Chronic Inflammation

•
Chronic
inflammation is a
response of prolonged
duration ( weeks or months) in which
inflammation ,

tissue
injury and
attempts at repair coexist .
in
varying
combinations .

Causes of CI :

in
Infection in the most common cause
of CI .

Tuberculosis
As -

,
leprosy ,
hepatitis C

Iii , Autoimmune disease . As -

Rheumatoid Arthritis ,
Lupus
sterile
iii.
Inflammatory reaction to
agents
As - Silica ,
Uric acid
,
silicone in breast implants .

toxic
in
Prolonged exposure
to
potentially agents ,
either

exogenous
or
endogenous .

Morphology of CI :

(1) Cell
types that define CI :

(a)
Monocytes and Macrophages ( key cells )
(b)
Lymphocytes ,
Plasma cells &
Eosinophils

fig :

chronic Inflammation
showing
•

lymphocytes
•
Plasma cells
 Destruction Tissue ( Parenchyma )
(2) of -
with loss
of
parenchyma ,
there in loss
of functional tissue ,
with

repair by fibrosis .

(3) Formation of Granulation tissue .

vascular tissue composed of blood vessels

Highly
activated
and
fibroblasts .

Vascularization
-
is normal
for wound
healing .

Angiogenesis takes place .

Granulation tissue is
precursor of Scar tissue .

Tig :
Granulation Tissue

( Mixture
og Acute [ Neutrophils]
and chronic
inflammatory
cells [ lymphocytes Plasma .

Cells ,
Macrophages ]
intermixed with small
vessels )

Cells & Mediators of CI

1- .

Macrophages :

•
Dominant cells in most CI reactions are
macrophages .

Contribute to reaction
the
by secreting cytokines and
•

growth factors .
 • Activates T
lymphocytes .

Macrophages tissue cells derived

from hematopoietic
°

are

stem cells in bone marrow and from progenitors in

the
embryonic
yolk sac and
fetal liver
during
early development .

→€ .

There two activation

•
are
major pathways of macrophage .

called ( is classical and

eii,
Alternative .

stimuli that activate

-
The
macrophages by these

pathways functions of
,
and Activated cells ,
are

quite different .
 Products of Activated eliminate injurious
macrophages
•

agents such as microbes and initiate the

process of Repair
much
but also
responsible for of tissue
injury in CI .

Functions :

tissues
"i
Ingest & Eliminate microbes and dead .

( iii Initiate Tissue Repair and involved in scar

formation
and fibrosis .

secrete mediators
of inflammation
such
Ciii ,
Macrophages ,
as

cytokines ( TNF ,
Il -
L ,
chemokines ,
and others ) &

eicosanoids .

1in
Display Antigens to T
lymphocytes and respond to
signals
from T cells ,
thus
setting up feedback loop .
 2. T
lymphocytes :

°
Produced in Bone Marrow as
progenitor T cells .

•
Further
develop thymus where T cell receptor ( )
in TCR

undergoes rearrangement and becomes helper 7 cells

+
a> 4

cytotoxic T cells
+
or CDs .

• TCR
complex recognizes antigen presented on Mnc molecules :

( is CD 4+7 cells - MHC Class I

+
Iii , CDs T cells -
Mnc Clan I

Activation
of T cells
requires Binding of Antigen / Mnc Comp
•
in .

(2) An additional 2nd signal .

subsets that secrete

There 3
of different
•

are CDG -1 T cells

types of cytokines and elicit different types of inflamma

-
lion .

cis Tnt cells produce cytokine IFN -

y ,
which activates

macrophages by classical
pathway .

Iii ' Th 2 cells secrete Il 4 -

,
I L -5 & Il -
13
,
which

recruit and activate eosinophils and are

responsible for the alternative pathway y

macrophage activation .

Ciii) secrete which

7h17 cells II -17 and other
cytokines ,

induce the secretion chemokines responsible for

of
recruiting neutrophils ( &
Monocytes ) into reaction .
 3. B
lymphocytes :

•
Immature B cells are
produced in bone marrow and

undergo immunoglobulin rearrangements to become

B cells that express surface IgM

&
IGD
.

•
B cells activation occurs via :

Antigen binding by surface IgM IGD : results in

-

or

maturation to
IgM or
IGD secreting plasma cells
-
-
.

antigen presentation to +
B 7 cells
cells CDG
helper via
•

MHC class I -

• CD 40
Receptor on B cells binds CDGOL on
helper T-cell ,

providing
and Activation signal .

Helper T cells then secrete II -4 & IL -5

( mediate
B. cells to Plasma cells )
 Granulomatous Inflammation
•

Specialized / Subtype og chronic

inflammation .

Causes

cis
Infections :

la '
Fxamples TB and
systemic fungal infection
-

(b) Infections caused

by TB & Systemic fungi are

associated
usually with caseous necrosis .

Lii ,
Noninfectious Causes :

(a) Examples - Sarcoidosis and Crohn Disease

(b) Sarcoidosis and Crohn disease have non

caseating
granulomas .
 Morphology of Granuloma
•
Pale ,
white nodule with or without central caseation .

Usually well -
circumscribed in tissue .

Fig : Non -

necrotizing
Granuloma in a

lymph Mode in

the Neck .

Formation
of Granuloma
:

in
Macrophages process
and
present antigen via Mnc

class to -1
I CDG
helper T cells .

Interaction leads to secrete

(2)
macrophages II -12
,

including CDG
-1
Helper T cells to differentiate into

Tnt subtype .

Tnt secrete which converts

(3) cells IFN
y macrophages
-

to epithelioid histiocytes and giant cells .

-
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