[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Immunology](https://durgical.com/en/immunology/) › [Innate immunity](https://durgical.com/en/immunology/#a-innate) › Granulomatous inflammation

[Immunology](https://durgical.com/en/immunology/) · [Innate immunity](https://durgical.com/en/immunology/#a-innate)

# Granulomatous inflammation

- Process

When the body cannot destroy something, it walls it off with a ball of activated macrophages: a granuloma.

Updated 2026-11-01

**See it in 3D:** [Mediastinal lymph nodes](https://durgical.com/en/anatomy/mediastinal-lymph-nodes/)

## Key points

- Granuloma = activated macrophages (epithelioid cells) plus giant cells and lymphocytes.
- Th1 axis: IL-12 drives Th1 cells, IFN-γ activates macrophages, TNF maintains the granuloma.
- Caseating: tuberculosis (and some fungi); non-caseating: sarcoidosis, Crohn disease, foreign body.
- Anti-TNF drugs can reactivate latent tuberculosis.
- Sarcoidosis: bilateral hilar lymphadenopathy and possible hypercalcemia.

## What it is

A granuloma is a compact collection of activated macrophages (epithelioid cells), often with multinucleated giant cells and a rim of lymphocytes. It forms when an agent is hard to eliminate, such as mycobacteria, some fungi or inert foreign material, and it depends on a Th1 response (IFN-γ) and TNF. Granulomas with central caseous necrosis suggest tuberculosis; non-caseating granulomas suggest sarcoidosis and other causes.

## Structure

- Center: epithelioid macrophages with pale, elongated nuclei and abundant pink cytoplasm.
- Multinucleated giant cells (Langhans: nuclei in a horseshoe at the edge; foreign-body type: scattered nuclei).
- Rim of lymphocytes (mainly CD4 T cells) and, over time, fibrosis.
- In tuberculosis, a central zone of caseous (cheese-like) necrosis.

## Step by step

- A macrophage takes up a persistent agent and presents its antigens to CD4 T cells.
- Macrophage IL-12 drives the T cells toward the Th1 subset.
- Th1 cells release IFN-γ, which activates macrophages.
- Activated macrophages become epithelioid cells; some fuse into multinucleated giant cells (Langhans type in tuberculosis).
- TNF keeps the structure organized; lymphocytes and later fibroblasts surround it.
- The agent is contained; in tuberculosis the center may undergo caseous necrosis and later calcify.

## Causes of granulomas

| Cause | Typical pattern |
| --- | --- |
| [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/) | Caseating granulomas, often in lung and lymph nodes; Langhans giant cells |
| Leprosy (tuberculoid form) | Well-formed granulomas around skin nerves |
| Endemic fungi (histoplasmosis, paracoccidioidomycosis) | Granulomas in lung and other organs; important in Latin America |
| [Sarcoidosis](https://durgical.com/en/conditions/sarcoidosis/) | Non-caseating granulomas, bilateral hilar lymph nodes |
| [Crohn disease](https://durgical.com/en/conditions/crohn-disease/) | Non-caseating granulomas in the bowel wall |
| [Chronic granulomatous disease](https://durgical.com/en/conditions/chronic-granulomatous-disease/) | Granulomas and abscesses from failed microbial killing |
| Foreign bodies and schistosome eggs | Giant cells around the material or eggs |

## Clinical notes

- Drugs that block TNF can reactivate latent tuberculosis, so latent infection is screened for before they are started.
- Granulomas in sarcoidosis can make 1-alpha-hydroxylase, raising active vitamin D and causing hypercalcemia.
- Defects of the IL-12 or IFN-γ axis cause severe mycobacterial infections, including after BCG vaccination.

## Memory aid

A granuloma is a jail for what cannot be killed: IFN-γ trains the guards (macrophages) and TNF keeps the walls standing.

## Test yourself

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

## Which cytokines are essential to form and maintain a granuloma?

IL-12 to drive Th1 cells, IFN-γ to activate macrophages, and TNF to keep the granuloma organized.

## Which type of granuloma suggests tuberculosis?

A caseating granuloma, with central caseous necrosis and Langhans giant cells.

## Why is latent tuberculosis screened for before starting a TNF inhibitor?

TNF maintains the granulomas that contain the bacilli; blocking it can let latent infection reactivate.

## Why can sarcoidosis cause hypercalcemia?

Activated macrophages in the granulomas produce 1-alpha-hydroxylase, which increases active vitamin D (calcitriol) and intestinal calcium absorption.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/immunology/granulomatous-inflammation/)

## See it in 3D

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

- [Mediastinal lymph nodes](https://durgical.com/en/anatomy/mediastinal-lymph-nodes/)

## Related

- [Th1, Th2, Th17, Tfh and Treg](https://durgical.com/en/immunology/th1-th2-th17-tfh-and-treg/)
- [Phagocytosis and the respiratory burst](https://durgical.com/en/immunology/phagocytosis-and-the-respiratory-burst/)
- [Acute inflammation: vascular and cellular events](https://durgical.com/en/immunology/acute-inflammation-vascular-and-cellular-events/)
- [Monocyte and macrophage](https://durgical.com/en/immunology/monocyte-and-macrophage/)
- [CD4⁺ helper T cell](https://durgical.com/en/immunology/cd4-helper-t-cell/)
- [Interferon-γ](https://durgical.com/en/immunology/interferon/)
- [TNF-α](https://durgical.com/en/immunology/tnf/)
- [IL-12 and IL-23](https://durgical.com/en/immunology/il-12-and-il-23/)
- [Type IV hypersensitivity (delayed, T cells)](https://durgical.com/en/immunology/type-iv-hypersensitivity/)
- [Tuberculin skin test and IGRA](https://durgical.com/en/immunology/tuberculin-skin-test-and-igra/)
- [Phagocyte defects: CGD, LAD, Chédiak–Higashi](https://durgical.com/en/immunology/phagocyte-defects-cgd-lad-chediak-higashi/)

## Related conditions

- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)
- [Sarcoidosis](https://durgical.com/en/conditions/sarcoidosis/)
- [Crohn disease](https://durgical.com/en/conditions/crohn-disease/)
- [Chronic granulomatous disease](https://durgical.com/en/conditions/chronic-granulomatous-disease/)

## Microorganisms

- [Mycobacterium tuberculosis](https://durgical.com/en/microbiology/mycobacterium-tuberculosis/)
- [Mycobacterium leprae](https://durgical.com/en/microbiology/mycobacterium-leprae/)
- [Histoplasma capsulatum](https://durgical.com/en/microbiology/histoplasma-capsulatum/)
- [Paracoccidioides brasiliensis](https://durgical.com/en/microbiology/paracoccidioides-brasiliensis/)
- [Schistosoma mansoni / S. haematobium / S. japonicum](https://durgical.com/en/microbiology/schistosoma-mansoni-s-haematobium-s-japonicum/)

[← 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: [17.5 Inflammation and Fever](https://openstax.org/books/microbiology/pages/17-5-inflammation-and-fever) (OpenStax (Microbiology), 2016); [Sarcoidosis - What Is Sarcoidosis?](https://www.nhlbi.nih.gov/health/sarcoidosis) (National Heart, Lung, and Blood Institute (NHLBI), NIH, 2024).

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Representative model, for educational purposes only.

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