Hypersensitivity Reaction Definition

A symptomatic interaction between antibodies and allergens that causes an exaggerated and harmful response in the body, commonly called an allergic reaction. Hypersensitivity reactions range from mild to life threatening in severity and symptoms.

ANAPHYLAXIS, the most severe hypersensitivity reaction, is a life-threatening emergency that requires immediate medical attention.

There are four types of hypersensitivity reaction, classified according to the way in which the ALLERGEN or ANTIGEN activates the reaction. The classic allergic reaction is the type I hypersensitivity reaction, with exposure to an external substance (the allergen) initiating the IMMUNE RESPONSE. Types II, III, and IV hypersensitivity reactions are endogenous (within the body) responsible for IMMUNE DISORDERS (other than due to IMMUNODEFICIENCY) and AUTOIMMUNE DISORDERS.

Type I Hypersensitivity Reaction: IgE Antibody Reaction

IMMUNOGLOBULIN E (IgE), the foundation lipoprotein for ANTIBODY formation, mediates type I hypersensitivity reactions. With exposure to an external allergen, the immune response floods the BLOOD circulation with antibodies. Mast cells, basophils, and eosinophils (white blood cells that have specialized immune functions) participate in type I hypersensitivity reactions. Mast cells release HISTAMINEPROSTAGLANDINS, and other biochemicals that set in motion interactions among various proteins and cells that guide further immune activity.

Symptoms generally occur within 15 to 30 minutes of exposure, though sometimes can emerge 10 to 12 hours after exposure. Anaphylaxis (also called anaphylactic shock) is the most severe type I hypersensitivity and is life threatening. ALLERGIC RHINITISALLERGIC CONJUNCTIVITISALLERGIC ASTHMA, ATOPY, and FOOD ALLERGIES are type I hypersensitivity reactions. Type I hypersensitivity reactions tend to run in families, causing researchers to suspect genetic underpinnings for the allergies.

A type I hypersensitivity reaction occurs in two stages: the induction stage, the first exposure during which the IMMUNE SYSTEM produces antibodies for the particular antigen or allergen, and the elicitation stage, during which the immune response activates the antibodies to attack the antigen or allergen. There are no symptoms during the induction stage. Each subsequent exposure to the antigen or allergen triggers the elicitation stage, resulting in symptoms. The elicitation stage lasts as long as there is allergen-antibody interaction, though symptoms may continue for some time (hours to days) afterward.

Regardless of what form symptoms take (SKIN RASH, tingling around the MOUTH, DIARRHEA), a type I hypersensitivity reaction is a systemic response- it affects and involves the body as a whole. Sensitization to an allergen is long term or lifelong because the antibody-bearing PLASMA cells (B-cell lymphocytes that specialize to produce antibodies) circulate indefinitely in the blood.

Type II Hypersensitivity Reaction: Cytotoxic Reaction

Immunoglobulin G (IgG) and immunoglobulin M (IgM) mediate cytotoxic reactions, also called antibody-mediated hypersensitivity reactions. Type II reactions occur as a result of interactions between antibodies and antigens on cell membrane surfaces. The immune response activates the COMPLEMENT CASCADE, which results in the release of biochemicals that kill the antigen-bearing cells. Tcell lymphocytes and natural killer (NK) cells also participate. Symptoms of a type II hypersensitivity reaction typically emerge within a few minutes to several hours after antibody-antigen binding. Hemolytic ANEMIABLOOD TRANSFUSION reactions, Rhesus (Rh) blood reactions (erythroblastosis fetalis), PEMPHIGUS, GOODPASTURE’S SYNDROME, and many DRUG allergies (notably penicillin) are type II hypersensitivity reactions.

Type III Hypersensitivity Reaction: Immune Complex (IC) Reaction

IgG and IgM also mediate type III hypersensitivity reactions, though through different mechanisms from those that occur in type II hypersensitivity reactions. Type III hypersensitivity reactions occur when unattached antigens enter the blood circulation and activate an immune response that results in the formation of an immune complex, a conglomeration of immune proteins (immunoglobulins), platelets, neutrophils, and immune-related substances that surround the antigens. Eventually these clumps fall out of the blood circulation and settle into tissues. Type III antibodies are autoantibodies-that is, antibodies that target the body’s own antigens.

Researchers do not know what precipitates the immune response in most type III reactions, though viruses such as HEPATIS A, serum sickness, and drug reactions are sometimes accountable. Symptoms develop 3 to 10 hours after the immune complex forms. ASPERGILLOSISSYSTEMIC LUPUS ERYTHEMATOSUS (SLE)GLOMERULONEPHRITIS, polyarteritis and other forms of VASCULITIS, and RHEUMATOID ARTHRITIS are type III hypersensitivity reactions.

