Classification of chronic inflammation:

Chronic inflammation can be classified into the following two types based on histologic features: 

 1) Nonspecific chronic inflammation: This involves a diffuse accumulation of macrophages and lymphocytes at site of injury that is usually productive with new fibrous tissue formations. E.g. Chronic cholecystitis.

2) Specific inflammation (granulomatous inflammation):

Definition: Granulomatous inflammation is characterized by the presence of granuloma. A granuloma is a microscopic aggregate of epithelioid cells. Epithelioid cell is an activated macrophage, with a modified epithelial cell-like appearance (hence the name epithelioid). The epitheloid cells can fuse with each other & form multinucleated giant cells. So, even though, a granuloma is basically a collection of epithelioid cells, it also usually contains multinucleated giant cell & is usually surrounded by a cuff of lymphocytes and occasional plasma cells. There are two types of giant cells: 

a.  Foreign body-type giant cells which have irregularly scattered nuclei in presence of indigestible materials.

b.  Langhans giant cells in which the nuclei are arranged peripherally in a horse -shoe pattern which is seen typically in tuberculosis, sarcoidosis etc… 

Giant cells are formed by fusion of macrophages perhaps by a concerted attempt of two or more cells to engulf a single particle.

Pathogenesis:

 There are two types of granulomas, which differ in their pathogenesis.

A. Foreign body granuloma 

These granulomas are initiated by inert foreign bodies such as talc, sutures (non-absorbable), fibers, etc… that are large enough to preclude phagocytosis by a single macrophage and do not incite an immune response. 

B. Immune granulomas

Antigen presenting cells (macrophages) engulf a poorly soluble inciting agent. Then, the macrophage processes and presents part of the antigen (in association with MHC type2 molecules) to CD4+T helper 1 cells which become activated. The activated CD4+ T-cells produce cytokines (IL-2 and interferon gamma).The IL-2 activates other CD4+T helper cells and perpetuates the response while IFN-γ is important in transforming macrophages into epitheloid cells and multinucleated giant cells. The cytokines have been implicated not only in the formation but also in the maintenance of granuloma.

Macrophage inhibitory factor helps to localize activated macrophages and epitheloid cells.

Diagram

Causes:

 Major causes of granulomatious inflammation include:

 a)  Bacterial: Tuberculosis, Leprosy, Syphilis, Cat scratch disease, Yersiniosis 

b)  Fungal: Histoplasmosis, Cryptococcosis, Coccidioidomycosis, Blastomycosis 

c)  Helminthic: Schistosomiasis 

d)  Protozoal: Leishmaniasis, Toxoplasmosis 

e)  Chlamydia: Lymphogranuloma venerum 

f)  Inorganic material:  Berrylliosis 

g)  Idiopathic: Acidosis, Cohn’s disease, Primary biliary cirrhosis 

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.