This document summarizes the key aspects of inflammation. It begins by defining inflammation and describing the cardinal signs. It then discusses the etiological factors, types of inflammation (acute vs chronic), and the haemodynamic and cellular events in acute inflammation. Specifically, it outlines the vascular changes, increased permeability, exudation of leukocytes, and process of phagocytosis. It also discusses the chemical mediators of inflammation like histamine, kinins, cytokines, prostaglandins, and the resolution of inflammation. Finally, it concludes that inflammation is an important immune response but better understanding its pathways could aid in treating diseases.

1. PRESENTED BY : Dr. HARDI GANDHI
GUIDED BY : Dr. NEERAJ DESHPANDE

2. INTRODUCTION
 Inflammation is defined as the local response of living
mammalian tissues to injury due to any agent.
 Body defense reaction – eliminate or limit the spread of
injurious agent.

3. ETIOLOGICAL FACTORS:
 Infective agents like bacteria, viruses and their toxins, fungi,
parasites.
 Immunological agents like cell-mediated and antigen-
antibody reactions.
 Physical agents like heat, cold, radiation, mechanical trauma.
 Chemical agents like organic and inorganic poisons.
 Inert materials such as foreign bodies

4. CARDINAL SIGNS OF INFLAMMATION
 Rubor
 Tumor
 Calor
 Dolor
 Functio Laesa

5. TYPES OF INFLAMMATION
• Short Duration.
• Lasts less than 2 weeks.
• Represents early body reactions.
• Resolves Quickly.
ACUTE
• Longer duration.
• Either after causative agent of acute
inflammation.
• Or stimulus that induce chronic
inflammation from beginning.
(CHRONIC ACTIVE)
CHRONIC

6. • HAEMODYNAMIC CHANGES.
• ALTERED VASCULAR
PERMEABLITY
VASCULAR
EVENTS
• EXUDATION OF LEUKOCYTES
• PHAGOCYTOSIS
CELLULAR
EVENTS
ACUTE INFLAMMATION

7. A. HAEMODYNAMIC CHANGES
 Transient vasoconstriction : Immediate
vascular response irrespective of the type
of injury. Mainly by arterioles.
Mild injury - 3-5 seconds & Severe injury 3-5
minutes.
 Persistent progressive vasodilatation :
Mainly arterioles, others to a lesser
extent.
– obvious within half an hour of injury
– increased blood volume in microvascular
bed of the area
– redness and warmth

8.  Progressive vasodilatation
elevate the local hydrostatic pressure
– transudation of fluid into the extracellular space –
swelling
 Slowing or stasis
increased concentration of red cells, and thus, raised
blood viscosity
 Leucocytic Margination
- peripheral orientation of leucocytes (mainly
neutrophils) along the vascular endothelium
- stick to the vascular endothelium briefly
- move and migrate through the gaps between the
endothelial cells - extravascular space
- This is known is emigration.

9. ALTERED VASCULAR PERMEABILITY
 Accumulation of oedema fluid in interstitial compartment which
comes from blood plasma by its escape through the endothelial
wall of peripheral vascular bed.
 Escape of fluid is due to vasodilatation and consequent
elevation in hydrostatic pressure - transudate.
 Subsequently, the characteristic inflammatory oedema, appears
by increased vascular permeability of microcirculation –
exudate.

11. MECHANISMS OF INCREASED VASCULAR PERMEABILITY
 Contraction of endothelial cells.
 Retraction of endothelial cells
 Direct injury to endothelial cells
 Endothelial injury mediated by leucocytes
 Leakiness and neo-vascularization

12. Contraction of endothelial cells
 Affects venules exclusively.
 Endothelial cells develop
temporary gaps
 Contraction resulting in
vascular leakiness.
 Mediated by the release of
histamine, bradykinin and
other chemical mediators.
 Short duration (15-30
minutes) - immediately after
injury

13. Retraction of endothelial cells
 Structural re-organization
of the cytoskeleton of
endothelial cells -
Reversible retraction at the
intercellular junctions.
 Mediated by cytokines
such as Interleukin-1 (IL-1)
and Tumor necrosis factor
(TNF)-α

