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GOOD
AFTERNOON
INFLAMMATION
PRESENTED BY
R.VYSHNAVI
1 S T YEAR POSTGRADUATE
DEPARTMENT OF PERIODONTICS
CONTENTS:
• INTR OD UC TION

• H ISTORY

• SIGN S OF IN FL A M M ATION

• TY PE S OF INF L A MM ATION

• M ECH A NISM

• SY STE MI C EFF EC TS OF INFL A M M ATI ON

• A PPL IED ASPEC TS

• GIN GIVAL A N D PERIOD ON TA L IN FL A M M ATION

• REFE REN C ES
INTRODUCTION:
• Infl a m m a tion is d efi ne d a s th e l oca l re spons e
of liv in g m a m m al ia n ti ss ues t o in jur y due t o
a ny a g e nt . It is a body def en se re a ct ion in
orde r to e li m ina te or li m it t he sp rea d of
in jur iou s a g e nt , foll owe d by rem ova l of th e
ne cr osed c el ls an d tis su es .
AGENTS CAUSING INFLAMMATION:
The a g en ts ca u sin g infl a m m a tion m ay be a s un der :

1. Inf ec ti ve ag e nt s l ike ba ct eri a , v ir us es an d th eir t oxi ns, fun g i, pa ras ite s.

2. Imm un ol og ic a l a g e nt s like ce ll - m edi a ted a nd an ti g en-a nt ib od y r ea ct ions .

3 . Phy sic a l ag e nt s like he at , col d, ra di at ion, m ec ha ni ca l tra um a .

4 . Ch em ic a l a g e nt s l ike org a ni c an d i nor g a nic poi son s.

5 . In er t m at er ial s su ch a s fore ig n bod ies .

HISTORICAL HIGHLIGHTS:
• Cl in ic al fe a tur es wer e 1s t d es cr ibe d i n an Eg y pti a n papy ru s( 3 00 0 B C )

• Ce lsu s in 1 st c ent ur y A D g av e t he 4 c ar din al s ig n s of i nfl a m m at ion:

A) Rubo r ( r e dne s s)

B) Tum or ( sw el l ing )

C) Ca lor ( he a t)

D ) D ol or ( p a in)

5 th si g n : Funct i o-la e s a ( l oss of fun c tion) -

a dded by V ir c how ( 19 t h C EN TURY )

• In 1 79 3, J ohn Hu nt er st at ed th at ” in fl a m m a ti on i s n ot a dis ea se bu t a non- s pec ifi c
re spon se th at h as a s al uta r y e ff ec t on i ts hos t ”.

• In 1 88 0’s, M e tc hin koff - Pha g oc y tos is

TYPES OF INFLAMMATION:
Depending upon the defense capacity of the host and duration of response:

ACUTE INFLAMMATION CHRONIC INFLAMMATION

• Sh or t d urat ion ( la st in g l es s t ha n • long e r durat ion

2 we ek s )
• Oc cu rs ei th er a f t er t he
• Repr es en ts th e ea rly body ca us at ive a g en t of a cu te
re ac ti on , r esol ves qu ic kl y an d i s infl a m m a tion pe rsi st s for a long
usu al ly f ol lowed by hea l ing . tim e , or the s ti m ulu s is s uch
tha t it in du ce s ch roni c
infl a m m a tion fr om t he
beg i nn in g .
ACUTE INFLAMMATION CHRONIC INFLAMMATION

• MA I N FEATU RES: • MA IN F EAT URES:

1. a c c um ul at ion of fl u id a nd • Pr esence of c hroni c infl amm ator y

pla sm a at th e aff ec t ed sit e cel ls su ch as ly mphocy tes,
plasm a c ells and ma cropha ges ,
2 . i ntrava s cul a r a c ti va ti on of
granulat ion t issue form ation
pla te le ts ; an d
• In speci fi c situ ations as
3. p oly m or phon ucl ea r ne utr ophi ls granulom atous in fl amm ati on
as i nfl am m at or y ce lls .
 ACUTE INFLAMMATION CHRONIC INFLAMMATION

• Som e ti m es, th e a c ute • A var ia nt - chr oni c ac ti ve

infl a m m a tor y r esp on se m ay be
qui te se ver e an d i s ter m ed as
fu lm in a nt ac ut e infl a m m a ti on .
infl a m m a tion , is t he ty p e of
ch roni c infl am m a ti on i n wh ic h
dur ing t he cou rs e of di se as e
the re a re a cu te exa ce rb at ions of
ac ti v it y.

In some instances, the term subacute infl ammation is used for the
state of infl ammation between acute and chronic
ACUTE INFLAMMATION:
• Can be di v i ded in to foll owi ng two e ve nt s:

I. Vas cu la r eve nts .

II. C e ll ula r eve nt s.

VASCUL A R EVE NTS:

A lt era tion i n t he m ic r ovas cu la t ure ( a r ter iole s, c a pil la ri es a nd venu le s) is th e

ea rl ie st re spon se to t is su e i nj ur y. Th es e al tera ti ons in c lud e:

HAEMODYNAMIC CHANGES:
Alterations in vessel caliber
Changes in vessel wall

CHANGES IN VASCULAR PERMEABILITY

CELLULAR EVENTS:
• The c ell ul ar p ha se of infl a m m at ion con si sts of 2 pr oc e ss es:

1 . e xu da ti on of le uc ocy tes ; a nd

2 . ph a g ocy t osis .
VASCULAR CHANGES:
a) H E M O D Y N A M I C C H A N G E S : With mild form of injury, the blood flow
may be re-established in 3-5 seconds
T R A N S I E N T VAS O C O N S T R I C T I O N while with more severe injury the
vasoconstriction may last for about 5
minutes

• Mainly the arterioles

• Within half an hour of injury
P E R S I S T E N T P R O G R E S S I V E VAS O S D I L AT I O N
• Results in increased blood volume
in microvascular bed of the area
• Responsible for redness(RUBOR)
and warmth(CALOR) at the site of
acute inflammation.

