Chronic inflammation

Professor. Amnia Diaz Chronic Inflammation

• Time course: – Greater than 48 hours (weeks, months, years) • Cell type – Mononuclear cells (Primarily , Lymphocytes, Plasma cells)

Chronic inflammation

• Chronic inflammation arises in various organs in 1 of 3 ways. – Following acute inflammation – After repeated bouts of acute inflammation (pneumonia) – Without prior acute inflammation (Tb, viruses, silica, asbestos, rheumatoid arthritis) Causes of Chronic inflammation • Persistent infections by microorganisms that are difficult to eradicate(e.g TB, Fungi) • Immune mediated inflammatory diseases(e.g Rheumatoid arthritis, Multiple sclerosis, Bronchial asthma) • Prolonged exposure to potentially toxic agents(e.g Exposure to silica-Silicosis, Atherosclerosis) Cells and mediators

• Histologically chronic inflammation includes: – Lymphocytes, plasma cells, and macrophages – Proliferation of fibroblasts and small vessels(granulation tissues) – Increased connective tissue – Tissue destruction Mononuclear (Macrophages/MOs/)

• The PMN is central to acute inflammation. • The is central to chronic inflammation – Synonyms: • Macrophages (MOs) • Histiocytes • Kuppfer cells (etc.) Macrophage origin:

• MOs come from the same cell line but differ depending on their microenvironment. They belong to the mononuclear system (RES). The RES system consists of the bone marrow, peripheral blood, and tissue. MO's share in common:

• Mobility --although slower than PMNs • Phago- and pinocytosis • Ability to become activated--especially by lymphokines, T cells, and anything that disturbs the cell membrane—and this allows more aggressive behavior in inflammation. • Ability to secrete large quantities of chemical mediators

MO functions

• Produce toxic, biologically active substances such as oxygen metabolites • Cause influx of other cells such as other macrophages and lymphocytes • Cause fibroblast proliferation and collagen deposition • MO time scale:

• MO’s begin emigration during acute inflammation and are the predominate cell type at 48 hours 3 ways in which MOs accumulate:

• Continued recruitment from the circulation--secondary to chemotactic factors • Division • Prolonged survival

Other cells in chronic inflammation: • Lymphocytes: Th1,Th2,Th17 • Plasma cells: • : • Mast cells • PMNs: Macrophage-lymphocyte interactions in chronic inflammation

Chronic Granulomatous Inflammation (GI)

• Definition:--a type or pattern of chronic inflammation defined by the presence of granulomas which are small, 0.5 to 2 mm collections of modified "epithelioid " histiocytes/macrophages and (Langhan's) giant cells (coalesced histiocytes), usually surrounded by a rim of lymphocytes. Giant cells

• Large multinucleate cells formed by the fusion of histiocytes. Types • Physiologic : - - • Pathologic: - Inflammatory - Foreign body - Langhans’ giant cell - Touton giant cell - Anitschkow cells(Aschoff body) - Tumoral - Reed Stemberg

Osteoclast Megakaryocytes

Foreign-body giant cell

• Is a collection of fused macrophages(giant cell) which are generated in response to the presence of a large foreign body. This is particularly evident with implants that cause the body chronic inflammation and foreign body response.

Langhans giant cells

• Are large cells found in granulomatous conditions. • They are formed by the fusion of epithelioid cells(macrophages), and contain nuclei arranged in a horseshoe-shaped pattern in the cell periphery. • Although traditionally their presence was associated with tuberculosis

Touton giant cells

• Are seen in lesions with high lipid content such as fat necrosis, , and xanthogranulomas. They are also found in dermatofibroma • They are formed by the fusion of epithelioid cells (macrophages), and contain a ring of nuclei surrounded by a foamy cytoplasm

Anitschkow cells

• Are cells associated with, and pathognomonic for, rheumatic heart disease. Anitschkow cells are enlarged macrophages found within granulomas (called Aschoff bodies) associated with the disease.

Tumor giant cell

Reed Sternberg cell

Granulomas occur in response to various diseases: • Foreign body • Tuberculosis (tb) • Fungal infections • Sarcoidosis • Schitosomiasis • Leprosy • Brucellosis • Syphilis

2 factors necessary for granuloma formation:

• Presence of indigestible organisms or particles (Tb, mineral oil, etc) • Cell mediated immunity (T cells)

Types of granulomas • Foreign body granuloma: Are incited by relatively inert foreign bodies(ex. Talc, Sutures) • Immune granuloma: are caused by a variety of agents that are capable of inducing a cell- mediated immune response, usually when the agent is poorly degradable or particulate (Ex Mycobacterium Tuberculosis) Special stain and methods for diagnosis • Acid fast stain for tubercle bacilli : TB and Fungal diseases by culture method. • Molecular techniques(polymerase chain reaction) in TB • Serologic studies: Syphilis

Outcome of chronic inflammation:

• Resolution/regeneration/restitution of normal structure • Repair/organization/healing by connective tissue/fibrosis/scarring • It can continue indefinitely--some disease processes are capable of continuing indefinitely such as rheumatoid arthritis.. Injury

Acute inflammation

Abscess Chronic inflammation

Resolution Repair Resolution

• Definition: Resolution is the return of tissue to its normal state. Factors necessary for resolution:

• Removal of the offending agent • Regenerative ability if cells have been destroyed • Intact stromal framework Stromal framework:

• It is not enough to be able to regenerate. There must be an adequate stromal framework. Injury

Acute inflammation

Abscess Chronic inflammation

Resolution Repair