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Inflammation (5 of 5)
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What will we discuss today?
• Chronic inflammation
• Granulomatous inflammation
• Systemic effects of inflammation
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Chronic inflammation…In general
• Days/weeks to years
• Conditions causing chronic inflammation: -Persistent infections…-TB (What is the microorganism?)
-Treponema pallidum (What does this microorganism cause?)
-Some viruses
-Some fungi
-Immune mediated hypersensitivity diseases…acute and chronic reactions… but in general:
chronic
-Prolonged exposure to toxic agents…mention 2 examples (one endogenous and one
exogenous)
-Diseases that chronic inflammation is one of their mechanisms…e.g, Alzheimer, DM type 2,
some cancers…etc
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Cells and mediators of chronic inflammation
• The major two types of cells:
These are the dominant here
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Macrophages
• Resident macrophages in tissues have special names:
-in liver: Kupffer cells
-in spleen and lymph nodes: sinus histiocytes
-CNS: microglial cells
-in lung: alveolar macrophages
• 24-48 hours of acute inflammation…they predominate after being recruited to the tissue (they were monocytes in blood)
• Longer life span and better phagocytosis than blood monocytes
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2 major pathways of macrophage activation:
Robbins basic pathology 9th edition…modified
From T lymphocytes and others And foreign materials
From -T lymphocytes -mast cells -eosinophils…etc.
The major role of alternatively activated macrophages
Including angiogenesis
Do not forget that macrophages also secrete TNF, IL-1, chemokines, eicosanoids…etc
Also induces macrophages to become multinucleated giant cells
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Macrophage
T lymphocyte
Antigen presentation and activation (IL-12…etc.)
Activation & recruitment
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Lymphocytes
• B cells…can develop into plasma cells…secrete immunoglobulins (antibodies)
• T cells: -Cytotoxic (CD8+)
-T helper (CD4+)
-Regulatory T cells These are especially important in chronic inflammation
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CD4+ helper T cells
• TH1 cells IFN-γ activates macrophages in the classical pathway
• TH2 cells IL-4, IL-5, and IL-13 -recruit and activate
eosinophils
-alternative pathway of
macrophage activation
• TH17 IL-17 recruitment of -neutrophils
-monocytes
Important in allergy and helminthic infections
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Other cells of chronic inflammation
• Eosinophils:
-parasitic infections
-allergy
…secrete major basic protein…special action against parasites, but also
injures tissues
• Mast cells:
-allergy…in cooperation with IgE release of histamine and eicosanoids
-secrete cytokines…TNF, chemokines…etc
• In some conditions…neutrophils are still activated and present in large numbers
= “Acute on chronic”
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Granulomatous inflammation
• A pattern of chronic inflammation
• Aggregates of activated macrophages + scattered lymphocytes
Robbins basic pathology 9th edition
This example is a caseating granuloma
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Granulomatous inflammation, cont’d
• Mechanisms:
-Persistent T cell responses to certain microbes chronic macrophage activation
-Some autoimmune mechanisms…example?
-Due to foreign bodies…= foreign body granulomas
-Sarcoidosis
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Systemic effects of inflammation
= acute phase reaction
*The most important here are:
-TNF
-IL-1
-IL-6
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Acute phase reaction, clinical & pathological changes
• Fever
…pyrogens synthesis of prostaglandins
…prostaglandins stimulate release of neurotransmitters
In vascular and perivascular cells of the hypothalamus
*Exogenous pyrogens (bacterial products, e.g., LPS) stimulate release of endogenous pyrogens (IL-1 & TNF)
eicosanoids (including prostaglandins)
Especially PGE2
They reset the temperature set point at higher level
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Acute phase reaction, clinical & pathological changes, cont’d • Elevated plasma levels of acute-phase proteins
-C-reactive protein (CRP)
-Fibrinogen
-Serum amyloid A (SAA) protein
**What is erythrocyte sedimentation rate (ESR)?
Synthesized by hepatocytes …especially due to IL-6
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Acute phase reaction, clinical & pathological changes, cont’d
• Leukocytosis…?
…What is “shift to the left”?
…What is leukemoid reaction?
…What is neutrophilia?
…What is eosinophilia?
…What is leukopenia?
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Acute phase reaction, clinical & pathological changes, cont’d
* heart rate & blood pressure
* sweating
*Chills and rigors…What are these?
*Anorexia
*Somnolence
*Malaise
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