Type IV Hypersensitivity Reaction: Delayed Reaction

T-cell lymphocytes (primarily helper T-cells) mediate type IV hypersensitivity reactions, also called delayed-type hypersensitivity (DTH) or cell-mediated hypersensitivity reactions. Type IV reactions take days to weeks to manifest. The rash of poison ivy, poison oak, and poison sumac represents a type IV hypersensitivity reaction. GRANULOMA is also a typical type IV hypersensitivity reaction, often to BACTERIA or fungi the body is unable to completely eliminate. Common therapeutic applications of a type IV hypersensitivity reaction include the tuberculin skin test to detect the presence of Mycobacterium tuberculosis and skin patch ALLERGY TESTING.

Symptoms and Diagnostic Path

Symptoms vary with the type and severity of the hypersensitivity reaction. Itching and skin rash or URTICARIA (hives) are common with type I hypersensitivity reactions. Symptoms may involve the airways (allergic asthma) or gastrointestinal tract (food allergies). Contact reactions typically involve the surface of the skin though may also produce widespread systemic symptoms.

The diagnostic path may include blood tests to assess the types and levels of blood cells present in the circulation as well as to detect the types and quantities of immunoglobulins. Allergy testing can help isolate the specific allergens for type I hypersensitivity reactions. The doctor may conduct further diagnostic testing to rule out other possible causes of the symptoms.

Hypersensitivity Reaction Types and Symptoms

Type of ReactionSymptomsTypical Onset from Exposure
type I (IgE antibodies)URTICARIA (hives), SKIN RASH, wheezing itching15 to 30 minutes
type II (cytotoxic)redness and swelling due to cell or tissue deathminutes to several hours
type III (immune complex)redness and swelling (erythema and edema) pain3 to 10 hours
type IV (cell mediated)redness and hardness (erythema and induration)
48 to 72 hours (nongranuloma)
3 to 4 weeks (granuloma)

Treatment Options and Outlook

Antihistamine medications are the most effective intervention early in the onset of a type I hypersensitivity reaction, the classic allergic reaction. These medications block histamine receptors on cell membrane surfaces, effectively breaking the chain reaction effect of the immune response. The longer the hypersensitivity reaction has been under way, the less effective antihistamine medications are because the reaction moves beyond histamine release and binding.

Treatment for anaphylactic symptoms is injection with EPINEPHRINE, a potent NEUROTRANSMITTER and HORMONE that effectively halts the immune response. Doctors reserve epinephrine for life-threatening hypersensitivity reactions because the drug has numerous and significant effects on cardiovascular and pulmonary function.

CORTICOSTEROID MEDICATIONS are effective for severe type I reactions and type II, III, and IV reactions. Other IMMUNOSUPPRESSIVE MEDICATIONS such as methotrexate and cyclosporine act through different mechanisms to interrupt the immune response. DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDS) use various mechanisms to achieve similar results. MONOCLONAL ANTIBODIES (MABS)are showing great promise for treating hypersensitivity reactions in some people. The appropriate treatment selections depend on the type and severity of the hypersensitivity reaction and any other health conditions the person may also have.

Treatment Options For Hypersensitivity Reaction

TreatmentsEffectsEffective for Type of Reaction
CORTICOSTEROID MEDICATIONSsuppress COMPLEMENT CASCADE, ANTIBODY activation, and eosinophil production
suppress mast cell release of histamine, LEUKOTRIENES, and PROSTAGLANDINS
type II, type III, type IV
type I when severe or nonresponsive to other treatment
DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDS)suppress various immune response pathwaystype III
EPINEPHRINE injectionstop the immune responsetype I when severe or anaphylactic
immunosuppressive agents other than corticosteroidssuppress various immune response pathwaystype III and type IV
leukotriene receptor antagonist medicationsblock leukotriene bindingtype I when ASTHMA present
MAST CELL stabilizersprevent degranulation within mast cells to block the release of histamine, leukotrienes, and prostaglandinstype I when asthma present
MONOCLONAL ANTIBODIES (MABS)block antibody-ANTIGEN bindingtype I when asthma present
type III and type IV
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)block the actions of prostaglandinstype III

Risk Factors and Preventive Measures

The sole risk for hypersensitivity reaction (types I, II, and III) is exposure to an allergen; the most effective prevention is avoiding such exposure. This approach is often easier said than done, especially when the allergen is an ubiquitous substance such as pollen or mold. Doctors often recommend taking antihistamine medications on a regular schedule during times when pollen counts are high to reduce hypersensitivity reactions among people who have seasonal allergies. Desensitization effectively reduces or prevents hypersensitivity reactions to specific allergens for many people, providing permanent relief.


Hypersensitivity reaction – types, symptoms, treatment and allergy
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