This document discusses inflammation and chronic inflammation. It defines inflammation as the body's protective response to remove injuries, necrotic cells, and stimulate healing. Chronic inflammation is inflammation that lasts weeks to years, with simultaneous active inflammation, tissue injury, and healing. The key cellular players in chronic inflammation are macrophages and lymphocytes, which attempt to eliminate pathogens but can also cause tissue damage. Chronic inflammation can result from persistent infections, autoimmune diseases, or prolonged exposure to toxins.

1. Lecture 11 Inflammation

2. Definition:
Inflammation is a protective response intended to
remove injuries stimuli as well as the necrotic
cells and tissues resulting from original insert.
OR
Repair process that causes the replacement of
damaged tissues by regeneration of
parenchyma cells or by filling of any residual
defect by fibrous scar tissues.
Inflammation:

3. ADVANTAGES:
• It causes destruction of microbes.
• Causes detoxification of toxins.
• Clears infections.
• Helps in healing process.
• Causes repair of damaged tissues.

4. DISADVANTAGES:
Inflammatory responses are sometimes harmful
as they cause:
• Life threatening anaphylactic reactions to insects
bites, drugs and other chronic diseases like
Rheumatoid arthritis, Atherosclerosis etc.
• Inflammation of peritoneum leads to fibrous bands
that causes obstruction of intestines.
• Pericardial inflammation causes the formation of
dense pericardium that impairs cardiac functions.

6. PLAYERS OF INFLAMMATION:
The inflammatory responses have many players.
They include:
1) CIRCULATING CELLS:
I. Bone marrow derived polymorph nuclear
leukocytes e.g., Basophils, Esinophils and
Neutrophils.
II. Lymphocytes
III. Monocytes
IV. Platelets.
2) CIRCULATING PROTEINS:
I. Clotting factors
II. Complement proteins

7. 3) VASCULAR WALL CELLS:
I. Connective tissue cells
II. Smooth muscle cells
III. Epithelial cells
4) EXTRA CELLULAR MATRIX:
I. Fibrous structural proteins e.g., Elastin &
Fibrinogen
II. Gel-forming proteoglycans

8. Inflammatory stimulus Chemical mediators
Inflammatory response until
injuries stimulus is removed
When the inflammatory stimulus is removed these
mediators are then dissipated, catabolized or
removed.
TYPES OF INFLAMMATION:
• Acute inflammation
• Chronic inflammation
PROCESS OF
INFLAMMATION:

9. Chronic inflammation is the inflammation with
prolonged duration usually from weeks to months
and sometimes to years in which active
inflammation, tissue injury and healing process
proceed simultaneously.
DISTINGUISHING FEATURES:
• Infiltration of mono-nuclear cells like
lymphocytes, macrophages and plasma cells.
• Destruction of tissue by inflammatory cells.
• Proliferation of new vessels leading to repair
(angiogenesis & fibrosis).
CHRONIC INFLAMMATION:

10. ORIGIN AND PROCESS:
Chronic inflammation arises from acute inflammation. This
transition takes place if the acute responses cannot be
resolved either because of the persistence e.g., of injuries
stimuli or by interference of the normal healing process e.g.,
peptic ulcer.
Some types of injuries engender responses with chronic
inflammation initially e.g., viral infections.
SETTINGS LEADING TO CHRONIC INFLAMMATION:
I. Viral infections
II. Persistent microbial infections
III. Prolonged exposure to potentially toxic materials
IV. Autoimmune diseases

11. The dominant cellular player in chronic inflammation is the tissue macrophage
It is joined by lymphocytes and plasma cells,
however mast cells and eosinophils are as well involved in
chronic allergic diseases
Blood monocytes Tissue macrophage (RES)
migrate into tissue
within 48 hours
after injury
and differentiate
Lymphocyte Plasma cell

12. CHRONIC INFLAMMATORY CELLS & MEDIATORS:
1) MACROPHAGES:
Macrophages are white blood cells within tissues, produced
by the division of monocytes.
A majority of macrophages are stationed at strategic points
where microbial invasion or accumulation of dust is likely
to occur. Each type of macrophage, determined by its
location, has a specific name:
• In liver Kupffer cells
• Spleen and lymph nodes Sinus histocytes
• Nervous system Microglial cells
• Lungs Alveolar
macrophages

13. IFN-g
Activated T cell or NK cell
Tissue macrophage
Activated macrophage
Non Immune activation:
Endotoxins,
fibronectin,
chemical mediators
Tissue injury
Toxic oxygen metabolites
Metallo-proteases
Coagulation factors
AA metabolites and NO
Fibrosis (Scaring)
Growth factors involved
in fibroblast proliferation
(PDGF,TGFb,FGF)
Angiogenesis factors
(FGF,VEGF)
Collagen deposition
(IL-13 and TGFb)
During chronic inflammation macrophages serve to eliminate
injuriess agents and initiate repair- however, they are as well
responsible for much of the tissue injury that occurs

14. FUNCTIONS OF MACROPHAGES:
They help to:
• Filter the particulate matter
• Kill microbes
• Alert immune system of the body.
• Their life is 1-2 days.
ACTIVATION OF MACROPHAGES:
Activation of macrophages means:
• Increase in size
• Increase in lysosomal content
• Increase in metabolism
• Increase in microbial killing activity

15. ACTIVATION SIGNALS:
Different signals required to activate macrophages are:
• Cytokines produced by T-lymphocytes
• Bacterial endotoxins
• Different mediators produced during acute
inflammation
• Extra cellular matrix proteins e.g., Fibrinogen
When macrophages become activated they produce
different type of biologically active substances that
either cause ;
Cell injury
OR
Fibrosis.

16. Cell injury causing substances:
• Acid and neutral proteases
• Complement proteins C1 to C5
• Coagulating factors V & VШ
• Amino acids metabolites
• Cytokines
• Tumor necrosis factor
Fibrosis causing substances:
• Growth factors
• Fibrogenic cytokines
• Angiogenesis factors
• Regeneration and remodeling factors

17. TYPES OF CHRONIC INFLAMMATION:
1) AGRANULOMATOUS:
Granuloma is not formed,
Inflammation is characterized by all features of chronic
inflammation.
Examples:
• Chronic viral infections e.g., Hepatitis
• Chronic autoimmune diseases e.g., Rheumatoid
arthritis and Ulcerative colitis
• Chronic chemical intoxication e.g., Chronic
alcoholic liver disease
• Allergic reactions e.g., Bronchial asthma

18. 2) GRANULOMATOUS INFLAMMATION:
Characterized by aggregates of activated macrophages
that assume a squamous cell like epithelloid
appearance.
GRANULOMA is defined as aggregates of
macrophages formed due to persistant response of T-
lymphocytes to particular antigens.
This has a granular cheesy appearance called as caseous
necrosis.
Examples are:
Bacterial:
Tuberculosis , Leprosy, Syphilis gumma etc.

19. Thank you for listening
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