granuloma

1. GRANULOMATOUS
INFLAMMATION

2. Introduction
• It is a distinctive pattern of
chronic inflammation
characterized by aggregates
of activated macrophages
that assume an epithelioid
appearance.
• Certain specific pathologic
states
• “Walls off”- offending agent
• Tuberculosis is the
prototype of a
granulomatous disease.

3. Granulomatous Disease
Disease Cause
Tuberculosis Mycobacterium tuberculosis
Leprosy Mycobacterium leprae
Syphilis Treponema pallidum
Cat Scratch Disease Gram (–) bacillus
Sarcoidosis Unknown etiology
Crohn’ Disease Immune reaction against intestinal
bacterial, self antigen

4. 1. Bacteria
Tuberculosis
Leprosy
2. Parasites
Schistosomiasis
3. Fungi
Histoplasmosis
Blastomycosis
4.Metal/Dust
Berylliosis
Silicosis
INFECTIOUS CAUSES

5. PATHOGENESIS OF GRANULOMA
Engulfment
by
Macrophages
• Unable to lyse eg. M. tubercle
• Undergo morphologic changes to epithelioid cells.
CD4+ T cells
• When macrophage fails to kill
• It presents it to CD4+ cells.
Cytokines
• IL-1 and IL-2, Interferon-γ, TNF-α
• Fibroblast proliferation

6. Histological features

7. Histological features
• The following three layer structure of the inflammatory
granulation tissue is common
• Resorption zone
– Innermost
– borders directly on the necrotic material and primarily consists
of phagocytic histiocytes.
– store the poorly soluble fat in lysosomal vacuoles - foam cells
• Granulation zone
– granulation tissue rich in capillaries and fibroblasts.
– Resorptive and reparative function
• Mature connective tissue zone
– oldest and outermost layer of tissue - highly fibrous connective
tissue

8. Centrally placed necrosis
Surrounded by epitheliod cells
An outer layer of lymphocytes
Plasma cells may be present
Few Giant cells present
Surrounded by fibrin and connective tissue
COMPONENTS OF
GRANULOMA

10. Histological features

11. COMPOSITION OF GRANULOMA
• Following structural
components
– Epitheloid cells
– Multinucleate giant
cells
– Lymphoid cells - cell
mediated immune
reaction
– Necrosis & Fibrosis.

12. Epithelioid cells
• epithelial cell-like appearance
• modified macrophages/histiocytes
• abundant cytoplasm with hazy outlines
• cell membrane of adjacent epithelioid cells is
closely apposed
• Epithelioid cells are weakly phagocytic

13. Multinucleate giant
cells
• fusion of adjacent epithelioid
cells
• 20 or more nuclei
• Langhans’ giant cells - nuclei
may be arranged
– Periphery
– Horseshoe
– Ring
– Clustered at the two poles.
• Foreign body giant cells –
centrally placed nuclei
• Weakly phagocytic

14. Multinucleate giant cells

15. Necrosis & Fibrosis
• Necrosis may be a
feature of some
granulomatous
conditions
– Central caseation
necrosis of tuberculosis
• Fibrosis - healing by
proliferating fibroblasts
at the periphery of
granuloma. Ex:
Rheumatoid Arthritis

16. Initial lesion of Leprosy

17. Pathogenesis
• No demonstrable toxins
• Virulence mycobacteria reach the
alveoli
• Macrophage – initiates
phagocytosis, but unable to do so
– bacterial sulfolipids inhibit the fusion
of phagocytic vesicles with
lysosomes
• multiply in the pulmonary
epithelium or macrophages
• 2 to 4 weeks - destroyed by the
immune system, but some survive
and are spread by the blood to
extrapulmonary sites
• Ability to survive and grow within
host cells

19. TUBERCULOSIS