This slide can cover all the mediators of chronic inflammation

1. CHRONIC
INFLAMMATION
DR SHAMS MWT

2. Chronic inflammation is a response of
prolonged duration (weeks and months)in
which inflammation, tissue injury, and
attempts at repair coexist, in varying
combinations
Delayed response but more specific

3. stimuli
 Persistent infection (most common)
Hypersensitivity reactions (allergic
and autoimmune diseases)
 Prolonged exposure to toxic
agent
(endogenous toxic agent example high level of lipid and
cholesterol deposit in the tissue cause atherosclerosis)
(exogenous toxic agent example particulate silica when
inhaled for prolonged period cause inflammatory lung
disorder called silicosis

4. Morphological features
 There will be macrophages, lymphocytes and
plasma at the site of chronic inflammation
 Tissue destruction caused by foreign
agent and inflammatory cells
 Healing process will also continuous to
replace damaged tissue

5. Cells and mediators of chronic inflammation
MACROPHAGE
 macrophage are 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.
 On the basis of location macrophage of liver (kupffer
cells),spleen and lymph nodes (histiocytes),skin (langerhans
cells) and lungs (alveolar macrophages) {reticuloendothelial
system}
 In inflammatory reaction the progenitors cells in the bone
marrow give rise to monocytes which enter the blood and
then migrate to various tissues and differentiate to
macrophages.

7. Role of macrophage
 Dominant cells in most inflammatory reaction ,which contribute to
the reaction by secreting cytokines and growth factors that act on
various cells, by destroying foreign invaders and tissues and by
activating other cells, nearby T lymphocytes.
 Professional phagocytic cells
Activation of macrophage
Classical macrophage activation;the stimuli for classical
activation of macrophage are microbial product and cytokine
IFN(gamma) which activate M1macrophage and produce NO and
ROS and lysosomal enzymes which has the ability to kill ingested
organism and produce IL1,IL6,IL12 and TNF(which further proceeds
the inflammation).

8. Alternative macrophage activation; is stimulated by IL4 and IL13
which activate M2 macrophage which produce IL10 and TGFß( have
antiinflammatory role and help to repair the tissue and initiate fibrosis).
Significance of macrophage;
 Initially macrophage secretes certain chemokines which help in the
initiation, propagation and repairing of inflammatory reaction.
 Act as antigen presenting cells to the T lymphocytes( which
activate T cells that produce certain chemicals and again activate
macrophages)

9. Role of T lymphocytes
 Produced in the bone marrow as progenitor T cells
 Further develop in the thymus and TCR undergoes
rearrangement
 Progenitor cells become CD4+ helper T cells or CD8+
cytotoxic T cells .
 TCR complex recognize antigens presented on MHC
 CD4+ T cells recognize MHC class2
 CD8+ T CELLS recognize MHC class1

10. CD4+ T cells activation
 Extra cellular antigen is phagocytosed, processed and
presented via MHC class2 (APCs)
 B7 on APC binds CD28 on CD4+ T cells providing 2nd
activation signals
 Activated CD4+ helper T cells secrete cytokines that help
inflammation

11. THREE SUBSETS OF CD4+ T CELLS
TH1 subset; secrete IL-2 ( T cell growth factor and CD8+ T cell
activator)
activate the classical pathway of macrophage by IFN(gamma)
TH2 subset ;
 secrete IL4 which helps the B cells ( class switching of IgG
to IgE
 IL5 ( chemotaxis of easinophil and activation, maturation of B
cells to plasma celld , and class switching to IgA
 IL10 which inhibit TH1 phenotype
 IL13 which activate alternative pathway of macrophage

12. TH17 subset;
 Secrete IL17 which induces secretion of chemokines
responsible for recruiting neutrophils into the reaction.
Both TH1 and TH17 subset are involved in defense
against bacteria , virus and autoimmune disease
While TH2 subset are involved in defense against
parasites and allergic inflammations.

20. THANK YOUs