inflammation, immunity, cells of immunity & inflammation, hypersensitivity reactions.

1. IMMUNITY &
INFLAMMATION
Guided By: Presented By:
DR. K.S. STELIN (HOD) DR. MARIYAM MOMIN
DR. PARUL ANEJA (READER) I YEAR PG
DEPARTMENT OF PERIODONTOLOGY & ORAL IMPLANTOLOGY.

2. CONTENTS
 Inflammation
 Immunity
 Cells of immunity & inflammation
 Immunoglobulins
 Complement
 Chemical mediators of inflammation
 Immune responses
 Immune mechanisms
 References

3. INFLAMMATION
 Inflammation refers to tissue injury or
irritation, initiated by the entry of
pathogens or other irritants – Kumar V
et.al. (2005).
 Inflammation is defined as a local
response of living mammalian tissues
to injury due to any agent.
 It is a body defense reaction in order
to eliminate or limit the spread of
injurious agent as well as to remove
the consequent necrosed cells and
tissues.

4. SIGNS OF INFLAMMATION
4 cardinal signs of
inflammation by
Celsus
Rubor (redness)
Tumor (swelling)
Calor (heat)
Dolor (pain)
Redness
Pain
Swelling
Warmth

5. 5th sign was later
introduced by Galen
Functio laesa (loss of function)
Rudolf Virchow

6. TYPES OF
INFLAMMATION
INFLAMMATION
ACUTE
INFLAMMATION
CHRONIC
INFLAMMATION
Features Acute inflammation Chronic inflammation
Causative agent Pathogens, injured
tissues
Persistant acute
inflammation due to non-
degradable pathogens,
persistant foreign bodies
or autoimmune reactions.
Major cells involved Mainly neutrophils Mononuclear cells
(monocytes,
macrophages,
lymphocytes, plasma
cells), fibroblasts.
Primary mediators Vasoactive amines,
ecosanoids
IFN-ꙋ and other cytokines,
growth factors, reactive
oxygen species, hydrolytic
enzymes.
Onset Immediate Delayed
Duration Few days Upto many months or
years
Outcomes Resolution, abscess
formation, chronic
inflammation.
Tissue destruction,
fibrosis, necrosis.
Difference between acute and chronic inflammation

7. IMMUNITY
 Immunity refers to the resistance exhibited by the host towards
injury caused by microorganisms and their products.

8. Types of immunity
Immunity
Active
Immunity
Natural
Immunity
Induced
Immunity
Innate
Immunity
Passive
Immunity
Artificial Natural Artificial Natural

10. Difference between Active & Passive
immunity
S.No. Feature Active immunity Passive immunity
1 Production Produced actively by
immune system
Received passively by
host. The host’s immune
system does not
participate.
2 Induction Induced by infection or by
contact with
immunoglobulin
Conferred by
administration of ready-
made antibodies
3 Duration Long lasting & effective Short lived & less
effective
4 Effectiveness Effective only after a lag
period
Effective immediately
5 Immunological
memory
Present Absent
6 Uses For prophylaxis to increase
body resistance
For treatment of acute
infections

11. CELLS OF IMMUNITY &
INFLAMMATION
MACROPHAGES
 Develop from blood monocytes,
which emigrate into tissues from the
blood and are triggered to develop
as cytokines, other inflammatory
mediators, bacterial products such
as endotoxins.
Macrophage

12. MAST CELLS
 Mast cells are the cells concerned
with immunity and immediate
inflammation.
 Inflammatory mediators of mast
cells
- Mast cells possess cytoplasmic
granules called as lysosomes
which store the following
mediators:
1. TNF-α
2. Heparin
3. Histamine
4. Leukotriene B4
5. Neutrophil chemotactic factor
6. Eosinophilic chemotactic factor
7. Slow releasing substances of
anaphylaxis (SRS-A).

