Chronic and Granulomatous Inflammation

Acute vs. Chronic Inflammation

Histopathological differences, and differ in time course of the inflammatory response

Acute inflammation (typical of early phases of the inflammatory response) involves polymorphonuclear neutrophil leukocytes as the principal cellular effectors

Chronic inflammation (tends to occur over a longer time) involves mononuclear leukocytes (monocytes, macrophages, lymphocytes and plasma cells)

Acute inflam, chronic inflam, and repair follow one another in inflam lesions with no sharp boundaries in space or time

Situations Favoring Chronic Inflammation

Persistent Infection: Tuberculosis, Fungal Infections, Syphilis, Parasites (ie Chronic Bronchitis)

Prolonged Irritation: Foreign Body, Insoluble Endogenous Accumulations (ie Pericardial Poudrage)

Cellular Immune Response: Viral Infections, Graft Rejection, Certain Malignancies, Autoimmunity (ie Viral Pneumonia, Halo Nevus)

Defective Acute Inflammatory Response

Differences between Neutrophils and Macrophages

Neutrophils are terminally differentiated on arrival at the site of inflammation

Blood monocytes differentiate into macrophages, which undergo further activation in response to inflam stimuli

Neutrophils are incapable of cell division

Macrophages are mitotically active

Neutrophils execute a limited stereotypical mission: Margination, diapedesis, chemotaxis, phagocytosis, degranulation

Macrophages do the above, also mediate systemic effects: Fever, leukocytosis, acute phase response induction

Key Role of the Macrophage in Chronic Inflammation

External Stimuli (antigens, endotoxin, etc.) activate macrophages and lymphocytes

Activated Macrophage secretes monokines (IL-1, IL-6, TNF) and activates more lymphocytes via antigen presentation

Activated Lymphocyte secretes Lymphokines (IFN-g ) which activate more macrophages, and undergoes clonal expansion and Ab production

Overall: external stimuli Þ macrophage becomes activated Þ antigen presentation Þ lymphocyte becomes activated Þ lymphokines Þ macrophage becomes activated Þ repeats (snowball effect)

The Granuloma

Lymphocytes and macrophages accumulate in sites of chronic inflammation by 3 mechanisms: Chemotaxis, Arrested cell migration, Mitotic proliferation

In some instances, the chronic inflammatory response becomes a sharply circumscribed pale mass, called granuloma

Granulation Tissue and Granulocyte have nothing in common with Granulomas so do not confuse them!!

The Ideal Granuloma – well circumscribed, Epithelioid histiocytes (activated macrophages) near center, lymphocytes near edge