Hypersensitivity Reactions in AD

This article describes the 4 types of hypersensitivity reactions and explains how they contribute to autoimmune disease development and symptoms.

The immune system, when functioning normally, protects us from foreign antigen particles, such as bacteria, viruses, pollen, and toxins. Hypersensitivity is a condition caused by the immune system's inappropriate exaggerated response to these foreign antigens. Hypersensitivity reactions often occur in people with autoimmune diseases, and some hypersensitivity reactions trigger autoimmune disease development. In hypersensitivity the immune system is ineffective, erratically targeting many innocent proteins, including the proteins present in our own cells. 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. However, in hypersensitivity the immune system overreacts, and in immune deficiency syndromes, the immune system fails to react properly even when encountering infectious microorganisms.

There are four different types of hypersensitivity reactions: Type I or Immediate hypersensitivity; Type II or Cytotoxic (capable of destroying cells) hypersensitivity; Type III or Immune complex hypersensitivity; and Type IV or Delayed hypersensitivity. Each of these hypersensitivity reactions plays a role in autoimmune disease, with the type of reaction triggering the type of disorder that occurs. In addition, individuals with autoimmune disease are more likely to experience one or more different types of hypersensitivity reactions. The environmental substances someone will react to and the severity of these reactions are under the control of immune system and organ-specific genes.

Type I Hypersensitivity

In type I hypersensitivity reactions, the reaction is immediate and related to the production of immunoglobulin E. Immunoglobulin E then latches on to mast cells, which produce histamine and allergy-associated symptoms. Examples include reaction to penicillin, insect bites and molds. Common symptoms include hives, itching (urticaria) and swelling of the larynx. Individuals who are hypersensitive to specific allergens are likely to develop anaphylactic reactions when they're exposed to significant amounts of these allergens.

While type I hypersensitivity reactions don't directly cause autoimmune diseases, they stimulate the immune system's and impair its effectiveness. For instance, about 42 percent of patients with autoimmune thyroid disease are likely to have type I hypersensitivity reactions compared to 32 percent of normal subjects. By stimulating the immune system, these reactions can increase autoantibody production in persons with autoimmune disease, exacerbating or worsening symptoms.

Type II Hypersensitivity

Type II hypersensitivity or cytotoxic hypersensitivity is caused by antibody-mediated reactions. When the immune system reacts to antigens it produces various immunoglobulins or antibodies, usually long-lasting immunoglobulin G (IgG) antibodies. In type II hypersensitivity reactions K-cells rather than mast cells are involved and complement is produced. These immune system changes injure tissue cells. Autoimmune diseases mediated by type II hypersensitivity reactions include pemphigus, autoimmune hemolytic anemia (AIHA) and Goodpasture's syndrome.

In pemphigus, IgG antibodies react with the intracellular substances found between the skin's epidermal cells. In AIHA, protein antigens in medications elicit the production of antibodies that destroy red blood cells. In Goodpasture's syndrome, which primarily causes the kidney disease glomerulonephritis, IgG antibodies can destroy the kidney's basement membrane cells.

Type III Hypersensitivity

Type III or complex 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 kidney disease in certain autoimmune conditions, including systemic lupus erythematosus.

Type IV Hypersensitivity

Type IV hypersensitivity reactions are delayed reactions in which the immune system's response to specific antigens is slow to develop, typically causing reactions 1-2 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.

Resource:

Mary L Turgeon, Immunology & Serology in Laboratory Medicine, 2003