1. Inflammation (5 of 5) Ali Al Khader, M.D. Faculty of Medicine
Al-Balqa’ Applied University

2. What will we discuss today?
Chronic inflammation
Granulomatous inflammation
Systemic effects of inflammation

3. 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

4. Cells and mediators of chronic inflammation
The major two types of cells:
These are the dominant here

5. 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

6. 2 major pathways of macrophage activation:
From T lymphocytes and others
And foreign materials
Also induces macrophages to become multinucleated giant cells
Do not forget that macrophages also secrete TNF, IL-1, chemokines, eicosanoids…etc
From -T lymphocytes
-mast cells
-eosinophils…etc.
The major role of alternatively activated macrophages
Robbins basic pathology 9th edition…modified
Including angiogenesis

7. Activation & recruitment
Macrophage
Activation & recruitment
Antigen presentation and activation (IL-12…etc.)
T lymphocyte

8. 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

9. CD4+ helper T cells
TH1 cells IFN-γ activates macrophages in the classical pathway
TH2 cells IL-4, IL-5, and IL recruit and activate
eosinophils
-alternative pathway of
macrophage activation
TH IL recruitment of -neutrophils
-monocytes
Important in allergy and helminthic infections

10. 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”

11. Granulomatous inflammation
A pattern of chronic inflammation
Aggregates of activated macrophages + scattered lymphocytes
This example is a caseating granuloma
Robbins basic pathology 9th edition

12. 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

13. Systemic effects of inflammation
= acute phase reaction *The most important here are: -TNF -IL-1 -IL-6

14. Acute phase reaction, clinical & pathological changes
Fever
…pyrogens synthesis of prostaglandins
…prostaglandins stimulate release of neurotransmitters
In vascular and perivascular cells of the hypothalamus
Especially PGE2
*Exogenous pyrogens (bacterial products, e.g., LPS) stimulate release of endogenous pyrogens (IL-1 & TNF)
eicosanoids (including prostaglandins)
They reset the temperature set point at higher level

15. 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

16. 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?

17. Acute phase reaction, clinical & pathological changes, cont’d
* heart rate & blood pressure * sweating *Chills and rigors…What are these? *Anorexia *Somnolence *Malaise

18. Thank You