Hypersensitivity reactions are an immune system overreaction to typically harmless substances, leading to undesirable reactions. Different classifications exist, each with distinct immune mechanisms. This article focuses on Type 4 hypersensitivity, known for its characteristic delayed nature.
Understanding Type 4 Hypersensitivity
Type 4 hypersensitivity (delayed-type hypersensitivity or DTH) is a cell-mediated immune response, unlike antibody-driven types. Specific immune cells, not circulating antibodies, primarily drive the reaction. Its defining feature is delayed onset, with symptoms typically developing 24 to 72 hours after exposure, though some can take weeks. This delayed timing distinguishes it from immediate hypersensitivity reactions.
The Immune Mechanism Behind Type 4 Reactions
The mechanism of a Type 4 hypersensitivity reaction involves two phases: sensitization and elicitation. During sensitization, the immune system first encounters an antigen. Antigen-presenting cells (APCs), like macrophages or dendritic cells, capture and process the substance. They then display antigen fragments on their surface, typically with Major Histocompatibility Complex (MHC) class II molecules, to T lymphocytes.
This activates specific T lymphocytes, particularly CD4+ helper T cells (Th1 cells), which become sensitized. These activated T cells proliferate, expanding the population and developing into long-lasting memory cells.
Upon re-exposure to the antigen, the elicitation phase begins. Memory T cells quickly recognize the antigen presented by APCs at the exposure site. Activated CD4+ T cells release cytokines like interferon-gamma (IFN-γ) and interleukin-2 (IL-2).
These cytokines recruit and activate other immune cells, including macrophages and cytotoxic CD8+ T cells. Activated macrophages release pro-inflammatory factors and enzymes, contributing to tissue damage and inflammation. CD8+ T cells can directly destroy target cells presenting the antigen. The accumulation of these immune cells and their inflammatory mediators leads to the visible signs of the delayed reaction.
Common Manifestations of Type 4 Reactions
Type 4 hypersensitivity reactions cause various common conditions, such as allergic contact dermatitis. This often results from exposure to substances like poison ivy, nickel, or certain cosmetic chemicals. The skin develops a red, itchy, and sometimes blistered rash at the contact site, appearing hours to days after exposure.
The tuberculin skin test (PPD test), used to detect prior tuberculosis exposure, is another classic Type 4 reaction. A small amount of tuberculin protein is injected into the skin. If sensitized, a hardened, raised area (induration) develops at the injection site within 48 to 72 hours, resulting from lymphocyte and macrophage infiltration.
Certain aspects of organ transplant rejection, particularly acute and chronic, also involve Type 4 hypersensitivity. The recipient’s T cells recognize and destroy the transplanted organ’s foreign tissues. Type 1 diabetes, an autoimmune disease, also has a Type 4 component, where T cells mistakenly attack and destroy insulin-producing cells in the pancreas.
Identifying and Managing Type 4 Reactions
For suspected allergic contact dermatitis, patch testing is the primary diagnostic method. Small quantities of potential allergens are applied to the skin, usually on the back, and covered with patches. Sites are examined after 48 hours and again at 72 or 96 hours for localized skin reactions like redness or blistering, indicating sensitivity.
Management of Type 4 hypersensitivity reactions focuses on avoiding the trigger and alleviating symptoms. The most effective approach is to identify and eliminate exposure to the causative substance. For instance, avoiding nickel-containing items is advised for a nickel allergy.
To manage symptoms, topical corticosteroids commonly reduce inflammation and itching, especially in skin reactions like contact dermatitis. For more severe cases, oral corticosteroids may be prescribed. For autoimmune conditions with a Type 4 component, systemic immunosuppressants or biologics might modulate the immune response. Patient education about avoidance and proper medication use is important for management.