13.  Role of mast cells in gingiva
1. The cytoplasmic granules
contain heparin and histamine.
The physiologic role of heparin
in mast cells does not appear
to be clear.
2. Greater number of mast cells
are found in inflamed gingiva
as compared to healthy
gingiva.
3. Mast cell histamine plays a role
in the inflammatory reaction
and they have shown to
degranulate in response to
antigen-antibody formation on
their sueface.

14. NEUTROPHILS
 Synonym – Polymorpho nuclear
leukocytes (PMNs)
 Neutrophils are the frontline
soldiers in inflammation. They are
the first line of defense cells in
gingiva.
 Trans-endothelial migration.
 Neutrophil granules
- Primary granules/ azurophilic
granules
- Secondary/ specific granules
- Tertiary granules.

15. Functions of neutrophils
Destructive mechanism
- Emigration & chemotaxis
- Phagocytosis.
Protective mechanism
- Magnify inflammation
- Activate kinin producing system
- Activate complement components
via alternativa pathway
- Carry potent substances
- Responsible for destruction of
collagen & other connective tissue
substances including bone
resorption.

17. Mechanism of phagocytosis

18. Oxidative mechanism of
phagocytosis

19. NEUTROPHIL DISORDERS
Neutrophil disorders associated with periodontal
diseases
Diabetes mellitus Cyclic neutropenia
Down’s syndrome
Chediak – Higashi syndrome
Papillon lefevre syndrome
Drug induced agranulocytosis

20. Periodontal diseases associated with neutrophil
disorders
- Refractory periodontitis (RP)
- Pre-pubertal periodontitis (PPP)
- Localized juvenile periodontitis (LJP)
- Rapidly progressive periodontitis (RPP)
- Acute necrotizing ulcerative gingivitis (ANUG)
Neutrophil defects associated
with aggressive periodontitis
- Abnormalities in adherence – LAD-1 &
LAD-2
- Abnormalities in chemotaxis – Chediak-
Higashi syndrome
- Abnormalities in phagocytosis &
intercellular killing.

21. LYMPHOCYTES
Lymphocytes
NK cells B cells T cells
CD4+ CD8+

22. IMMUNOGLOBULINS
 Synonym – Antibodies
 Definition
- Immunoglobulin is a glycoprotein composed
of heavy & light peptide chains; functions as
antibody in serum and secretions – PLR.
 Types of immunoglobulins & its functions
S.No. Immunoglobulin Function
1 IgA Mucosal defense
2 IgD Activates B cells
3 IgM Acts as agglutinins &
activates complement
4 IgG4 & IgE Acts against parasites &
anti-inflammation
5 IgG1, IgG2, IgG3 Acts as opsonin &
complement activation.

23. COMPLEMENT
 Complement is an interacting
network of about 30 membrane
associated cell receptors and
soluble serum glycoprotein –
Carranza
Activation
path
Sequence of
activation
Classical
pathway
C1, C2, C3, C4,
C5, C6, C7, C8 &
C9.
Alternative
pathway
C3, C5, C6, C7, C8
& C9.
Pathways of activation of
complement

25. Effects of complement
S.No. Component Activity
1 C1 & C9 Cytolytic & cytotoxic damage to cells
2 C2 & C3a Kinin activity
3 C3 & C4 Promotion of clot lysis
4 C3 & C5 Promotion of phagocytosis
5 C5a Lysosomal enzyme releasing from leukocytes
6 C6 Enhancement of blood clotting
7 C5 & C6 Inactivation of bacterial lipopolysaccharides
from endotoxin
8 C3a, C5a & C567 Chemotactic activity for leukocytes
9 C3a & C5a Histamine release from mast cells & increase
vascular permeability.