14. Direct injury to endothelial cells
 Causes cell necrosis and appearance of
physical gaps.
 Process of thrombosis is initiated at the
site of damaged endothelial cells.
 Affects all levels of microvasculature.
 Either appear immediately after injury and
last for several hours or days – severe
bacterial infections
 Or delay of 2-12 hours and last for hours or
days - moderate thermal injury and
radiation injury

15. Endothelial injury mediated by leucocytes
 Adherence of leucocytes to the endothelium at the site of
inflammation.
 Activation of leucocytes - release proteolytic enzymes and toxic
oxygen.
 Cause endothelial injury and increased vascular leakiness.
 Affects mostly venules and is a late response.

16. Leakiness and Neo-Vascularisation
Newly formed capillaries under the influence of vascular
endothelial growth factor (VEGF) during the Process of
repair and;
 in tumors are excessively leaky

17. CELLULAR EVENTS :
Consists of 2 processes
 Exudation of leucocytes.
 Phagocytosis.
Exudation of leucocytes
 Changes in the formed elements of blood.
 Rolling and adhesion
 Emigration
 Chemotaxis

18. CHANGES IN THE FORMED ELEMENTS OF BLOOD
 Central stream of cells comprised by
leucocytes and RBCs and peripheral
cell free layer of plasma, close to vessel
wall.
 Later, central stream of cells widens
and peripheral plasma zone becomes
narrower because of loss of plasma by
exudation.
 This phenomenon is known as
margination.
 Neutrophils of the central column
come close to the vessel wall –
pavementing.

19. ROLLING AND ADHESION
 Peripherally marginated and pavemented
neutrophils slowly roll over the endothelial cells
lining the vessel wall (rolling phase).
 Transient bond between the leucocytes and
endothelial cells becoming firmer (adhesion
phase).
 The following molecules bring about rolling and
adhesion phases –
-Selectins
-Integrins
-Immunoglobulin gene superfamily adhesion
molecule

20. EMIGRATION
 After sticking of neutrophils to
endothelium,
 The former move along the
endothelial surface till a suitable
site between the endothelial cells is
found where the neutrophils throw
out cytoplasmic pseudopods.
 Cross the basement membrane by
damaging it locally – collagenases
and escape out into the
extravascular space – emigration
 Diapedesis - escape of red cells
through gaps between the
endothelial cells

22. CHEMOTAXIS
 After extravasating from the blood, Leukocytes migrate toward sites of infection
or injury along a chemical gradient by a process called chemotaxis.
 They have to cross several barriers - endothelium, basement membrane,
perivascular myofibroblasts and matrix.
 Potent chemotactic substances or chemokines for neutrophils
– Leukotriene B4 (LT-B4)
arachidonic acid metabolites.
– Components of complement system - C5a and C3a in particular.
– Cytokines
– Interleukins, in particular IL-8

23. PHAGOCYTOSIS
The process of engulfment of solid particulate material by
the cells.
 2 main types of phagocytic cells –
- Polymorphonuclear neutrophils (PMNs)
- Macrophages
This phagocytic cells releases proteolytic enzymes -
lysozyme, protease, collagenase, elastase, lipase, proteinase,
gelatinase and acid hydrolases.

25. The microbe undergoes the process of phagocytosis in
following 3 steps : –
 Recognition and attachment
Engulfment
 Killing and degradation

26. RECOGNITION AND ATTACHMENT
 Phagocytosis is initiated by the expression of surface receptors on
macrophages.
 Its further enhanced when the microorganisms are coated with
specific proteins, opsonins.
 – Establish a bond between bacteria and the cell membrane of
phagocytic cell.
 – Major opsonins are
• IgG opsonin .
• C3b opsonin
• Lectins

27. ENGULFMENT
 Formation of cytoplasmic pseudopods around the
particle due to activation of actin filaments around cell
wall.
 Eventually plasma membrane gets lysed and fuses
with nearby lysosomes – phagolysosome.

28. FEATURES OF CHRONIC INFLAMMATION
Infiltration with mononuclear cells – macrophages, lymphocytes &
plasma cells.
Tissue destruction
Healing by Proliferation & connective tissue replacement of damaged
tissue

29. KILLING AND DEGRADATION
Killing of microorganism take place by Antibacterial
substances further degraded by hydrolytic enzymes
 Sometimes this process fails to kill and degrade some
bacteria like tubercle bacilli.

