Transcript Chronic Inflammation

CHRONIC
INFLAMMATION
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.
•
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
•
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
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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
MORPHOLOGY
• INFILTRATION
• TISSUE DESTRUCTION
• HEALING
Cellular Players
• MACROPHAGES (aka,
HISTIOCYTES)
• LYMPHOCYTES
• PLASMA CELLS
• EOSINOPHILS
• MAST CELLS
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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, ....
Resident and activated
macrophages
• Kupffer cells - liver
• Sinus Histiocytes - spleen and lymph
nodes
• Alveolar Macrophages – Lungs
• Microglia – brain
• 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)
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.
CHRONIC
INFLAMMATION
GRANULOMATOUS
CASEATING
NON SPECIFIC
NON CASEATING
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It is the continuation of a partially successful
acute inflammation & reaction to persistent
extracellular bacteria
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Histologically characterized by structureless
unorganized diffuse infiltration of tissues by
PMN’s and mononuclear cells
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
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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
Causes of Granulomatous
inflammation
INFECTIVE
Bacterial
Tuberculosis (Mycobacterium tuberculosis)
Leprosy (Mycobacterium leprae)
Syphilitic gumma (Treponema pallidum)
Parasitic
Schistosomiasis (Schistosoma mansoni, S.
haematobium,
S. japonicum)
Fungal
Histoplasma capsulatum
Blastomycosis
Cryptococcus neoformans
Coccidiodes immitis
Inorganic Metals or Dusts
Silicosis
Berylliosis
Foreign Body
Suture, breast prosthesis, vascular graft
Unknown
Sarcoidosis
*Macrophages are almost all recruited directly from
the bloodstream monocytes.
*Epithelioid cells have abundant pink cytoplasm,
indistinct borders, and elongated
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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.
• .
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Multinucleate cells made by fusion of
macrophages.
TUBERCULOSIS
•Caused by M. tuberculosis.
•Acid Fast Bacillus
•Produces no toxins or lytic enzymes
•Causes disease by persistence and
induction of cell-mediated immunity.
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CHRONIC GRANULOMATOUS
INFLAMMATION
Morphology
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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
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.
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◦ Conventional Lowenstein Jensen media 3-6 wks.
◦ Automated techniques within 9-16 days
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PCR is available, but should only be
performed by experienced laboratories
Granuloma
Foreign body granuloma
NON CASEATING GRANULOMAS
Comparison of Acute and Chronic Inflammation
Process
Acute Inflammation
Chronic Inflammation
Initiators
Microbial surfaces & fragments
Injured tissue & tissue fragments
Mediators
Mast cell products (histamine)
Bradykinin
Lysosomal components
Complement, lipid mediators
Non-digestable organisms
Non-degradable foreign matter
Auto-immune reactions
T-lymophocytes& macrophage
products- cytokines and GF’s
Proteases and reactive oxygen
Complement, lipid mediators
Vascular changes Vasodilatation & inc, permeability
Minimal
Cell
Populations
Neutrophils
Tissue macrophages
Monocytes/Macrophages
Plasma cells, Fibroblasts
Time course
years
Acute onset, minutes days
Insidious onset, weeks 
Outcome
Resolution, Abscess formation
Chronic inflammation
Resolution, Tissue destruction,
fibrosis
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