A topic of General Pathology made easy for third year and M.Phil. students.

1. CHRONIC INFLAMMATION
Dr. Sobia Khalid

2. DEFINITION
• Chronic inflammation is inflammation of
prolonged duration (weeks or months) in
which inflammation, tissue injury, and
attempts at repair coexist, in varying
combinations.

3. CAUSES OF CHRONIC INFLAMMATION

4. Persistent infections
• Mycobacteria
• Viruses
• Fungi
• parasites.
delayed-type hypersensitivity
granulomatous reaction

5. Immune-mediated inflammatory
diseases
• autoimmune diseases
• immune responses against microbes
• allergic diseases
Fibrosis may dominate the late stages.

6. Prolonged exposure to potentially
toxic agents, either exogenous or
endogenous.
• silicosis
• Atherosclerosis

7. MORPHOLOGIC FEATURES

8. • Infiltration with mononuclear cells
Macrophages
Lymphocytes
plasma cells

9. • Tissue destruction
persistent offending agent
inflammatory cells

10. • Healing by connective tissue replacement of
damaged tissue
proliferation of small blood vessels
(angiogenesis)
fibrosis

13. ROLE OF MACROPHAGES IN CHRONIC
INFLAMMATION

15. The roles of activated macrophages in chronic
inflammation

17. ROLE OF LYMPHOCYTES IN CHRONIC
INFLAMMATION

19. • Antigen-stimulated lymphocytes of different
types (T and B cells) use various adhesion
molecule pairs (selectins, integrins and their
ligands) and chemokines to migrate into
inflammatory sites.
• Cytokines from activated macrophages,
mainly TNF, IL-1, and chemokines, promote
leukocyte recruitment, setting the stage for
persistence of the inflammatory response.

20. • Lymphocytes and macrophages bidirectional
interactaction.

22. • Macrophages produce cytokines (notably IL-
12) that stimulate T-cell responses.
• Activated T lymphocytes produce cytokines,
some of which recruit monocytes from the
circulation and one, IFN-γ, is a powerful
activator of macrophages.
• immune inflammation

23. ROLE OF PLASMA CELLS IN CHRONIC
INFLAMMATION

25. • Plasma cells develop from activated B
lymphocytes.
• Produce antibodies directed either against
persistent foreign or self antigens in the
inflammatory site.

26. • In some strong chronic inflammatory
reactions, the accumulation of lymphocytes,
antigen-presenting cells, and plasma cells
may assume the morphologic features of
lymphoid organs, particularly lymph nodes,
even containing well-formed germinal
centers.
• These are called tertiary lymphoid organs.
Example.. rheumatoid arthritis.

27. ROLE OF EOSINOPHILS IN CHRONIC
INFLAMMATION

29. • Eosinophils are abundant in immune
reactions mediated by IgE and in parasitic
infections.
• A chemokine that is especially important for
eosinophil recruitment is eotaxin.

30. • Eosinophils have granules that contain major
basic protein, a highly cationic protein that is
toxic to parasites but also causes lysis of
mammalian epithelial cells.
• This is why eosinophils are of benefit in
controlling parasitic infections, but they
contribute to tissue damage in immune
reactions such as allergies.

31. ROLE OF MAST CELLS IN CHRONIC
INFLAMMATION

33. • Mast cells are widely distributed in
connective tissues.
• They participate in both acute and chronic
inflammatory reactions.
• Mast cells express on their surface the
receptor (FcεRI) that binds the Fc portion of
IgE antibody.

34. • In immediate hypersensitivity reactions, IgE
antibodies bound to the cells' Fc receptors
specifically recognize antigen, and the cells
degranulate and release mediators, such as
histamine and prostaglandins.

35. • Examples
allergic reactions to foods
insect venom
Drugs
sometimes with catastrophic results (e.g.
anaphylactic shock).

36. • Mast cells are also present in chronic
inflammatory reactions, and because they
secrete cytokines, they have the ability to
both promote and limit inflammatory
reactions in different situations.

37. 11.3.2015

38. GRANULOMATOUS INFLAMMATION

39. • A granuloma is a cellular attempt to contain
an offending agent that is difficult to
eradicate.
• In this attempt there is often strong
activation of T lymphocytes leading to
macrophage activation, which can cause
injury to normal tissues.

40. • Tuberculosis is the prototype of the
granulomatous diseases.
• Sarcoidosis
• Leprosy
• Brucellosis
• Syphilis
• Berylliosis
• reactions of irritant lipids
• some autoimmune diseases are also included.

41. Examples of Diseases with
Granulomatous Inflammation

43. DEFINITION
• A granuloma is a focus of chronic
inflammation consisting of a microscopic
aggregation of macrophages that are
transformed into epithelium-like cells,
surrounded by a collar of mononuclear
leukocytes, principally lymphocytes and
occasionally plasma cells.

45. GIANT CELL
• These giant cells may attain diameters of 40
to 50 μm. They have a large mass of
cytoplasm containing 20 or more small nuclei
arranged either peripherally (Langhans-type
giant cell) or haphazardly (foreign body–type
giant cell).

46. TYPES OF GRANULOMA

47. • There are two types of granulomas, which
differ in their pathogenesis.
Foreign body granulomas
Immune granulomas

48. Foreign body granulomas
• Foreign body granulomas are seen with
foreign bodies.
• Typically, foreign body granulomas form
around material such as talc (associated with
intravenous drug abuse), sutures, or other
fibers that are large enough to produce
phagocytosis by a single macrophage and do
not incite any specific inflammatory or
immune response.

49. • Epithelioid cells and giant cells are apposed
to the surface of the foreign body. The
foreign material can usually be identified in
the center of the granuloma, particularly if
viewed with polarized light, in which it
appears refractile.

51. Immune granulomas
• Immune granulomas are caused by a variety
of agents that are capable of inducing a cell-
mediated immune response.
• This type of immune response produces
granulomas usually when the inciting agent is
poorly degradable or particulate.

52. • In such responses macrophages engulf foreign
protein antigen, process it, and present peptides
to antigen-specific T lymphocytes, causing their
activation.
• The responding T cells produce cytokines, such
as IL-2, which activates other T cells,
perpetuating the response, and IFN-γ, which is
important in activating macrophages and
transforming them into epithelioid cells and
multinucleate giant cells.

53. • The prototype of the immune granuloma is
that caused by infection with Mycobacterium
tuberculosis. In this disease the granuloma is
referred to as a tubercle. It is often
characterized by the presence of central
caseous necrosis.
• In contrast, caseous necrosis is rare in other
granulomatous diseases.

54. • The morphologic patterns in the various
granulomatous diseases may be sufficiently
different to allow reasonably accurate
diagnosis by an experienced pathologist ;

55. • However, there are so many atypical
presentations that it is always necessary to
identify the specific etiologic agent by special
stains for organisms (e.g., acid-fast stains for
tubercle bacilli), by culture methods (e.g., in
tuberculosis and fungal diseases), by
molecular techniques (e.g., the polymerase
chain reaction in tuberculosis), and by
serologic studies (e.g., in syphilis).