E L E VAT E L O C A L H Y D R O S TAT I C P R E S S U R E resulting in transudation of fluid into

the extracellular space
swelling(TUMOR)
SLOW ING OR STASIS OF M IC ROC IRC UL ATION follows which causes increased
concentration of red cells, and
thus, raised blood viscosity.

• mainly neutrophils – migrate

L E UC OC YTIC MI GRATION along the vascular
endothelium.
• leucocytes stick to the vascular
endothelium briefly, and then
move and migrate through the
gaps between the endothelial
E M IGRATION OF L EU CO CY TES cells into the extravascular
space
LEWIS EXPERIMENT:
Lewis induced the changes in the skin of
i n n e r a s p e c t o f f o r e a r m b y fi r m s t r o k i n g w i t h
a blunt point reaction known as TRIPLE
RESPONSE OR RED LINE RESPONSE.

i)Red line appears within a few seconds

following stroking and is due to local
vasodilatation of capillaries and venules.

ii) Flare is the bright reddish appearance or

fl u s h s u r r o u n d i n g t h e r e d l i n e a n d r e s u l t s
from vasodilatation of the adjacent arterioles.

iii) Wheal is the swelling or oedema of the

surrounding skin occurring due to
t r a n s u d a t i o n o f fl u i d i n t o t h e e x t ra v a s c u l a r
space.

MICROSCOPIC FEATURES
ALTERED VASCULAR PERMEABILITY:
• Several mechanisms are responsible for the increased permeability of
postcapillary venules, a hallmark of acute infl ammation.

• In acute infl ammation, normally non-permeable endothelial layer of

microvasculature becomes leaky.

• The most prevalent mechanism of vascular leakage is endothelial cell

contraction, which results in greater inter-endothelial gaps.

• Histamine, bradykinin, leukotrienes, and other chemical mediators cause it.

• The immediate transient response is named from the fact that it begins quickly
af ter exposure to the mediator and is generally shor t-l ived (15 to 30 mi nutes).

• Vascular leakage begins af ter a delay of 2 to 12 hours and lasts for several hours
or even days in some forms of mild injur y (e.g., af ter burns, irradiation or
ultraviolet radiation, and exposure to cer tain bacterial toxins); this delayed
prolonged leakage may be caused by contraction of endothelial cells or mild
endothelial damage. This form of leakage is a good example of late-appearing
sunburn.

• Endothelial injur y, resulting in endotheli al cell necrosis and detachment . Direct

damage to the endothelium is encountered in severe injuries, for example, in burns,
or is induced by the actions of microbes and microbial toxins that target endothelial
cells.
 Principal mechanisms of increased vascular permeability in
infl ammation and their features and underlying causes
• Neutrophils that adhere to the endothelium during infl ammation may also injure the
endothelial cells and thus amplify the reaction. In most instances leakage star ts
immediately af ter injur y and is sustained for several hours until the damaged vessels
are thrombosed or repaired.

• Increased transpor t of fl uids and proteins, called TRANS CYTOSIS , through the
endothelial cell. This process may involve intracellular channels that may be
stimulated by cer tain factors, such as vascular endothelial growth factor (VEGF), that
promote vascular leakage.

• However, the contribution of this process to the vascular permeability of acute

infl ammation is uncer tain.
• In addition to blood vessels, lymphatic vessels also par ticipate in acute infl ammation.
The system of lymphatics and lymph nodes fi lters and polices the extravascular
fl uids.

• Lymphatics normally drain the small amount of extravascular fl uid that has seeped
out of capillaries.

• In infl ammation, lymph fl ow is increased and helps drai n edema fl uid that
accumulates because of increased vascul ar permeabili ty .

• In addition to fl uid, leukocytes and cell debris, as well as microbes, may fi nd their
way into lymph.

• Lymphatic vessels, like blood vessels, proliferate during infl ammator y reactions to
handle the increased load.
• The lymphatics may become secondarily infl amed ( lymphangitis ), as may the
draining lymph nodes ( lymphadenitis ).

• Infl amed lymph nodes are of ten enlarged because of hyperplasia of the lymphoid
follicles and increased numbers of lymphocytes and macrophages is seen.

• This constellation of pathologic changes is termed reacti ve, or infl ammator y ,

lymphadeniti s.

• The changes in blood fl ow and vascular permeability are quickly followed by an

infl ux of leukocytes i nto the tissue which per form the key function of eliminating
the off ending agents.

