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

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	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	Non-caseating granulomas, bilateral hilar lymph nodes
Crohn disease	Non-caseating granulomas in the bowel wall
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.

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.

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See it in 3D

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

Mediastinal lymph nodes

Microorganisms

← All of 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 (OpenStax (Microbiology), 2016); Sarcoidosis - What Is Sarcoidosis? (National Heart, Lung, and Blood Institute (NHLBI), NIH, 2024).

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Representative model, for educational purposes only.