Possible outcomes of acute inflammation

1. Possible outcomes of acute inflammation • Complete resolution • Little tissue damage • Capable of regeneration • Scarring (fibrosis) • In tissues unable to regenerate • organized into fibrous tissue • Abscess formation occurs with some bacterial or fungal infections • Progression to chronicinflammation

2. CHRONIC INFLAMMATION The processes of inflammation & healing (granulation tissue) proceed side by side

3. Chronic inflammationThe processes of inflammation & healing proceed side by side • Lymphocyte, macrophage, plasma cell (mononuclear cell) infiltration • Tissue destruction by inflammatory cells • Attempts at repair with fibrosis & angiogenesis (new vessel formation)

4. Chronic Inflammation • Long term (≥≥ days). • Characterized by the presence of macrophages, lymphocytes & plasma cells. • Accompanied by the proliferation of blood vessels & connective tissue (granulation tissue).

5. CHRONIC INFLAMMATION • may develop in the course of • Persistent / recurrent infection • or progressive acute inflammation • or low grade irritants that fail to elicit an acute response

6. Chronic inflammation • Persistent injury or infection (ulcer, TB) • Prolonged toxic agent exposure (silica) • Autoimmune disease states (RA, SLE)

7. Chronic InflammationThe Players • Macrophages process & deliver antigen to immunocompetent cells — mediate immune reactions. • Lymphocytes and plasma cells are involved in the immune reactions

8. The Players (mononuclear phagocyte system) • Macrophages • Scattered all over • Circulate as monocytes and reach site of injury within 24 – 48 hrs and transform • Become activated by T cell-derived cytokines, endotoxins, & other products of inflammation

9. The Players • T & B lymphocytes • Antigen-activated (via macrophages and dendritic cells) • Release macrophage-activating cytokines • in turn, macrophages release lymphocyte-activating cytokines • Plasma cells • Terminally differentiated B cells • Produce antibodies

10. The Players • Eosinophils • Found especially at sites of parasitic infection, or at allergic (IgE-mediated) sites

11. Types • NONSPECIFIC CHRONIC INFLAMAMTION- Diffuse accumulation of macrophages and lymphocytes at injury site Macrophages from 3 sources: 1) recruitment 2) local proliferation 3) prolonged survival

12. B. GRANULOMATOUS INFLAMMATION Granuloma formation –collection of modified macrophages Resemble squamous cells, therefore called “epithelioid” • surrounded by lymphocytes

13. Granulomatous Inflammation • Clusters of T cell-activated macrophages, which engulf and surround indigestible material (mycobacteria, foreign bodies) • Depostion of antigenic material, type IV hypersensitivity reaction

14. CD IFNg IL-12 TNFb IL-2 CD4+ Th1 cytokines IL-12 Proliferation Granuloma Formation IL-1, TNFa, IFNg, IL-12, GM-CSF, MIP-1a MF IL-8, IL-15, IL-16, RANTES TGF-b PDGF IGF-1 Fibrosis GRANULOMA FORMATION

15. In the usual hematoxylin and eosin–stained tissue sections, • the epithelioid cells have a pale pink granular cytoplasm with indistinct cell boundaries, often appearing to merge into one another. • The nucleus is oval or elongate and slipper/shoe/footprint shaped (folding of the nuclear membrane)

16. GRANULOMA

17. epithelioid cells fuse to form giant cells. • These giant cells may attain diameters of 40 to 50 μm. • containing 20 or more small nuclei arranged either peripherally (U /semicircle/garland/horse-shoe shape) - Langhans-type giant cell or haphazardly - foreign body–type giant cell

19. Foreign Body Reaction • Indicated by the presence of multinucleated foreign body giant cells and the components of granulation tissue (macrophages, fibroblasts, and capillaries) • The biomaterial will often determine the composition of the foreign body response

20. FOREIGN BODY GIANT CELL