• The most impor tant leukocytes in typical infl ammator y reactions are the ones capable
of phagocytosis, namely neutrophils and macrophages .
• These leukocytes ingest and destroy bacteria and other microbes, as well as necrotic
tissue and foreign substances.

• Leukocytes also produce growth factors that aid in repair.

• A price that is paid for the defensive potency of leukocytes is that, when strongly
activated, they may induce tissue damage and prolong infl ammation, because the
leukocyte products that destroy microbes and help “clean up” necrotic tissues can
also injure normal bystander host tissues.
CELLULAR EVENTS
 EXUDATION OF LEUKOCYTES:
• The journey of leukocytes from the vessel lumen to the tissue is a multistep process
that is mediated and controlled by adhesion molecules and cytokines called
chemokines.

• This process can be divided into sequential phases

1. In the lumen: MARGINATION, ROLLING, and ADHESION TO ENDOTHELIUM .

Vascular endothelium in its normal, inactivated state does not bind circulating cells or
impede their passage. In infl ammation, the endothelium is activated and can bind
leukocytes as a prelude to their exit from the blood vessels.

2. Migration across the endothelium and vessel wall

3. Migration in the tissues toward a chemotactic stimulus.

MARGINATION AND
ROLLING AND ADHESION
PAVEMENTING

EMIGRATION
LEUCOCYTE MIGRATION
• In normally fl owing blood in venules, red cells are confi ned to a central axial column,
displacing the leukocytes toward the wall of the vessel. Because blood fl ow slows
early in infl ammation (stasis), hemodynamic conditions change (wall shear stress
decreases), and more white cells assume a peripheral position along the endothelial
sur face.

• This process of leukocyte redistribution is called MARGINATION . Subsequently,

leukocytes adhere transiently to the endothelium, detach and bind again, thus rolling
on the vessel wall. The cells fi nally come to rest at some point where they adhere
fi rmly (resembling pebbles over which a stream runs without disturbing them).

• The attachment of leukocytes to endothelial cells is mediated by complementar y

adhesion molecules on the two cell types whose expression is enhanced by cytokines.
Cytokines are secreted by sentinel cells in tissues in response to microbes and other
injurious agents, thus ensuring that leukocytes are recruited to the tissues where
these stimuli are present.
• The two m a jor fa mil ie s of m ol ec ul es inv ol ved in l eukocy te ad he sion a nd m ig ra ti on ar e the
se le ct in s a nd in te g r ins , a nd the ir l ig a nd s. The y ar e e xpre ss ed on l eu koc y te s an d
en doth el ial c el ls .

1. SEL E CTIN S: m e dia te s th e in iti al r ol li ng in tera c ti ons. Ther e a re t hr ee ty pes of se lec t ins :
L- s e le c ti n : one e xpr e s se d on le uko cy te s

E-se l ec ti n : one o n e ndo the li um a n d

P-se l ec ti n : one i n p l at e le ts and o n e ndo the l ium

• The li g a nds fo r s ele c tin s ar e sia l y la te d ol ig osa c ch ar id es

b ou nd to m uc in -l ike g lyc opr ot ei n b ac k bone s.

• Th e e xpre ss ion of s el ec ti ns a nd t he ir l ig a nds i s reg ula t ed by c y t oki ne s p rodu ce d i n
re spon se to i nf ec ti on an d i nju r y.

• Tiss ue m a c ropha g e s, m a st c el ls , a nd end ot he li al c el ls tha t e nc ou nt er m ic robe s an d dea d

ti ssu es r es pond by s ec r eti ng se vera l cy tok i nes , i ncl ud ing t um or ne cr o si s f a ct or ( T NF) ,
I L-1 , an d che m oki ne s ( c hem oa t tra ct a nt cy tok i nes ) .

• Wit hi n 1 to 2 h ou rs , t he en dothe li al c el ls be g in to expr ess E - se le ct in an d t he l ig a nds f or

L-se le ct in.

• Ot he r m edi at or s su ch a s his ta m in e an d t hro m bin , st im u lat e th e r ed ist ri but ion of P-

se le ct in fr om it s nor m al in tra c ell ul ar st ores i n en doth eli al c el l g ran ul es ( ca l led Wei bel -
Pa la de bodi es) to th e c el l s ur fa c e.
• L eu koc y te s expr es s L- s el ec tin a t th e t ip s of t hei r m ic rov il li a nd al so expr ess l ig a nd s f or E -
a nd P- sel ec ti ns , al l of wh ic h bin d to th e com pl em e nta r y m ole c ule s on t he en doth el ia l
cell s.

• Th es e a re l ow-affi ni ty in tera c tion s wi th a f as t off - rat e, a nd th ey ar e ea si ly di sru pte d by

th e fl owi ng blood.

• A s a re sul t, th e b ou nd le ukocy t es bi nd, det ac h, an d b ind a g a in, an d t hu s b eg i n t o r oll

a long th e en dothe lia l su r f ac e .

• Th e we ak roll in g i nt erac t ions sl ow down th e leu koc y te s an d g ive th em the opp or tu ni ty to

bin d m or e fi rm l y t o th e end ot he li um wh ic h is m edi a ted by a fa m il y of h et erodi m er ic
le ukocy te su r f ac e prot ei ns ca ll ed I NT EGR I NS .
• TNF a nd IL- 1 in duce en doth eli al e xpre ssi on of l ig a nd s f or i nt eg r in s, m a in ly va s cu la r ce ll
a dhe sion m ole c ule 1 ( VC A M - 1)

• L eu koc y te s norm a ll y expre ss i nte g r ins i n a l ow-a ffi n ity st at e.