30. Disposal of microorganisms
Intracellular mechanisms –
 Oxidative bactericidal mechanism by oxygen free radicals
• MPO-dependent
• MPO-independent .
 – Oxidative bactericidal mechanism by lysosomal granules – Non-
oxidative bactericidal mechanism
Extracellular mechanisms
 Granules
 Immune mechanisms

31. CHRONIC INFLAMMATION
 Inflammation of prolonged duration (weeks to months to years)
in which active inflammation, tissue injury, and healing proceed
simultaneously.
Causes of Chronic Inflammation
• Following acute inflammation
• Recurrent attacks of acute inflammation
• Chronic inflammation starting de novo

32. HISTOPATHOLOGY OF GINGIVITIS AND PERIODONTITIS
Infiltration of the tissues by defense cells, neutrophils, macrophages, plasma cells, and
lymphocytes.
Accumulation of defense cells and the extracellular release of their destructive enzymes
There is disruption of the normal anatomy of the connective tissues resulting in collagen
depletion.
Vasodilatation and increased vascular permeability leads to increased leakage of fluid out of the
vessels, and
Facilitates the passage of defense cells from the vasculature into the tissues which appear
erythematous and edematous.

33. CHEMICAL MEDIATORS OF INFLAMMATION
 CELL- DERIEVED:
SOURCE MEDIATORS ACTION
MAST CELLS HISTAMINE VASODILATION.
INCREASE PERMEABILITY
PLATELETS SEROTONIN INCREASE PERMEABILITY
INFLAMMATORY CELLS PROSTAGLANDINS
LEUKOTRINES
LYSOSOMAL ACTIVITIES
CYTOKINES
VASODILATION
INCREASE PERMEABILITY.
TISSUE DAMAGE
TISSUE DAMAGE & FEVER

34. PLASMA-DERIEVED MEDIATORS
CLOTTING &
FIBRINOLYTIC
SYSTEM
FIBRIN SPLIT
PRODUCTS
INCREASE
PERMEABILITY
KININ SYSTEM KININ/
BRADYKININ
INCREASE
PERMEABILITY
COMPLEMENT
SYSTEM
ANAPHYLATOXINS INCREASE
PERMEABILITY

35. CYTOKOINES
 Protein that transmit signals from one cell to another.
 Also called INTERLUKINES
 Two types : PRO-INFLAMMATORY & ANTI-INFLAMMATORY
 PRO-INFLAMMATORY: Produced by activated macrophages &
involved in up- regulation of inflammatory reactions,
i.e.. Promotes inflammation
 ANTI-INFLAMMATORY: Immunoregulatory molecules that controls
pro-inflammatory cytokines response.

36. PRO-INFLAMMATORY CYTOKINES
TNF-α
• INCREASE CARTILAGE DEGRADATION
• BONE RESORPTION
• INDUCE APOPTOSIS
• STIMULATE PITHER CELLS TO STIMULATE CYTOKINES
IL-1β
• INHIBIT PROTEOGLYCAN SYNTHESIS
• UPREGULATE MMP EXPRESSIONS
• STIMULATE PRO-ANGIOGENIC FACTOR RELAESE
IL-6
• REDUCE CHONDROCYTE PROLIFERATION
• INCREASE MMP-2 ACIVITY
• INCREASE AGGRECANASE MEDIATED PROTEOGLYCAN
ACTIVITY

37. ANTI-INFLAMMATORY
IL-Ra INHIBIT IL-1α IL-1β MEDIATED RESPONSES
IL-4 • PROMOTTES Th-2 LYMPHOCYTES DEVT.
• INHIBITION OF LPS-INDUCED PRO-INFLAMMATORY CYTOKINE
SYNTHESIS
IL-6 INHIBITION OF TNF & IL-1 PRODUCTION BY MACROPHAGES
IL-10 INHIBITS MONOCYTES/ MACROPHAGES & NEUTROPHIL CYTOKINES
IL-11 • INHIBITS MONOCYTES/ MACROPHAGES & NEUTROPHIL CYTOKINES
• PROMOTTES Th-2 LYMPHOCYTES DEVT.
IL-13 ALTERATION OF MONOCYTE/ MACROPHAGE FUNCTIONS
TGF-β INHIBITS MACROPHAGE CLASE II EXPRESSION

