The immune system protects the body from harmful invaders. However, this protective response can sometimes become exaggerated or inappropriate, reacting to otherwise harmless substances. These overreactions are known as hypersensitivity reactions, broadly categorized into four types. Type IV hypersensitivity is unique due to its delayed, cell-mediated response, distinguishing it from immediate allergic reactions.
Understanding Type IV Hypersensitivity
Type IV hypersensitivity, also known as Delayed-Type Hypersensitivity (DTH) or cell-mediated hypersensitivity, differs from other hypersensitivity reactions because it is mediated by T cells rather than antibodies. This distinct mechanism leads to its characteristic delayed onset, with symptoms typically appearing 24 to 72 hours after exposure to the antigen. The delay occurs because T cells need time to migrate to the exposure site and mount a response.
Unlike immediate, antibody-mediated reactions, Type IV responses involve specific subsets of T lymphocytes, including CD4+ helper T cells and CD8+ cytotoxic T cells. This cell-mediated response plays a role in chronic inflammatory diseases and certain autoimmune conditions. The timing of symptom onset in Type IV reactions can vary based on the number of activated T cells present.
The Cellular Process of Type IV Reactions
Type IV Hypersensitivity reactions involve two primary phases: sensitization and elicitation. The sensitization phase begins when the body first encounters an antigen, such as a chemical, microbe, or transplanted organ component. Antigen-presenting cells (APCs), like dendritic cells or macrophages, process this antigen.
APCs present antigen fragments on their surface, specifically within major histocompatibility complex (MHC) class II molecules, to naive T cells. This activates the T cells, leading to their differentiation into effector T cells, such as Th1 cells or cytotoxic T lymphocytes (CTLs). These activated T cells then proliferate, creating a population of memory cells specific to that antigen.
Upon subsequent exposure to the same antigen, the elicitation phase begins. Activated memory T cells migrate to the site of antigen re-exposure. There, Th1 cells release cytokines, including interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). These cytokines recruit and activate other immune cells, notably macrophages, which contribute to inflammation and tissue damage. Concurrently, cytotoxic T cells directly identify and eliminate target cells presenting the antigen, causing cell lysis and tissue injury.
Everyday Examples of Type IV Reactions
Type IV Hypersensitivity reactions appear in several common forms. A common example is contact dermatitis, which occurs when the skin contacts substances like urushiol from poison ivy, nickel in jewelry, or certain chemicals in cosmetics. The reaction appears as a delayed skin rash, characterized by redness, itching, and sometimes blisters, typically 12 to 48 hours after exposure.
Another example is the tuberculin skin test, also known as the Mantoux test. This diagnostic tool for tuberculosis exposure involves injecting a small amount of tuberculin into the skin. If a person has been previously exposed to Mycobacterium tuberculosis, sensitized T cells react, leading to a localized area of redness and induration (hardening) that peaks within 24 to 72 hours.
Chronic Type IV reactions can also contribute to granuloma formation, which are organized collections of immune cells that wall off persistent antigens. This is seen in diseases like tuberculosis, where immune cells attempt to contain the infection but also cause local inflammation and damage. Additionally, chronic organ transplant rejection can involve a cell-mediated Type IV response, where the recipient’s T cells recognize and attack the transplanted organ’s antigens.
Approaches to Managing Type IV Reactions
Managing Type IV Hypersensitivity reactions primarily involves identifying and avoiding the triggering antigen. For conditions like contact dermatitis, removing exposure to known allergens, such as certain metals or plant resins, can prevent recurrence. For occupational or environmental exposures, protective measures like wearing gloves or specific clothing are recommended.
Pharmacological interventions reduce inflammation and alleviate symptoms. Topical corticosteroids are commonly used for milder skin reactions. For more severe or widespread reactions, or in chronic conditions like certain autoimmune diseases or transplant rejection, systemic immunosuppressants may be prescribed to modulate immune activity.
Supportive care measures can also help with symptomatic relief, addressing discomforts like itching or pain. Consulting a healthcare professional is important for accurate diagnosis and appropriate management, ensuring a tailored treatment plan.