• Chem o ki ne s t ha t we re p roduc ed a t t he si te of in jur y bin d to e ndot hel ia l ce ll pr ot eog l yca ns

a nd ar e d is played at h ig h c on c en trat ion s on th e en doth eli al s ur fa ce .

• The se ch em ok i nes bi nd to a nd a c tiva te th e r olli ng l eukocy te s.

• The c om b in at ion of c y t ok i ne- in duc ed expr ess ion of in teg ri n l ig a nd s on t he en dothe l ium
a nd inc r ea sed in te g r in affi nit y on t he le ukocy t es r esu lt s in fi r m i nt eg r in - m edi at ed
a dhe sion of th e leu koc y t es to the e ndoth el iu m a t t he s it e of i nfl am m a ti on.

• The le ukocy tes s top roll in g , th ei r cy t oskel eton is r eor g an iz ed, an d t hey s pre ad out on th e
en doth el ial s ur fa c e.
Leukocyte Migration Through Endothelium
• The ne xt ste p i n th e p roce ss of le ukocy t e re cru it m en t i s m ig rat ion of t he le ukocy t es
th roug h int ac t en dothe l ium , ca ll ed TR A NSMIGR ATION O R DI A P ED ESI S.

• Tran sm i g ra tion of le ukoc y t es oc cur s m a inl y i n post ca pi lla r y ve nul es .

• Ch em ok in es ac t on th e a dh ere nt l eukoc y te s a nd st im u la te t he ce ll s to m i g ra te th roug h

in te r- en doth eli al g a ps t owa rd th e ch em ic a l conc en tra ti on g rad ien t, tha t is , towar d the s ite
of inj ur y or in fe ct ion whe re th e c h em ok in es ar e bei ng pr od uce d.

• Several a dhe si on m ol ec ul es pre se nt in t he in te rc ell ul ar j unc ti ons be twee n e nd ot he li al c ell s

a re invol ved in t he m ig ra ti on of l eu koc y te s.

• The se m ole cul e s i nc lu de a m em be r of t he i m m unog l obul in su pe r f am i ly ca ll ed C D 31 or

PECA M - 1 ( pl at ele t end othe li al c el l adh es ion m ol e cul e) .
• A f t er traver sin g the e ndot hel iu m , le ukocy tes pi er ce t he ba se m ent m e m bra ne, proba bl y
by se cr et ing c ol la g en a se s, a nd en ter t he e xt ravas cu la r sp ac e.

• A f t er le ukocy t es pa s s t hr ou g h, th e bas em en t m em b ra ne s be com e con ti nuou s a g a i n.

• Th e c e lls t ha t h av e e xi te d t he ves se l the n m ig rat e t owa rd th e ch em ota c ti c g radi e nt

crea t ed by c he m ok ine s an d ot her c he m oat tra ct an ts a nd ac c um ul a te in th e ext rava s cu la r
si te .

• The m ost te ll in g p roof of t he im p or ta nc e of leu koc y te a dh es ion m olec ul es in t he h os t

in fl am m a tor y r es pons e a re g ene ti c defi c ie nc ie s i n the s e m ol ecu le s, wh ic h res ul t in
in cr ea se d s us ce pti bil it y t o ba ct er ia l in fec ti ons.
CHEMOTAXIS OF LEUCOCYTES:
• Af ter exiting the circulation, leukocytes move in the tissues toward the site of injur y

by a process called CHEMOTAXIS .

• Both exogenous and endogenous substances act as chemoattractants.

• The most common exogenous factors are bacterial products, including peptides with

N-formylmethionine terminal amino acids and some lipids.

• Leukocytes migrate in the direction of locally produced chemoattractants emanating

from the site of the infl ammator y stimulus.

• En dog en ous c hem oa tt rac ta nt s: ( 1 ) c y t ok i ne s, pa r ti cul a rly t hose of th e c he m oki ne f am i ly
(e . g ., IL- 8 ) ;

( 2) com pon ent s of t he c om ple m en t sy st em , pa r ti cu l ar ly C5 a; an d

( 3) ara c hi donic a c id ( A A ) me ta boli te s, m a in ly le ukot ri ene B 4 ( LTB 4) .

• A ll t hes e ch em ota c ti c ag ent s bin d t o sp ec ifi c s even tran sm em b ran e G p rote in –c oupl ed
re ce ptor s on t he su r f ac e of leu koc y t es.

• Si gna ls i nit ia te d f rom the se r ece pt or s re sul t in a ct ivat ion of sec ond m es se ng e rs th at
in duc e poly m e ri z at ion of a c tin a t th e l ea di ng edg e of th e ce ll a nd loc al iz at ion of myos in
fi la m en ts a t the ba c k.
• Thi s r eorg an iz at ion of th e c y t oske le ton al lows th e l ea di ng edg e of th e le ukoc y t e to e xten d
fi lopodi a th at pu ll th e ba ck of t he ce ll in t he di re cti on of e xten si on, m u ch a s an
a utom obi le wit h f ront-wh eel dr ive i s pul led by t he wh ee ls in f ront .

