3. OBJECTIVES AND KEY PRINCIPLES TO BE
TAUGHT:
Upon completion of these 2 lectures , the student
should:
• Define chronic inflammation
• Describe the characteristic features of chronic inflammation.
• Describe the mechanism of chronic inflammation.
• Enumerate the cells of chronic inflammation.
• Enumerate the biologically active products secreted by
activated macrophage
• Define granulomatous inflammation
4. Chronic inflammation
• Definition :
• Inflammation of prolonged duration in which
active inflammation, tissue injury and the healing
proceed simultaneously
• It is slow evolving (weeks to months) resulting
into fibrosis
• It occurs in two major patterns :
• 1-chronic non specific
• 2-specific granulomatous inflammation
5. Causes of chronic inflammation
• Persistent infections
– Organisms usually of low toxicity that invoke delayed hypersensitivity
reaction
– Mycobacterium tuberculosis and Treponema 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
• Autoimmunity
– Auto-antigens provoke self-perpetuating immune responses that cause
chronic inflammatory diseases like Rheumatoid Arthritis, Multiple
Sclerosis.
– Responses against common environmental substances cause chronic
allergic diseases, such as bronchial asthma
6. MORPHOLOGIC FEATURES OF CHRONIC
INFLAMMATION
• Infiltration with mononuclear cells include
– Macrophages
– Lymphocytes
– Plasma cells
– and Eosinophils may be present also
• Tissue destruction and distortion
– induced largely by inflammatory cells.
• Healing (fibrosis)
– by connective tissue replacement of damaged
tissue, accomplished by proliferation of small
blood vessels (angiogenesis) and, in particular,
fibrosis (granulation tissue)
7. MONONUCLEAR CELL INFILTRATION
Macrophages
the dominant cellular player in chronic
inflammation
The mononuclear phagocyte system
(sometimes called reticuloendothelial
system) consists of closely related cells of
bone marrow origin, including blood
monocytes and tissue macrophages
MORPHOLOGIC FEATURES OF CHRONIC
INFLAMMATION
8. mononuclear phagocyte system
–monocytes begin to emigrate into extravascular tissues quite early in acute
inflammation and within 48 hours they may constitute the predominant cell type
9. Macrophages may be activated by a variety of stimuli,
including
cytokines (e.g., IFN-γ) secreted by sensitized T lymphocytes and
by NK cells
bacterial endotoxins
other chemical mediators
Activation results in
increased cell size
increased levels of lysosomal enzymes
more active metabolism
greater ability to phagocytos and kill ingested microbes.
Activated macrophages secrete a wide variety of
biologically active products that, if unchecked, result in
the tissue injury and fibrosis
MONONUCLEAR CELL INFILTRATION
Macrophages
10. .
Products of macrophages
1.Acid and neutral proteases
2.Chemotactic factors
3.Reactive oxygen metabolites
4.Complement components
5. Coagulation factors
6.Growth promoting factors for fibroblasts, blood
vessels and myeloid progenitor cells
7.Cytokines : IL-1, TNF
8.Other biologic active agents ( PAF, interferon, AA
metabolites)
to eliminate injurious agents such as
microbes
to initiate the process of repair
It is responsible for much of the tissue
injury in chronic inflammation
Function?!!..
11. The roles of activated macrophages in chronic inflammation.
Acute
&
Chronic inflam. persist
12. • In chronic inflammation, macrophage accumulation
persists, this is mediated by different mechanisms:
1. Recruitment of monocytes from the circulation, which results
from the expression of adhesion molecules and chemotactic
factors
2. Local proliferation of macrophages after their emigration from
the bloodstream
3. Immobilization of macrophages within the site of inflammation
Macrophages
13.
14. • Lymphocytes
– Both T & B Lymphocytes migrates into
inflammation site
OTHER CELLS IN CHRONIC INFLAMMATION
15. Activated lymphocytes and macrophages influence each other and also release
inflammatory mediators that affect other cells.
–Lymphocytes and macrophages interact in a bidirectional way, and these
reactions play an important role in chronic inflammation
16. •Eosinophils
are abundant in immune reactions mediated by IgE and in parasitic
infections
• respond to chemotactic agents derived largely from mast cells
• Granules contain major basic protein: toxic to parasites and lead to
lysis of mammalian epithelial cells
17. Morphological Features of
Chronic Inflammation
II - Tissue destruction
Occur due to:
• Inflammatory cells.
• Persistent infecting material.
18. Morphological Features of
Chronic Inflammation
III - Removal of damaged tissue, (healing):
• Occur by proliferation of small blood vessels,
(angiogenesis).
• Proliferation of fibroblast, (fibrosis-repair).
26. Granulomatous Inflammation
• Diffinition: A distinctive pattern of chronic
inflammation characterised by; Aggregations
of macrophages having an enlarged,
squamous cell-like appearance (called
epithelioid macrophages)
• Granuloma = Nodular collection of epithelioid
macrophages surrounded by a rim of
lymphocytes
27. Granulomatous inflammation
Granulomas are millimeter size nodules of
chronic inflammatory cells that can be isolated
or confluent.
Granuloma formation is the result of dealing
with indigestible substances or pathogens
and walls them off
The essential component are modified
macrophages named epithelioid cell (because
of shape).
Epithelioid cells can form multinucleated giant
cells.
Epithelioid cells are surrounded by a collar of
lymphocytes and occasionally plasma cells.
Fibrous connective tissue often surrounds
granulomas (remodeling of tissue)
Areas within the granuloma can undergo
necrosis (prototype: caseous necrosis in
tuberculosis). calcification or liquefaction
and formation of a cavern if drained.
35. Continuous assessment
• In the site of chronic inflammation, which of
the following component
is LEAST likely to be seen?
• A) Macrophages
• B) Neutrophils
• C) Plasma cells
• D) Lymphocytes
36. Continuous assessment
• Which is a good example of granulomatous
inflammation ?
• A) Abscess.
• B) Tuberculosis .
• C) Ulcer.
• D) fistula .
