Type 4 Hypersensitivity: Cell-Mediated Hypersensitivity by

RISK FACTORS

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Type IV Hypersensitivity (Cell-Mediated Hypersensitivity)

Overview: Type IV hypersensitivity, also known as delayed-type hypersensitivity (DTH), is an immune response mediated by T lymphocytes rather than antibodies. It typically develops 24–72 hours after exposure to the antigen. This type of hypersensitivity is important for defense against certain pathogens but can cause tissue damage when overactivated.

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Risk Factors

· Repeated exposure to specific antigens (e.g., chemicals, metals, latex, or drugs)

· Chronic infections such as tuberculosis or leprosy

· Autoimmune disorders (e.g., type 1 diabetes, multiple sclerosis)

· Genetic predisposition to exaggerated T-cell responses

· Occupational exposure (healthcare workers, lab technicians, etc.)

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Cellular Pathophysiology

· Antigen-presenting cells (APCs) such as macrophages or dendritic cells process and present antigens to CD4+ T helper (Th1) cells.

· Sensitized Th1 cells release cytokines like interferon-gamma (IFN-γ) and interleukin-2 (IL-2).

· These cytokines recruit and activate macrophages and cytotoxic T lymphocytes (CD8+ cells).

· Activated immune cells cause inflammation and direct tissue injury, leading to the delayed reaction seen clinically.

· Because antibodies are not involved, it differs from Types I–III hypersensitivities.

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Clinical Manifestations

· Symptoms appear 24–72 hours after antigen exposure.

· Localized redness, swelling, induration, and itching at the site.

· Examples:

o Contact dermatitis (e.g., from poison ivy, nickel, or latex)

o Tuberculin skin test (PPD test) reaction

o Chronic transplant rejection

o Granulomatous inflammation in infections like tuberculosis or sarcoidosis

Clinical manifestations of type iv hypersentivity

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Diagnosis

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Diagnosis

· Patch testing for contact dermatitis

· Tuberculin skin test (Mantoux test) for TB exposure

· Biopsy or histopathology showing T-cell infiltration and macrophage activation

Management and Treatment

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Management & Treatment

· Avoidance of known allergens or antigens

· Topical or systemic corticosteroids to reduce inflammation

· Immunosuppressive therapy in severe or chronic cases

· Education on recognizing and preventing exposure triggers

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MECHANISMS

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Type IV hypersensitivity reaction also known as cell mediated hypersensitivity or delayed type of hypersensitivity is the T lymphocytes mediated destruction of cells along with dendritic cells, macrophages and cytokines playing major roles.
The reaction is mediated by specific subsets of CD4+ helper T cells (Th-1 and Th-17 cells) or by CD8+ cytotoxic T cells.
Type IV hypersensitivity occurs 24 hours after contact with an antigen, usually starting at 2 or 3 days and often last for many days.
For this reason, type IV hypersensitivity reaction is termed as “delayed hypersensitivity”.
Type IV hypersensitivity is unique in that, unlike the first three types of hypersensitivity which are antibody mediated, type IV hypersensitivity is cell mediated and also a delayed reaction.

References

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References

McCance, K. L., & Huether, S. E. (2023). Pathophysiology: The Biologic Basis for Disease in Adults and Children (9th ed.). Elsevier.

National Institutes of Health. (2024). Hypersensitivity reactions overview. MedlinePlus.

Abbas, A. K., Lichtman, A. H., & Pillai, S. (2023). Cellular and Molecular Immunology (10th ed.). Elsevier.