• Th e n et r esu lt i s t ha t le ukoc y t es m i g rat e in th e dir ec ti on of loc al ly produ c ed

chem oa tt rac ta nt s em a na ti ng fr om th e si te of t he in fl am m a tor y s ti m ul us .
• The nature of the leukocyte infi ltrate varies with the age of the infl ammator y

response and the type of stimulus.

• In most forms of acute infl ammation, neutrophils predominate in the infl ammator y

infi ltrate during the fi rst 6 to 24 hours and are replaced by monocytes in 24 to 48

hours.

• Once leukocytes (par ticularly neutrophils and monocytes) are recruited to a site of
infection or cell death, they must be activated to per form their functions.

• The responses of these leukocytes consist of recognition of the off ending agents by
Toll like Receptors(TLRs) and other receptors, which deliver signals that activate the
leukocytes to phagocytose and destroy the off ending agents.
Phagocytosis and Clearance of the Offending Agent:

• The two major phagocytes are neutrophils and macrophages.

• Recognition of microbes or dead cells induces several responses in leukocytes that

are collectively called LEUKOCYTE ACTIVATION .

Phagocytosis involves sequential steps :

• Recognition and attachment of the particle to be ingested by the leukocyte;

• Engulfment, with subsequent formation of a phagocytic vacuole; and

• Killing of the microbe and degradation of the ingested material.

1. RECOGNITION AND ATTACHMENT:

• Pha g ocy tosi s is in it ia te d by th e expr ess ion of sur fa c e re cep tors on m a cr op ha g es wh ic h

re cog nis e m ic roorg a ni sm s :
• Mannose receptors
• Scavenger receptors
• Receptors for various
opsonins
• The pr oc e ss of p ha g ocy tosi s is fu r t he r e nh an ce d wh en th e m ic roorg a ni sm s a re c oat ed
wit h s pec i fi c p rote in s, ops onin s, from th e s er um or t he y g e t o psoni se d.

• Op soni ns es ta bl ish a bon d b etwe en ba ct er ia a nd th e ce ll m em bran e of ph ag oc y t ic c el l.

• The m a in opson ins pr es en t i n th e s er um an d t he ir c or re spond in g r ec ept ors on the s ur fa ce
of pha g ocy ti c ce lls (PM N s or m a c ropha g e s) ar e a s un der :

i ) Ig G op so nin is th e F c fra g m en t of im m un og lobu li n G; it i s t he n at ura ll y oc cu rri ng

a nti body in th e se rum th at c oat s t he ba c ter ia wh il e t he PM Ns pos ses s re ce ptors f or the
sa me.

i i) C3 b op s oni n is the f rag m ent g e ne rat ed by ac ti va ti on of c om ple m en t p at hway. It is

st rong ly ch em ota c tic for at tra ct in g PM N s to ba c te ria .

i ii ) Le ct i ns ar e ca rbohy drat e- bi nd ing pr ote ins i n t he pl as m a whic h bi nd to b ac te ria l c el l

wal l.
2. ENGULFMENT:
• The opson is ed pa r t ic le boun d t o t he su r f ac e of p ha g ocy te is r ead y to be e ng u lf ed.

• Th is is a c com pl ish ed by form a ti on of c y t op la smic pse udopods a roun d th e pa r ti cl e due to

a ct ivat ion of a c ti n fi l am e nt s b en eat h ce ll wal l, e nve lopin g it in a ph ag ocy t ic va cuol e.

• Eve nt ua ll y, the pl as m a m em bran e e nc los in g t he pa r t ic le br ea k s f rom t he c el l sur fa c e so

th at m e m bra ne li ned p ha g ocy t ic va cuol e or p ha g osom e li es in te rna l ise d a nd fr ee i n t he
cell c y topl a sm .

• Th e p ha g osom e fu se s wi th one or m ore ly sosom es of th e ce ll a nd form big g er vac u ol e

cal led p ha gol ys os om e .
3. KILLING AND DEGRADATION
• N e x t c o m e s t h e s t a g e o f k i l l i n g a n d d e g ra d a t i o n o f m i c r o o r g a n i s m t o d i s p o s e i t o ff j u s t i f y i n g t h e
f u n c t i o n o f p h a g o c y t e s a s s c a va n g e r c e l l s .

• T h e m i c r o o r g a n i s m s a f t e r b e i n g k i l l e d b y a n t i b a c t e r i a l s u b s t a n c e s a r e d e g ra d e d b y h y d r o l y t i c
e n z y m e s . H o w e v e r, t h i s m e c h a n i s m f a i l s t o k i l l a n d d e g ra d e s o m e b a c t e r i a l i k e t u b e r c l e b a c i l l i .

• Disposal of microorganisms can proceed by following mechanisms:

A . I n t ra c e l l u l a r m e c h a n i s m s : i ) O x i d a t i v e b a c t e r i c i d a l m e c h a n i s m b y o x y g e n f r e e ra d i c a l s

a) Myeloperoxidase - dependent

b) Myeloperoxidase - independent

ii) Oxidative bactericidal mechanism by lysosomal granules

iii) Non-oxidative bactericidal mechanism

B . E x t ra c e l l u l a r m e c h a n i s m s .
Intracellular mechanisms:
I ) OXI DAT I VE B ACT ER ICI DAL ME CH A NI SM BY OXYGE N FR EE R ADICA LS

• A n im p or ta nt m e ch an is m of m ic robi ci da l k i ll ing is by oxida ti ve dam a g e by th e produ c tion

of rea c ti ve oxyg e n m e ta boli te s ( O’ 2 H 2O2 , OH ’, H OC l, HOI, HOB r) .