26. CHEMICAL MEDIATORS OF
INFLAMMATION
Chemical mediators
of inflammation
Cell-derived
mediators
Preformed mediators in secretory
granules (histamine, serotonin)
Newly synthesized granules
(prostaglandins, cytokines, nitric
oxide & oxygen metabolites)
Plasma-derived
mediators
Complement system derived
(anaphylatoxins)
Kinin system derived (bradykinin)
Clotting system derived (fibrin
split products)

27. Cell derived mediators
 Histamine – main actions are vasodilatation & increase
permeability.
 Serotonin (5-HT) – actions are similar to histamine.
Prostaglandins (PGE)
Macrophages &
fibroblasts
IL-1𝛽, TNF-𝛼 &
bacterial LPS
Upregulation of
COX-2
Production of PGE-2
Production of PGE-2 Tissue destruction in PGE-2
PGE-2
Acts on fibroblasts & osteoclasts
PGE-2 long with cytokines
Production of MMP
Tissue turnover
Periodontal destructive process

28. Effects of PGE
- Vascular dilatation & erythema
- Increased vascular permeability
- Induction of platelet aggregation by cyclic
endoperoxides
- Chemotaxis of PMNs & macrophages
- Cytotoxicity of fibroblasts.
- PGE-2 is associated with inflammation &
attachment loss.
- PGE-2 is elevated in gingivitis & periodontitis.
- PGE-2 appears to be partly responsible for the
bone loss associated with periodontitis..
- Analysis of PGE-2 in GCF may eventually be
considered as a diagnostic marker for future bone
loss.
- Inhibition of lymphocyte transformation &
cytotoxicity.
- Inhibition of antibody secretion with high
concentration of prostaglandins.
- Inhibition of IgE mediated release of
mediators from mast cells & basophils.
PGE in inflammation
PGE in immunity
PGE in periodontal
diseases

29. Effects of prostaglandins
S.No. Acts on Effects
1 Osteoblasts To inhibit bone formation
2 Osteoclasts To induce bone resorption
3 Fibroblasts To produce MMP which
degrade soft connective
tissue component
4 Monocyte /
macrophages
Increases the production
of inflammatory cytokines
in response to bacterial
endotoxins
5 Blood vessels To dilate the vessels &
increase the inflammatory
fluid at the site, resulting
stasis
6 Collagen
synthesis
Inhibition of bone
formation by inhibition of
collagen synthesis.

30. CYTOKINES
 Cytokines are the small protein
messengers released by the cells
which affect the division, differentiation
& function of other cells, which may be
of the same or different types.
 All these biologically active substances
lymphokines, monokines & interleukins
are collectively known as cytokines.
Cytokines Produced by
Lymphokines Lymphocytes
Monokines Monocytes & macrophages
Interleukins Lymphocytes, monocytes,
keratinocytes, macrophages,
fibroblast, platelets.
Production of cytokines

31. Cytokines in periodontal diseases
S.No, Action Cytokines
1 Pro-inflammatory IL-1, IL-6, IL-8, TNF-𝛼 & IFN-𝛼
2 Anti-inflammatory IL-4, IL-10, IL-13 & TGF-𝛼
3 Scarring IL-6 & TGF-𝛼
4 Anti-scarring IL-10
5 Angiogenic IL-8 & angiogenins
6 Anti-angiogenic IL-10

32. Nitric oxide – causes vasodilatation, antiplatelet activating agent &
microbicidal action.
Plasma derived mediators
Anaphylatoxins
Complement peptides C3a,C4a,
C5a which can cause smooth
muscle contraction, incease
vascular permeability & histamine
release from mast cells.
Thrombin
It is a serine protease that
converts soluble fibrinogen into
insoluble fibrin.
Plasmin
It is a proteolytic enzyme that acts
to break down fibrin clots, leave
complement protein C3 & activate
factor XII.
Bradykinin
It is a short-lived, vasoactive
peptide that is able to induce
vasodilation, increase vascular
permeability, cause smooth
muscle contraction & induce pain.

