42.15: Disruptions in the Immune System - Hypersensitivities
- Distinguish between the disruptions to the immune system caused by allergies and autoimmunity
Maladaptive immune responses toward harmless foreign substances or self antigens that occur after tissue sensitization are termed hypersensitivities. This can potentially be very dangerous for an individual, as the immune response can be very powerful; it can destroy host tissue if not kept in check. The types of hypersensitivities include immediate, delayed, and autoimmunity hypersensitivities. A large proportion of the population is affected by one or more types of hypersensitivity.
Allergies
The immune reaction that results from immediate hypersensitivities, in which an antibody-mediated immune response occurs within minutes of exposure to a harmless antigen, is called an allergy. In the United States, 20 percent of the population exhibits symptoms of allergy or asthma, whereas 55 percent test positive against one or more allergens. Upon initial exposure to a potential allergen, an allergic individual synthesizes antibodies of the IgE class; this class of antibodies also mediates the immune response to parasitic worms. The constant domain of the IgE molecules interacts with mast cells embedded in connective tissues. This process primes, or sensitizes, the tissue. Upon subsequent exposure to the same allergen, IgE molecules on mast cells bind the antigen via their variable domains, stimulating the mast cell to release the modified amino acids histamine and serotonin. These chemical mediators then recruit eosinophils which mediate allergic responses. The effects of an allergic reaction range from mild symptoms such as sneezing and itchy, watery eyes, to more severe or even life-threatening reactions involving intensely-itchy welts known as hives, airway contraction with severe respiratory distress, and plummeting blood pressure. This extreme reaction is known as anaphylactic shock. If not treated with epinephrine to counter the blood pressure and breathing effects, this condition can be fatal.
Delayed hypersensitivity is a cell-mediated immune response that takes approximately one to two days after secondary exposure for a maximal reaction to be observed. This type of hypersensitivity involves the T H 1 cytokine -mediated inflammatory response. It may manifest as local tissue lesions or contact dermatitis (rash or skin irritation). Delayed hypersensitivity occurs in some individuals in response to contact with certain types of jewelry or cosmetics. It also facilitates the immune response to poison ivy and is the reason why the skin test for tuberculosis results in a small region of inflammation on individuals who were previously exposed to Mycobacterium tuberculosis . Cortisone is typically used to treat such responses as it inhibits cytokine production.
Autoimmunity
Autoimmunity is a type of hypersensitivity to self antigens that affects approximately five percent of the population. Most types of autoimmunity involve the humoral immune response. Antibodies that inappropriately mark self components as foreign are termed autoantibodies. In patients with the autoimmune disease myasthenia gravis, muscle cell receptors that induce contraction in response to acetylcholine are targeted by antibodies. The result is muscle weakness that may include marked difficultly with fine and/or gross motor functions. In systemic lupus erythematosus, a diffuse autoantibody response to the individual’s own DNA and proteins results in various systemic diseases. Systemic lupus erythematosus may affect the heart, joints, lungs, skin, kidneys, central nervous system, or other tissues, causing tissue damage via antibody binding, complement recruitment, lysis, and inflammation.
Autoimmunity can develop with time; its causes may be rooted in molecular mimicry. Antibodies and TCRs may bind self antigens that are structurally similar to pathogen antigens, which the immune receptors first raised. As an example, infection with Streptococcus pyogenes (bacterium that causes strep throat) may generate antibodies or T cells that react with heart muscle, which has a similar structure to the surface of S. pyogenes . These antibodies can damage heart muscle with autoimmune attacks, leading to rheumatic fever. Insulin -dependent (Type 1) diabetes mellitus arises from a destructive inflammatory T H 1 response against insulin-producing cells of the pancreas. Patients with this autoimmunity must be injected with insulin that originates from other sources.
Contributions and Attributions
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Key Points
- While the immune system is normally very tightly controlled to disregard “self” and harmless antigens, a condition known as hypersensitivity can override this control, causing illness and injury to an individual.
- Allergies result when the immune system recognizes harmless antigens, such as pollen or dust; they are characterized by red, swollen eyes, sneezing and itching, and can also encompass more serious symptoms such as anaphylactic shock.
- Autoimmunity occurs when the immune system recognizes “self” antigens and begins attacking them; antibodies that recognize self are termed autoantibodies.
Key Terms
- autoantibody : an antibody formed in response to an agent (autoantigen) produced by the organism itself
- histamine : an amine that causes dilatation of capillaries, contraction of smooth muscle, and stimulation of gastric acid secretion; it is released during allergic reactions