[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Immunology](https://durgical.com/en/immunology/) › [Hypersensitivity](https://durgical.com/en/immunology/#a-hypersensitivity) › Type IV hypersensitivity (delayed, T cells)

[Immunology](https://durgical.com/en/immunology/) · [Hypersensitivity](https://durgical.com/en/immunology/#a-hypersensitivity)

# Type IV hypersensitivity (delayed, T cells)

- Process

A slow reaction made by T cells, not antibodies. It shows up two to three days after contact, as in the tuberculin skin test or a rash from nickel.

Updated 2026-11-01

**See it in 3D:** [Skin](https://durgical.com/en/anatomy/skin/)

## Key points

- T cells, not antibodies; cannot be transferred with serum.
- 48–72 hours: tuberculin skin test and contact dermatitis.
- Th1 → interferon-gamma → macrophage activation → granuloma.
- CD8 cytotoxic T cells drive contact dermatitis and Stevens–Johnson syndrome/TEN.
- Anergy (no response to tuberculin) points to weak cellular immunity, as in advanced HIV.

## What it is

Type IV hypersensitivity is the only type driven by T cells instead of antibody. Memory CD4 Th1 cells release interferon-gamma and TNF-alpha that activate macrophages, which can build granulomas; CD8 cytotoxic T cells kill cells that carry the antigen. Because T cells must be recruited and activated at the site, it takes 48–72 hours or longer. It underlies the tuberculin skin test, contact dermatitis, the tuberculosis granuloma and severe drug skin reactions.

## Function

- Th1 cells make interferon-gamma, the main signal that turns macrophages into killers.
- Activated macrophages fuse into giant cells and wall off microbes they cannot destroy (granuloma).
- CD8 T cells kill antigen-bearing cells through perforin and granzymes or Fas ligand.

## Forms of delayed hypersensitivity

| Form | Main cells | Example | Timing |
| --- | --- | --- | --- |
| Tuberculin type | CD4 Th1 cells and macrophages | Tuberculin skin test (PPD) induration | 48–72 hours |
| Contact | CD8 and CD4 T cells in the skin | Contact dermatitis from nickel, fragrances, latex additives or plant oils | 48–72 hours after contact |
| Granulomatous | Th1 cells, epithelioid macrophages, giant cells | Tuberculosis, leprosy, sarcoidosis, Crohn disease | Weeks |
| Severe drug reactions | Cytotoxic T cells (and Th2 cells with eosinophils in DRESS) | Stevens–Johnson syndrome and toxic epidermal necrolysis, DRESS | Days to weeks after starting the drug |

## Clinical notes

- T-cell–mediated autoimmune diseases such as type 1 diabetes and multiple sclerosis use the same effector arm against self antigens.
- A false-negative tuberculin test can occur when T cells are weak: HIV, malnutrition, measles, steroids or other immunosuppression.
- Patch testing reproduces contact dermatitis on the back to identify the allergen.

## In the lab

- Tuberculin skin test read as induration at 48–72 hours; interferon-gamma release assays (IGRA) measure the same T-cell memory in blood.
- Patch test read at 48 hours and again later.

## Memory aid

Type IV takes its time: the T cell has to be called, travel and arrive, so the reaction is read on day two or three.

## Test yourself

Think of the answer, then tap the question to see it.

## Why does the tuberculin skin test take 48–72 hours to read?

Memory Th1 cells must reach the site, recognise the antigen and recruit macrophages; that cellular build-up, not antibody, makes the induration.

## Which cytokine is essential for macrophage activation in granuloma formation?

Interferon-gamma from Th1 cells (with TNF-alpha). Without it, macrophages cannot contain mycobacteria.

## A patient with advanced HIV and active tuberculosis has a negative tuberculin skin test. Why?

The test needs working CD4 T cells. With very low CD4 counts the delayed reaction cannot form (anergy), so the result is falsely negative.

## What test identifies the cause of allergic contact dermatitis?

The patch test: suspected substances are taped to the skin and the site is read about 48 hours later and again after a few days.

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## See it in 3D

The structures of Durgical's 3D anatomy where it is found.

- [Skin](https://durgical.com/en/anatomy/skin/)

## Related

- [Hypersensitivity: the four types compared](https://durgical.com/en/immunology/hypersensitivity-the-four-types-compared/)
- [Th1, Th2, Th17, Tfh and Treg](https://durgical.com/en/immunology/th1-th2-th17-tfh-and-treg/)
- [CD8⁺ cytotoxic T cell](https://durgical.com/en/immunology/cd8-cytotoxic-t-cell/)
- [Monocyte and macrophage](https://durgical.com/en/immunology/monocyte-and-macrophage/)
- [Granulomatous inflammation](https://durgical.com/en/immunology/granulomatous-inflammation/)
- [Tuberculin skin test and IGRA](https://durgical.com/en/immunology/tuberculin-skin-test-and-igra/)
- [Interferon-γ](https://durgical.com/en/immunology/interferon/)
- [Latex and drug allergy](https://durgical.com/en/immunology/latex-and-drug-allergy/)

## Related conditions

- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)
- [Pulmonary tuberculosis](https://durgical.com/en/conditions/pulmonary-tuberculosis/)
- [Type 1 diabetes mellitus](https://durgical.com/en/conditions/type-1-diabetes-mellitus/)
- [Multiple sclerosis](https://durgical.com/en/conditions/multiple-sclerosis/)
- [Crohn disease](https://durgical.com/en/conditions/crohn-disease/)

## Microorganisms

- [Mycobacterium tuberculosis](https://durgical.com/en/microbiology/mycobacterium-tuberculosis/)

[← All of immunology](https://durgical.com/en/immunology/)

Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: [Type IV Hypersensitivity Reaction](https://www.ncbi.nlm.nih.gov/books/NBK562228/) (StatPearls Publishing (NCBI Bookshelf), 2025); [Autoimmune responses are directed against self antigens](https://www.ncbi.nlm.nih.gov/books/NBK27155/) (Garland Science (Janeway's Immunobiology, 5th ed., NCBI Bookshelf), 2001).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/immunology/type-iv-hypersensitivity/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/immunology/type-iv-hypersensitivity/