• A pha s e of i ncr ea se d oxyg e n c ons um pt ion ( ‘r es pira tor y b ur st ’) by a c tiva te d ph ag ocy t ic

le ucocy t es r equ ir es th e e ss en tia l pre se nc e of N A D PH oxid as e.

• N A DPH - oxi da se pr ese nt in t he c ell m e m bra ne of pha g osom e re du ce s oxyg e n t o s uper ox ide
ion ( O’2 ) .
• Supe roxide is sub seq ue ntl y c onver t ed int o H ₂O₂ wh ic h h a s bac te ri ci dal pr oper t ies :

• Thi s t y pe of ba ct eri ci da l ac t iv it y i s ca rr ie d ou t e it he r v ia e nz y m e my elop eroxida s e ( M PO)

pr ese nt in t he a zu roph ili c g ra nu le s of ne ut roph il s a nd m onoc y te s, or i nde pen den t o f
en zy m e MPO, a s und er :

a ) M ye loper oxi da se - de pe nde nt

b ) M yel operoxid as e - i nde pe nde nt

a) MPO-dependent killing:
• In th is m ec h an ism , th e e nz y m e M PO ac t s on H ₂O₂ i n the pr es en ce of ha li des ( c hl orid e,
iodi de or b rom id e) t o f or m hy poha lous ac id ( HOC l , H OI, HO Br ) .

• Th is is c a lle d H 2 O2- M PO- ha li de sy ste m a nd is m or e p ot en t an tib ac te ri al s y st em i n

poly m or phs t ha n H2 O2 a lone :
b) MPO-independent killing:
• M at ur e m ac roph ag es la ck th e e nz y m e M PO a nd th ey ca rr y ou t bac t eri ci da l ac ti v it y b y
pr od uc in g OH ‾ ions a nd su pe roxi de si ng let oxygen ( O’ ) fr om H ₂O₂ i n the pr es enc e of O’ ₂
( Ha b er-Wei s s r e a ct io n ) or in th e pre se nc e of Fe++ ( Fe nton r ea c ti on ) :

• Re a ct ive oxyg e n m et ab ol it es a re pa r t ic ul ar ly us efu l in e lim i na ti ng m ic robi al org an ism s

th at g r ow wit hin p ha g ocy tes e .g . M . tu be rcu los is, Hi st op la sm a c a psu lat um .
ii) Oxidative bactericidal mechanism by lysosomal granule:

• In th is m ec h an ism , th e p ref orm e d g ra nu le - stor ed pr od uct s of neu tr ophi ls a nd

ma cr op ha g es a re di sc ha rg ed or s ec re ted in to the ph ag osom e an d t he ext rac e llu la r
env ir on m en t.

• Wh il e the r ole of MPO i s al re ad y h ig h lig ht ed above, oth ers l ibe rat ed by deg ra n ul at ion of
ma cr op ha g es a nd ne ut rophi ls a re pr otea se , tr y p sin a se, phos pholi pa se , an d a l ka li ne
ph os pha ta s e.

• Pr og res si ve deg ran ula ti on of n eu troph il s a nd m a c ropha g e s al on g wi th oxy g en fr ee

ra dic a ls deg rade s prot ei ns i. e. in duc es pr ot eol y si s.
iii) Non-oxidative bactericidal mechanism:
• Som e a g e nt s r el ea se d f rom t he g ra nu le s of ph ag oc y t ic c el ls do n ot req uir e oxyg e n f or
ba ct er ic ida l ac t iv it y.

• The se in cl ud e t he fol lowin g :

a ) Gra nul es : Som e of l ibe rat ed ly s os om al g ran ule s do n ot k i ll by oxi dat ive da m a g e but
cau se ly sis of wit hin p ha g osom e. Th es e a r e l y sos om al hyd rola se s, pe rm e ab il ity in c rea si ng
fa ctors , c at ioni c prot ein s ( def en sin s) , li pas es , pr ot ea se s, D N A as es .

b ) Ni tr i c oxi de : N it ri c oxid e r ea c tiv e f re e ra di ca ls s im il a r to oxyg en fr ee ra di ca ls a re

for med by nit ri c oxi de sy n th as e a nd i s a p ot en t m ec ha ni sm of m i cr ob ia l ki ll in g . N it ric oxide
is pr oduc ed by en dothe l ial c el ls a s we ll a s by ac ti va ted m a c ropha g e s.
B. EXTRACELLULAR MECHANISMS:
• Fol lowin g m ec ha ni sm s expl ai n th e ba c te ric id al a ct iv i ty a t extra ce ll ula r l evel :

i ) G ra nul es : D eg ran ul at ion of m a c roph ag e s an d neu troph il s expl ai ned a bove c ont in ues t o
exer t it s e ff ec ts of prot eoly sis ou tsi de th e ce lls a s well .