38. AUTHOR &
JOURNAL
TITLE RESULT CONCLUSION LEVEL OF
EVIDENCE
• Amanda F.
Stadler et al.
(2016)
• JOURNAL OF
CLINICAL
PERIODONTTOLOGY
Gingival
crevicular fluid
levels of
cytokines/chemo
kines in chronic
periodontitis: a
meta-analysis.
GCF levels of IL-
1b, IL-6 AND
IFN-c were
significantly
higher in subjects
diagnosed with
Chronic
Periodontitis
than
periodontally
healthy subjects.
Evidence for
significant
differences
between
periodontal
health and
Chronic
Periodontitis
was observed for
a few cytokines
and one
chemokine.
1a

39. MATRIX METTALOPROTEINASE
 It is a family of proteolytic enzymes that degrade extracellular matrix
molecules such as collagen , gelatin and elastin.
 It is produced by variety of cells including macrophages, neutrophils,
fibroblasts, epithelial cells, osteoclasts.
MMP-1 COLLAGENASE 1
(INTERSTITIAL COLLAGENASE)
CLEAVE THE TRIPLE HELIX OF
FIBRILLAR COLLAGEN
MMP-8 COLLAGENASE 1
(NEUTROPHIL COLLAGENASE)
DEGRADE TYPE 1 COLLAGEN
MMP-9 GELATINASE DEGRADE TYPE I,II,III
COLLAGEN

40. PROSTAGLADINS
 Lipid components derived from arachidonic acid.
 Mediated by cyclo-oxygenase and lipo-oxygenase pathway
PGI2, PGE2, PGD2 1 • Vasodilation
• Decrease Platelet aggregation,
• Leukocyte aggregation,
• T-cell proliferation,
• IL-1 and IL-2, lymphocyte migration
PGF2a ↑ Vasoconstriction
TXA2 • ↑ Vasoconstriction,
• Platelet aggregation,
• Lymphocyte proliferation

42. RESOLUTION OF INFLAMMATION
 It is an active process that results in a return to normal haemostasias, and is
mediated by specific molecules including a class of endogenous lipid
mediators, lipoxins, resolvins and protectins.
 Lipoxins: LX A4, B4. They also signal macrophages to phagocytose the
remnants of apoptotic cells at sites of inflammation, without generating an
inflammatory response.
 Resolvins : They inhibit neutrophilic infiltration and transmigration, they
inhibit production of inflammatory mediators.
 Protectins: They reduce cytokine expression and also inhibit neutrophilic
infiltration.

43. CONCLUSION
 Inflammation is a vital part of the immune system's response to injury and
infection.
 It is the body's way of signalling the immune system to heal and repair
damaged tissue, as well as defend itself against foreign invaders, such as
viruses and bacteria.
 A better understanding of inflammatory response pathways and molecular
mechanisms will undoubtedly contribute to improved prevention and
treatment of inflammatory diseases.

44. REFERENCES
 Stadler AF, Angst PD, Arce RM, Gomes SC, Oppermann RV, Susin C.
Gingival crevicular fluid levels of cytokines/chemokines in chronic
periodontitis: a meta‐analysis. Journal of clinical periodontology. 2016
Sep;43(9):727-45.
 Mohan H. Textbook of pathology. Jaypee Brothers Medical Publishers;
2015.
 Carranza F, Henry H, Newman M. G Clinical periodontology 10th edition.
 Lindhe J, Karring T, Lang NP. Periodontologia clinica e implantologia
odontologica/Clinical Periodontology and Implant Dentistry. Ed. Médica
Panamericana; 2009 Jun 30.
 Dennison DK, VAN DYKE TE. The acute inflammatory response and the
role of phagocytic cells in periodontal health and disease. Periodontology
2000. 1997 Jun;14(1):54-78.

45. THANKYOU!