A hypersensitivity reaction is an exaggerated response by the immune system to a foreign substance, resulting in tissue damage rather than protection. These reactions are categorized into four main types. Delayed Type Hypersensitivity (DTH) is unique because its effects are not immediately visible upon exposure to the trigger, often taking 24 to 72 hours to manifest. Unlike immediate allergic reactions, this slow onset is due to the nature of the immune cells involved, which require time to migrate and accumulate at the site of the reaction.
How the Immune System Creates the Delay
The DTH reaction is classified as Type IV hypersensitivity, mediated by specific immune cells rather than antibodies. This cell-mediated response begins when a foreign substance, or antigen, is processed by specialized cells at the exposure site. These cells then present the antigen to T lymphocytes, specifically a subset known as \(\text{T}_{\text{H}}1\) cells.
The activated \(\text{T}_{\text{H}}1\) cells initiate the delayed cascade by releasing chemical messengers, including interferon-gamma (\(\text{IFN-}\gamma\)) and tumor necrosis factor-alpha (\(\text{TNF-}\alpha\)). Interferon-gamma activates and recruits macrophages, which are large white blood cells, to the area. The full inflammatory reaction requires the migration of these macrophages, which takes 24 to 72 hours after exposure. Activated macrophages release hydrolytic enzymes and pro-inflammatory substances to destroy the foreign material, leading to localized inflammation, swelling, and tissue damage.
Everyday Examples of DTH Reactions
One frequent manifestation of DTH is allergic contact dermatitis, a skin rash caused by direct contact with a sensitizing substance. Common culprits include the oil urushiol found in poison ivy, nickel in jewelry, and certain chemicals in cosmetics or latex. The reaction is characterized by redness, blistering, and intense itching that appears a day or two after contact.
Allergic contact dermatitis is a true DTH response that requires prior sensitization to the substance, distinguishing it from irritant contact dermatitis, which is a non-allergic, immediate reaction caused by chemical damage to the skin barrier. DTH also plays a role in granulomatous inflammation, which occurs when the immune system attempts to wall off persistent microorganisms, such as the bacteria that cause tuberculosis. Macrophages that cannot eliminate the pathogen fuse together, forming a nodular structure called a granuloma. This process contains the infection but can cause significant localized tissue damage over time.
Identifying DTH Through Skin Testing
DTH is diagnosed using specific skin tests that rely on the delayed immune mechanism. The Patch Test is the standard method for identifying the trigger in allergic contact dermatitis. This test involves applying small patches containing suspected allergens to a patient’s back for 48 hours. The area is examined after the patches are removed, and a final reading is often taken at 72 or 96 hours. A positive result is indicated by localized redness, induration, and swelling, confirming T-cell sensitization to that specific substance.
The Tuberculin Skin Test (TST), also known as the Mantoux or PPD test, screens for previous exposure to the bacteria Mycobacterium tuberculosis. A small amount of purified protein derivative (PPD) is injected just beneath the skin on the forearm. The test must be read by a healthcare professional between 48 and 72 hours later to measure the size of the induration, which is the firm, raised swelling. A significant measurement indicates that the immune system has memory T-cells capable of mounting a DTH response, suggesting past infection.
Treatment and Avoidance Strategies
The most effective management for DTH reactions is preventing contact with the identified trigger. Once the specific allergen is confirmed through testing, strict avoidance prevents future reactions by stopping the T-cells from being reactivated.
For active, symptomatic reactions, medical treatment focuses on reducing inflammation and discomfort. Topical corticosteroids, typically creams or ointments, are the mainstay of treatment for contact dermatitis. These medications suppress the localized immune response, reducing the swelling and redness caused by T-cell activity. In severe or widespread DTH, a short course of systemic corticosteroids may be prescribed to dampen the immune system’s reaction throughout the body.
Traditional antihistamines, which are effective for immediate, antibody-mediated allergies, provide little benefit for DTH symptoms. This limited effectiveness reinforces the distinct cellular mechanism of delayed hypersensitivity, which does not primarily involve the release of histamine.