Type 4 Hypersensitivity Reaction

Introduction

• Type 4 hypersensitivity is a T-cell-mediated response, unlike types 1, 2, and 3, which are antibody-mediated (humoral-mediated) responses.
• Involves T helper cells and/or cytotoxic T cells.

Mechanism

1. Exposure Example:

   • Poison ivy exposure leads to type 4 hypersensitivity.
   • Contains urushiol, a compound that binds and alters skin proteins.
   • Altered proteins are recognized as foreign by the immune system.

2. Antigen Presentation:

   • Antigen-presenting cells (APCs) recognize and process altered proteins.
   • APCs present protein portions to naive T helper cells using an MHC class II receptor.

3. T Cell Activation:

   • APCs release cytokines to differentiate naive T helper cells.
   • Release of IL-12 leads to differentiation into Th1 cells, releasing IFN-gamma to activate macrophages.
   • Macrophages release IL-1 and TNF-alpha to recruit leukocytes, performing phagocytosis, and releasing reactive oxygen species causing tissue damage.
   • Release of IL-6 leads to differentiation into TH17 cells, releasing IL-17 to activate neutrophils.

4. Delayed Reaction:

   • Known as delayed type hypersensitivity (DTH) due to the time required for T cell activation and recruitment.
   • Symptoms like vesicular dermatitis appear 24-72 hours after exposure.

Clinical Examples

• Tuberculosis (TB) Skin Test:

  • Used to determine past infection with Mycobacterium tuberculosis.
  • Positive result shows a raised lesion at the injection site.

• Contact Dermatitis:

  • Results from metal allergies (e.g., nickel jewelry) or latex exposure.

Cytotoxic T Cell Involvement

• Direct attack on target cells in some type 4 hypersensitivity reactions.

Examples

• Type 1 Diabetes: Targeting of insulin-secreting beta cells.
• Rheumatoid Arthritis: Targeting of joint tissue.
• Hashimoto's Disease: Targeting of thyroid follicular cells.
• Graft Rejection: Targeting of foreign grafted cells.

Mechanism

• Cytotoxic T cells release a perforin-granzime complex inducing apoptosis in target cells.
• Binding to FAST receptor via FAST ligand also triggers apoptosis.

Review Questions

• Includes self-assessment to test understanding of the material covered.