33. Immune Responses
 The specific reactivity induced in a host following an antigen
stimulus is called as immune response.
Types
 Humoral immunity
 Cell mediated immunity

34. IMMUNE MMECHANISMS
Immune
reactions
Type I
Anaphylactic
reaction
Type II
Cytotoxic
reaction
Type III
Arthu’s reaction
Type IV
Delayed
hypersensitivity

36. Anaphylactic reaction
IgE + mast cell
Binds to Fab portion of
IgE
Sensitization of mast
cell
Stimulation of mast cell
Release of
inflammatory mediators

37. Cytotoxic reaction
Ag/ haptens attached to
tissue / cell membranes
IgG/IgM antibodies
produced
Complement activated
analysis
Phagocytosis
Lysis by the effects of
lymphoid cells

38. Arthu’s reaction
Immune complex deposited
on the basement
membrane of blood vessels
Activation of complements
Neutrophil activation
Liberation of lysozomal
enzymes
Destruction of basement
membrane

39. Cell mediated immunity
Antigen
T-cell sensitization
& activation
Release of
cytokines

40. Pathogenic immune reactions
S.No. Type Immune
reactions
Mechanism Example
1 Type I Anaphylactic Antigen reacts with cells
sensitized by IgE antibodies &
release mediator
Food allergies
Urticaria
Hay fever
2 Type II Cytotoxic Antibody reacts with cell
associated antigen usually, but
not always, kills cells with the
help of complement or
phagocytic cells.
Transfusion
reactions
Autoimmune
reactions
3 Type III Arthu’s reaction Antibody reacts with antigen
in tissue spaces or blood
stream to cause vasculitis
requires complement.
Serum sickness
Arthu’s reaction
4 Type IV Delayed
hypersensitivity
Lymphocytes reacts with
antigen.
Tuberculin
reaction
Contact
dermatitis
Allograft
rejection.

41. Comparison of different types of
hypersensitivity
S.No. Characteristics Type I Type II Type III Type IV
1 Antibody IgE IgG, IgM IgG, IgM None
2 Antigen Exogeous Cell surface Soluble Tissues &
organs
3 Response time 15-30
minutes
Minutes -
hours
3-8 hours 48-72 hours
4 Appearance Wheal &
flare
Lysis &
necrosis
Erythema,
edema &
necrosis
Erythema &
induration
5 Histology Basophils &
eosinophils
Antibody &
complement
Complement
& neutrophils
Monocytes &
lymphocytes
6 Transferred with Antibody Antibody Antibody T-cells
7 Examples Hay fever
Allergic
asthama
Erythroblast
osis fetalis
Good
pasture’s
nephritis
SLE
Farmer’s
lung disease
Poison ivy
Granuloma
Tuberculin
test

42. Impact of micro-oraganisms on
immunity & inflammation
S.No. Microbes & products Impact on inflammation & immunity
1 Microbes Are antigenic
Activate complement
Activate neutrophils & macrophages
2 Proteins & peptides Are antigenic
Chemotactic for neutrophils &
macrophages
3 Lipopolysaccharides Are antigenic
Activate complement
Damage host cells & alveolar bone
resorption
4 Polysaccharide plaque
matrix
Are antigenic
Polyclonal B-cell activator
5 Enzymes Are antigenic
Degrade antibody
Damage host cell
Degrade connective tissue matrix
Activate & degrade complement.

43. Influence of host response on
periodontal diseases
S.No. Aspect of disease Host factors
1 Bacterial colonization Subgingivally antibody & complement in GCF
inhibits adherence & coaggregation of bacteria
& potentially reduces their numbers by lysis.
2 Bacterial invasion Antibody – complement mediates lysis reduces
bacterial counts.
Neutrophils as a consequence of chemotaxis,
phagocytosis & lysis reduces bacterial counts.
3 Tissue destruction By antibody mediated hypersensitivity & cell
mediated immune responses.
Activation of tissue destructio factors such as
collagenase.
4 Healing & fibrosis Lymphocytes & macrophages produce
chemotactic factors for fibroblasts, fibroblast
activationg factor.

44. References
 Carranza’s Clinical Periodontology- 10th Edition.
 Essentials of Periodontology – (Sahitya Reddy S)
 Textbook of Periodontics – Shalu Bathla (2nd Edition).

45. Thank You.