i i) Imm une me c hani s m s : Im m u ne -m e dia te d ly s is of m ic robe s t ake s p la ce out si de th e

cell s by m ec ha ni sm s of c y t oly s is, an ti body- m e di at ed ly sis a nd by ce ll - m edi at ed cy totoxic it y
The Actions of the Principal Mediators of Infl ammation:
CELL-DERIVED MEDIATORS:
MEDIATORS PRINCIPAL SOURCES ACTIONS

HISTAMINE Mast cells, basophils, platelets Vasodilation, increased vascular

permeability, endothelial activation
SERATONIN Platelets Vasodilation, increased vascular permeability

PGs Mast cells, leucocytes Vasodilation, pain, fever

LTs Mast cells, leucocytes increased vascular permeability,

chemotaxis, leucocyte adhesion and
activation
PAF Mast cells, leucocytes increased vascular permeability, chemotaxis,
leucocyte adhesion, degranulation, oxidative
burst

ROS leucocytes Killing of microbes, tissue damage

NO Endothelium, macrophages Killing of microbes, vascular smooth muscle

relaxation
CYTOKINES(TNF,IL-1) Macrophages, endothelial cells, mast Local endothelial activation,
cells fever/pain/anorexia/hypotension,
decre. Vascular resistance
CHEMOKINES Leucocytes, activated macrophages Chemotaxis, leucocyte activation
PLASMA-PROTEIN DERIVED:
MEDIATORS PRINCIPAL SOURCES ACTIONS
COMPLEMENT PLASMA(produced in liver) Leucocyte chemotaxis , activation
PRODUCTS(C5a,C3a,C4a) and vasodilation(mast cell
stimulation)
KININS PLASMA(produced in liver) vascular permeability, smooth
muscle cell contraction,
vasodilation, pain
PROTEASE ACTIVATED PLASMA(produced in liver) Endothelial activation, leucocyte
DURING COAGULATION recruitment
CHRONIC INFLAMMATION:
• C h r o n i c i n fl a m m a ti o n i s a r e s p o n s e of p r o l o n g e d d u ra t i o n ( w e e k s o r m o n t h s ) i n w h i c h
i n fl a m m a t i o n , t i s s u e i n j u r y a n d a t t e m p t s a t r e p a i r c o e x i s t , i n va r y i n g c o m b i n a t i o n s .

• I t m ay f o l l o w a c u t e i n fl a m m a t i o n , or c h r o n i c i n fl a m m a t i on m a y b e g i n i n s i d i ou s l y, a s a l ow -
g r a d e , s m o l d e r i n g r e s p o n s e w i t h ou t a n y m a n i f e s t a t i o n s o f a p r e c e d i n g a c u t e r e a c t i o n .

M O R P H O LO G I C F E ATU R E S :

C h r o n i c i n fl a m m a t i o n i s c h a ra c t e r i z e d b y :

• I n fi l t ra t i o n w i t h m o n o n u c l e a r c e l l s , w h i c h i n c l u d e m a c r o p h a g e s , l y m p h o c y t e s , a n d p l a s m a
cells

• T i s s u e d e s t r u c t i o n , i n d u c e d b y t h e p e r s i s t e n t o ff e n d i n g a g e n t o r b y t h e i n fl a m m a t o r y c e l l s

• At t e m p t s a t h e a l i n g b y c o n n e c t i ve t i s s u e r e p l a c e m e n t o f d a m a g e d t i s s u e , a c c o m p l i s h e d b y
a n g i o g e n e s i s ( p r o l i f e r a t i o n o f s m a l l b l o o d ve s s e l s ) a n d , i n p a r t i c u l a r, fi b r o s i s .
CELLS AND MEDIATORS OF CHRONIC INFLAMMATION:
Macrophages

• The dominant cells in most chronic infl ammator y reactions are macrophages, 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, notably T lymphocytes.

• Macrophages are professional phagocytes that act as fi lters for par ticulate matter,
microbes, and senescent cells.

• They also function as eff ector cells that eliminate microbes in cellular and humoral
immune responses.

• There are two major pathways of macrophage activation, called classical and
alternative
 Lymphocytes:

• Microbes and other environmental antigens activate T and B lymphocytes, which

amplify and propagate chronic infl ammation.

• Although the major function of these lymphocytes is as the mediators of adaptive

immunity, which provides defense against infectious pathogens , these cells are of ten
present in chronic infl ammation and when they are activated, the infl ammation tends
to be persistent and severe.
Granulomatous Infl ammation:
• This distinctive form of chronic infl ammation is characterized by focal accumulations
of activated macrophages (granulomas); macrophage activation is refl ected by
enlargement and fl attening of the cells (so-called epithelioid macrophages).

• Nodules of epithelioid macrophages in granulomatous infl ammation are surrounded

by a collar of lymphocytes elaborating factors necessar y to induce macrophage
activation.

• Activated macrophages may fuse to form multinucleated giant cells, and central
necrosis may be present in some granulomas (par ticularly from infectious causes).

• Older granulomas can be surrounded by a rim of fi brosis.

• Foreign body granulomas are incited by par ticles that cannot be readily phagocytosed
by a single macrophage but do not elicit a specifi c immune response (e.g., suture or
talc).

