Mediators of Chronic

Inflammation

Dr. Shreepriya Khurana

Dept of Prosthodontics and Crown & Bridge
 • Introduction
• Macrophages

Specific •
•
Lymphocytes
Other cells in Chronic Inflammation
Learning • Chronic Inflammatory Odontogenic
Cyst
Objectives • Conclusion
• References
 Tissue
Damage
Leukocyte
Fibrosis
Infiltration
Introduction
Chronic
Inflammation
Macrophages
Tissue cells derived from
hematopoietic stem cells in the
bone marrow and from
progenitors in the embryonic yolk
sac and fetal liver during early
development
• Dominant cells in most chronic inflammatory
reactions
• Circulating cells – Monocytes
• Diffusely scattered in most connective tissues

Liver- Kupffer cells

Spleen and lymph node- Sinus histiocytes
Central nervous system- Microglial Cells
Lungs- Alveolar macrophages

• Together form the mononuclear phagocyte

system
 Classical
Pathways of
Macrophage Activation
Alternative
Classical Macrophage Activation

Induced by microbial
Classically activated
products that engage Upregulate lysosomal
macrophages (M1)
TLRs by T cell derived enzymes
produce NO and ROS
signals (INF Gamma)

Enhanced ability to
kill ingested Stimulation of
organisms + cytokine inflammation
secretion
 • Induced by cytokines other than
Interferon gamma e.g IL-4 and IL-13
produced by T Lymphocyes
• Alternatively activated
Alternative macrophages(M2) principally help in
tissue repair
Macrophage
Activation • They secrete-
 Growth factors promoting angiogenesis
 Activate fibroblasts
 Stimulate collagen synthesis
• Ingest and eliminate microbes and dead tissues
• Initiate tissue repair and are involves in scar
formation and fibrosis
• Secrete inflammatory mediators like cytokines
(TNF, IL-1, chemokines etc) and eicosanoids
Functions of
• Display antigens to T lymphocytes and respond Macrophages
to signals from T cells, which sets up a
feedback loop that is essential for defence
against microbes in cell mediated immunity
Lymphocytes
• Microbes and other environmental
antigens activate T and B
lymphocytes, which amplify and
propagate chronic inflammation
Activated lymphocytes cause the inflammation
to be persistent and severe.

Dominant in chronic inflammation in

autoimmune and other hypersensitivity diseases

Antigen stimulated T and B-lymphocytes use

various adhesion molecule pairs and chemokines
to migrate to inflammatory sites
CD4+ T Lymphocytes

TH1 TH2 TH17

INF- Gamma IL-4, IL-5, IL-13 IL-17

Activates Recruit and Induce chemokine

macrophage by activate secretion
classical pathway eosinophils responsible for
recruiting
neutrophil into
Alternative reaction
pathway of
macrophage
activation
Other cells in
Chronic
Inflammation
Eosinophils Mast Cells Neutrophils
Abundant in IgE mediated
immune reactions and
parasitic infections Both acute and chronic Characteristic of acute
inflammatory reactions inflammation

Recruitment is driven by
adhesion molecules and
specific chemokines
Secrete a plethora of Can be induced by
Contribute in tissue cytokines that promotes activated macrophages
damage in immune inflammatory reaction and T lymphocytes
reactions such as allergies
 Apical Periodontal Cyst/ Radicular cyst

Inflammatory
Toxins exit apex of stimulus causes Lymphokine
T call activation
tooth epithelial production
proliferation

Proliferation and
Act on Rest of
altered Cyst formation
Malassez
differentiation
• Universal occurrence of an inflammatory
infiltration

Made up of-
• Lymphocytes and plasma cells Histology
• Polymorphonuclear lymphocytes
• Foamy Macrophages
 • Chronic inflammation is a
prolonged host response caused
by microbes or toxic substances
• The cellular infiltrate consists of
macrophages, plasma cells,

Summary lymphocytes and other leukocytes

• It is mediated by cytokines
produced by macrophages and
lymphocytes
• Bidirectional interactions between
these cells tend to amplify and
prolong the inflammatory reaction
 • Robbins & Cotran-
Pathologic basis of Diseases
(South Asian Edition)-
Volume I
References • Shafer, Hine, Levy- Shafer’s
Textbook of Oral Pathology
(8th Edition)
Thank You