Chronic specific (granulomatous) inflammation
Why macrophages wall off what they cannot destroy: how T cells turn them into the epithelioid and giant cells of a granuloma, how the types differ, and what tuberculosis, leprosy and syphilis teach about immunity.
By the end, you can
- Explain why a granuloma forms and the roles of Th1 cells, interferon-gamma and TNF.
- Describe the cells of a granuloma and distinguish epithelioid cells, Langhans and foreign-body giant cells.
- Compare immune and foreign-body granulomas, and caseating and non-caseating granulomas, with examples.
- Relate the classic "specific" infections (tuberculosis, leprosy, syphilis, rhinoscleroma) to the granulomas they produce.
- Explain how granulomas contain an agent yet damage organs, and why containment can fail.
- Recognise the classic appearances, causes and tests of granulomas, including special stains and interferon-gamma release assays, and explain how treating the cause, glucocorticoids and other immunosuppressants act on them.
What it is
Granulomatous inflammation is a pattern of chronic inflammation in which activated macrophages, called epithelioid cells, gather into compact nodules (granulomas), often with multinucleated giant cells and a rim of lymphocytes, around an agent the body cannot remove. Many European curricula call the infections that produce characteristic granulomas (tuberculosis, leprosy, syphilis and rhinoscleroma) chronic specific inflammation, because the tissue pattern can point towards the cause.
3 types to tell apart
- Immune granulomas
- Driven by T cells responding to a persistent antigen: mycobacteria, Treponema pallidum, some fungi, and unknown antigens in sarcoidosis and Crohn’s disease.
- Foreign-body granulomas
- Macrophages surround inert material too large to engulf (sutures, talc, splinters, keratin, urate crystals), with little T-cell involvement.
- Caseating and non-caseating
- Caseating (necrotising) granulomas have a soft, cheese-like dead centre, typical of tuberculosis; non-caseating ones, as in sarcoidosis, have none.
Normal function
Macrophages that engulf, kill and report
Blood monocytes enter the tissues and become . They engulf microbes, dead cells and debris into a phagosome, which fuses with lysosomes whose acid, enzymes and reactive oxygen species kill and digest the contents.
Macrophages and dendritic cells also show fragments of what they have eaten to helper (CD4) T cells. The T cells answer with cytokines that make macrophages better killers. For most microbes and particles this clears the problem within days, and the macrophages leave or die quietly.
Underlying change · Step 1 of 5
An agent that macrophages cannot clear
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Underlying change · Step 2 of 5
Inside a granuloma
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 5
Immune or foreign-body; caseating or not
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 4 of 5
The classic specific infections
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
Containment, damage and escape
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .