1. CHRONIC INFLAMMATION

4. CHRONIC INFLAMMATION
Prolonged inflammatory response to persistent or recurrent stimulous.
Destruction and inflammation are proceeding at the same time along with an attempt at healing.

5. Causes of chronic inflammation
Persistent infections
Organisms usually of low toxicity that invoke delayed hypersensitivity reaction
M. tuberculosis and T. pallidum causes granulomatous reaction
Prolonged exposure to potentially toxic agents
Exogenous agents include silica which causes silicosis
Endogenous causes include atherosclerosis caused by toxic plasma lipid components

6. Autoimmunity
Auto-antigens provoke self-perpetuating immune responses that cause chronic inflammatory diseases like RA, MS
Responses against common environmental substances cause chronic allergic diseases, such as bronchial asthma

7. HISTOLOGICAL CHARACTERISTICS
Infiltration with mononuclear cells (eg. macrophages, lymphocytes and plasma cells) due to persistent reaction to injury
Tissue destruction induced by persistent agent or inflammatory cells
Attempts at healing by connective tissue replacement of damaged tissue with angiogenesis and fibrosis

8. Chronic inflammation
FIGURE 2–22A A, Chronic inflammation in the lung, showing all three characteristic histologic features: (1) collection of chronic inflammatory cells (*), (2) destruction of parenchyma (normal alveoli are replaced by spaces lined by cuboidal epithelium, arrowheads), and (3) replacement by connective tissue (fibrosis, arrows).

9. MORPHOLOGY
INFILTRATION
TISSUE DESTRUCTION
HEALING

10. CELLS IN CHRONIC INFLAMMATION

11. Cellular Players MACROPHAGES (aka, HISTIOCYTES) LYMPHOCYTES
PLASMA CELLS
EOSINOPHILS
MAST CELLS

12. MACROPHAGE
Derived from blood monocytes. Various levels of ‘activation’.
Functions:
Phagocytosis and destruction of debris & bacteria
Processing and presentation of antigen to immune system.
Control of other cells by cytokine release
Synthesis; not only cytokines, but also complement components, blood clotting factors, proteases, ....

13. Resident and activated macrophages
Kupffer cells - liver
Sinus Histiocytes - spleen and lymph nodes
Alveolar Macrophages – Lungs
Microglia – brain

17. LYMPHOCYTES Functions: Mainly immunological.
B lymphocytes differentiate to produce antibodies.
T lymphocytes involved in control & some cytotoxic functions.(recruit monocytes from the circulation with IFN-γ)

23. Other cells involved in chronic inflammation
Plasma cells:
Differentiated antibody-producing B lymphocytes. Implies considerable chronicity.
Eosinophils:
Allergic reactions, parasitic infestations, some tumours.
Fibroblasts / Myofibroblasts:
Recruited by macrophages; make collagen. See next lecture.

24. Eosinophils, Plasma cells, and Macrophages
This image is an area of inflammation showing eosinophils, plasma cells, and macrophages. Can you identify each of these cells? Use the feature box after attempting to find the cells. Under what conditions are eosinophils prominent in the inflammatory infiltrate?

26. CHRONIC INFLAMMATION
GRANULOMATOUS
CASEATING
NON CASEATING
NON SPECIFIC

27. CHRONIC NON-SPECIFIC (NON-GRANULOMATOUS) INFLAMMATION
It is the continuation of a partially successful acute inflammation & reaction to persistent extracellular bacteria
Histologically characterized by structureless unorganized diffuse infiltration of tissues by PMN’s and mononuclear cells

29. Granulomatous inflammation
Distinctive pattern of chronic inflammation. Cellular attempt to contain an offending agent that is difficult to eradicate (i.e. Tb)
Protective response to chronic infection or foreign material, preventing dissemination and restricting inflammation.
Persistent, low-grade antigenic stimulation
Hypersensitivity

30. A granuloma is a microscopic aggregation of macrophages that are transformed into epithelioid cells and giant cells surrounded by a collar of mononuclear leukocytes, principally lymphocytes and occasionally plasma cells

34. Causes of Granulomatous inflammation
INFECTIVE
Bacterial
Tuberculosis (Mycobacterium tuberculosis)
Leprosy (Mycobacterium leprae)
Syphilitic gumma (Treponema pallidum)
Parasitic
Schistosomiasis (Schistosoma mansoni, S. haematobium,
S. japonicum)

35. Fungal
Histoplasma capsulatum
Blastomycosis
Cryptococcus neoformans
Coccidiodes immitis
Inorganic Metals or Dusts
Silicosis
Berylliosis
Foreign Body
Suture, breast prosthesis, vascular graft
Unknown
Sarcoidosis

36. CELLS IN GRANULOMAS
*Macrophages are almost all recruited directly from the bloodstream monocytes.
*Epithelioid cells have abundant pink cytoplasm, indistinct borders, and elongated

37. The giant cells 40 to 50 µ in dia
abundant cytoplasm, multiple nuclei.
*Plasma cells produce antibodies against the persistent antigen or the altered tissue components.
*Lymphocytes are likely to be present even where there is no involvement of the immune system.

39. GIANT CELLS .
Multinucleate cells made by fusion of macrophages.

40. Langhans type giant cell - Tuberculosis

41. Foreign body type giant cells

43. TUBERCULOSIS Caused by M. tuberculosis. Acid Fast Bacillus
Produces no toxins or lytic enzymes
Causes disease by persistence and induction of cell-mediated immunity.
CHRONIC GRANULOMATOUS INFLAMMATION

44. Morphology
Caseating granuloma (tubercle): focus of activated macrophages (epithelioid cells), rimmed by fibroblasts, lymphocytes, histiocytes, occasional Langhans giant cells; central necrosis with amorphous granular debris; acid-fast bacilli

51. DIAGNOSIS Clinical features are not confirmatory.
Zeil Nielson Stain - 1x104/ml, 60% sensitivity
Release of acid-fast bacilli from cavities intermittent.
3 negative smears to assure low infectivity*
Culture most sensitive and specific test.
Conventional Lowenstein Jensen media 3-6 wks.
Automated techniques within 9-16 days
PCR is available, but should only be performed by experienced laboratories

54. Granuloma

55. Foreign body granuloma

56. NON CASEATING GRANULOMAS

57. Comparison of Acute and Chronic Inflammation
Process Acute Inflammation Chronic Inflammation
Initiators Microbial surfaces & fragments Non-digestable organisms
Injured tissue & tissue fragments Non-degradable foreign matter
Auto-immune reactions
Mediators Mast cell products (histamine) T-lymophocytes& macrophage Bradykinin products- cytokines and GF’s
Lysosomal components Proteases and reactive oxygen
Complement, lipid mediators Complement, lipid mediators
Vascular changes Vasodilatation & inc, permeability Minimal
Cell Neutrophils Monocytes/Macrophages
Populations Tissue macrophages Plasma cells, Fibroblasts
Time course Acute onset, minutes days Insidious onset, weeks  years
Outcome Resolution, Abscess formation Resolution, Tissue destruction,
Chronic inflammation fibrosis