immune Disorders

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:

•	Most commonly, a greater likelihood in getting infections than other people are.

•	Having infections more often and getting infections that are more severe, longer lasting, and harder to cure than for people with normal immune systems.

•	Getting infected with germs that a healthy immune system would be able to get rid of, known as "opportunistic infections".

•	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.

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:

•	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.

•	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.

•	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.

•	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).

•	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.

•	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.

•	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.

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.

Types of Hypersensitivity Reactions

•	Type I or Immediate Hypersensitivity
•	Type II or Cytotoxic (capable of destroying cells) Hypersensitivity
•	Type III or Immune Complex Hypersensitivity
•	Type IV or Delayed Hypersensitivity

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.