Pathology of inflammation

1. Outcomes of acute
inflammation

3. Causes of Chronic inflammation
• Persistent infections
• Infections -- difficult to eradicate, e.g. mycobacteria and certain
viruses, fungi, and parasites
• unresolved acute inflammation
• Hypersensitivity diseases
• autoimmune diseases (rheumatoid arthritis)
• Allergic diseases
• Prolonged exposure to potentially toxic agents
Eg Silicosis, asbestosis
• Miscellaneous
Eg neurodegenerative diseases, atherosclerosis

4. LYMPHOCYTES PLASMA CELLS
MACROPHAGES
Cells Involved in Chronic inflammation

5. Characteristics of Chronic inflammation
•Infiltration by
mononuclear cells
(lymphocytes,plasma
cells, macrophages)
•Tissue destruction
•Healing – angiogenesis
& fibrosis

6. Microbial products
(endotoxin)
T cell–derived signals- IFN-γ
Foreign substances
• NO and ROS
• Lysosomal
enzymes
• Secrete
cytokines
T lymphocytes and
other cells
IL4,IL13
Tissue repair - growth
factors
angiogenesis, activate
fibroblasts, and stimulate
collagen synthesis

7. Classical & Alternative pathways of Macrophage
activation

8. CD4+ T lymphocytes
•Promote inflammation
•TH1 cells produce IFN-γ --Classical pathway of
macrophage activation
•TH2 cells secrete IL-4, IL-5, and IL-13 -- Alternative
pathway of macrophage activation.
•TH17 cells secrete IL-17 and other cytokines, -- secretion
of chemokines -- recruiting neutrophils (and monocytes)

9. GRANULOMATOUS
INFLAMMATION

10. Granulomatous inflammation
A form of chronic inflammation characterized
by the formation of granulomas.
Granulomas: Microscopic aggregation of
activated macrophages called epithelioid cells

11. • Granuloma = Nodular collection of activated macrophages
called epithelioid cells,surrounded by a rim of lymphocytes
• Epitheloid = resemble epithelial cells
Pale pink cytoplasm,
with indistinct cell
borders, merge into
one another
Oval/elongated
vesicular
nuclei,sometimes
folded nuclear
membrane
Epithelioid cells

12. Other components of granulomas
Giant cells : formed by the fusion of epithelioid cells : Large cells
have many nuclei : usually 20 or more nuclei
Lymphocytes : integral part as it is a type of chronic inflammation,
sometimes plasma cells
Fibrosis : tissue damage leads to fibrosis

13. Peripheral horse shoe
arrangement of nuclei
: randomly distributed nuclei
Foreign body type of giant cells
Langhans type of giant cells

14. Necrosis
Sometimes granulomas have
central necrosis : eg
Tuberculosis (soft
granulomas)
Sometimes granulomas do
not have necrotic centres (
hard granulomas) eg :
sarcoidosis, foreign body
granuloma etc

15. Lymphocytes
Epitheliod histiocytes
Multinucleated cell
Necrosis

16. Why does granulomatous inflammation occur
• Granulomas are encountered in response to specific
conditions
Phagocytes ordinarily remove agents that incite an acute
inflammatory response. However, there are circumstances in
which phagocytes cannot digest the substances

17. Causes and types
Foreign body granuloma
.
Foreign bodies are large enough to
preclude phagocytosis by a
macrophage eg Suture
Immune granuloma
are caused by insoluble
indigestible particles, eg some
microbes eg Mycobacteria:
hence cannot be phagocytosed
Induce cell-mediated immune
response-Type IV
hypersensitivity reaction

18. Antigen
Presentation
to T cells
Lymphocyte
Activated
Lymphocyte
IFN-
IL-1 TNF-
T cells
Activated
T cells
Activated
macrophages
(Epithelioid cells)
IL - 12
PATHOGENESIS
IL - 2

19. Mechanism of granulomatous inflammation

20. Granulomatous Inflammation : examples
Immune granuloma
 Bacteria
 Tuberculosis
 Leprosy
 Parasites
 Schistosomiasis
 Leishmaniasis
 Fungi
 Histoplasmosis
 Blastomycosis
 Unknown
 Sarcoidosis
Non-immune granuloma
 Foreign body
 Suture
 Graft material
 talc (associated with
intravenous drug abuse)

21. 1) The most important cell in granulomatous inflammation
2) A cytokine that is important in activating macrophages
and transforming them into epithelioid cells
3) Multinucleated cell in TB
4) Pathogenesis of immune type granulomatous
inflammation