• Immune granulomas are formed by immune T cell-mediated responses to persistent,

poorly degradable antigens.

• IFN-γ from activated T cells causes the macrophage transformation to epithelioid

cells and the formation of multinucleated giant cells.

• The prototypical immune granuloma is caused by the tuberculosis bacillus; in that

setting the granuloma is called a tubercle and classically exhibits central caseous
necrosis.
• Granulomatous infl ammation is a distinctive infl ammator y reaction with relatively
few possible causes.

• Infectious aetiologies: Tuberculosis, leprosy, syphilis, cat-scratch

disease, schistosomiasis, cer tain fungal infections

• Infl ammator y causes: Temporal ar teritis, Crohn disease, sarcoidosis

• Inorganic par ticulates: Silicosis, ber ylliosis

SYSTEMIC EFFECTS OF INFLAMMATION:
• Infl ammatio n, even i f i t i s l ocal ized, i s associ ated wi th cytok ine- induced systemi c
reaction s that are co ll ecti vel y cal l ed the acute- phase r esponse .

• Fever, ch aracteri zed by an elevati on o f body temperature, usual l y by 1° to 4°C , i s one

o f the mo st promi nent mani festa ti on s o f the acu te- phase response, especial l y wh en
i nfl ammatio n is associ ated wi th infecti o n.

• Acu te-ph ase proteins are pla sma pro tei ns, mostly synthesized in the li ver, who se
pl asma con centrati ons may i ncrease several hundred-fol d as par t o f the response to
i nfl ammator y sti muli .

• Leukocy tosis is a commo n feature of infl amma to r y reactio ns, especi al ly th ose i nduced
by bacteri al i nfecti ons. Th e l eukocyte cou nt usual l y cl imbs to 15,00 0 o r 20,000
cel ls /mL, bu t so meti mes it may reach ex traordinaril y high level s o f 40 ,0 00 to 1 00, 00 0
cel ls /mL. These ex treme elevati ons are referred to a s leukemoid r eactions.
• Other manifestations of the acute-phase response include increased pulse and blood
pressure; decreased sweating, mainly because of redirection of blood fl ow from
cutaneous to deep vascular beds, to minimize heat loss through the skin; rigors
(shivering), chills (search for warmth), anorexia, somnolence, and malaise, probably
because of the actions of cytokines on brain cells.
APPLIED ASPECTS:
• There are many diseases in which the infl ammator y reaction is misdirected (e.g.,
against self tissues in autoimmune diseases), occurs against normally harmless
environmental substances (e.g., in allergies), or is inadequately controlled.

• In these cases, the normally protective infl ammator y reaction becomes the cause of
the disease, and the damage it causes is the dominant feature.
INFLAMMATION OF ORAL TISSUES:
• SOF T TISSUES • HARD TISSUES

PULPITIS ALVEOLAR OSTEITIS

OSTEOMYELITIS
PERIODONTIT IS
ARTHRITIS
RECURRENT APHTHOUS ULCER

ORAL LICHEN PLANUS

ORAL SUBMUCOUS FIBROSIS

ORAL CANCER
PULP INFLAMMATION:
 ORAL LICHEN PLANUS:

Endothelium
Basal
upregulates Lymphocytes(T
keratinocytes
Langerhans cells adhesion cells) recruited to HYPERKERATOSIS
neoexpress and
Antigenic and factor VIII-A molecules(e.g.,IC and retained in (Reduced
lymphocytes
stimulation(exoge dendrocytes AM and ECAM) submucosa(throu keratinocyte
attach through
nous increase(associate (induced by gh receptors to desquamation due
lymphocyte
/endogenous) d with antigenic resident endothelial to enhanced
receptors to ICAM
challenge) macrophages, adhesion membrane
and undergo
Langerhans cells, molecules) adhesion)
apoptosis
dendrocytes)
ORAL SUBMUCOUS FIBROSIS:

CONSTANT
ORAL MUCOSA BETEL QUID HABIT
IRRITATION

DURATION
SUSCEPTIBILITY DUE &FREQUENCY OF THE
TO Fe+ & Vit B12 HABIT

CHRONIC
INFLAMMATION

ACTIVATED T-CELL &

IL-6,TNF,IF-α,TGF-β
MACROPHAGES
OSTEOMYELITIS:
• It is de fi ned a s an in fl am m a ti on of m a rr ow spa c es of bone with t en den cy of involv em en t
of cor ti ca l pla te s an d pe ri oste um .

• Et io lo gy:

D en ta l inf ec ti on

• Cl in ic a l fe at ur es :

Seve re pa in , t ri sm us , par es th esi a of l ip

El evat ion of tem p era tu re

Reg i ona l l y m ph ade nopa thy

Pus exu da te th roug h g in g ival p oc kets

REFERENCES:
• ROBB INS A ND C OTRA N PATH OLOG ICA L B ASIS OF D ISEASE ., 10 t h ED ITION.

• H A RSH M OH A N -TEX TB OOK OF PATHO LOGY., 6 t h ED ITION .

• SHA F ERS TE XTB OOK OF ORA L PATRHOLOGY., 7 t h E D ITION .

• BURK ITS TEX TBO OK OF ORA L M ED IC INE

• INTE RNET SOURC E

THANKYOU
FOR YOUR
ATTENTION!