Outcomes of Acute Inflammation: - PowerPoint Presentation

Slide1

Outcomes of Acute

Inflammation:

1-Resolution:

restoration

to

histologic

and

functional

normalcy

:

-

Neutralization

or

removal

of the various

chemical mediator

s

.

-

N

ormalization

of vascular

permeability

, and

cessation

of

leukocyte

emigration

with subsequent

death

(by

apoptosis

) of

extravasated

neutrophils

.

-Lymphatic drainage

and

macrophage

ingestion of

necrotic

debris and clearance

of the

edema

fluid

,

inflammatory

cells

at the site of inflammation.

2-Scarring or fibrosis:

-

Occurred

in case of

substantial

tissue

destruction

or in tissues that do not

regenerate

. extensive

fibrinous

exudates (due to increased vascular

permeability

) may not be completely

absorbed

and are

organized

by

ingrowth

of

connective tissue

with resultant

fibrosis

.

In

abscess

,

because of

extensive

underlying tissue

destruction,

the

only outcome

is

scarring

.

3-Progression to chronic inflammation

may

follow

acute inflammation, although

signs

of

chronic

inflammation may be

present

at the

onset

of injury (e.g. in

viral

infections or

immune responses

to

self-antigens

).

CHRONIC INFLAMMATION

prolonged duration

(

weeks

to

months

to

years

) in which

active

inflammation, tissue

injury

, and

healing

proceed simultaneously.

influx

of

lymphocytes

and

macrophages

with associated

vascular proliferation

and

scarring

.

Slide2

Cauases

of chronic inflammation:

1-Viral infections.

2-Persistent microbial infections.

-

Mycobacteria

(

tubercle bacilli

),

Treponema

pallidum

(causative organism of

syphilis

), and certain

fungi

.

evoke

an immune response called

delayed hypersensitivity (

granulomatous

reaction)

.

3-Prolonged exposure to potentially toxic agents

.

-Exogenous

nondegradable

material such as

Inhaled

particulate silica

, which can induce (

silicosis

) in the

lungs.

-Endogenous

agents such as

chronically elevated plasma lipid components

, which may contribute to

atherosclerosis

.

4-Autoimmune diseases.

-

Immune

response to

self-antigens

and

tissues

. (e.g.,

rheumatoid arthritis

or multiple

sclerosis

).

Chronic inflammatory Cells and Mediators

1-Macrophages

-

(

mononuclear phagocyte system) in different organs.

-Filters

for

particulate matter

,

microbes

, and

senescent

cells.

-Sentinels

to alert the specific

components

of the immune system (

T and B

lymphocytes) to

injurious stimuli.

-Emigrate

to the site of injury within the

first 24 to 48

hours after

onset

of

acute

inflammation.

-Activated

by bacterial

endotoxin

,

cytokines

secreted by

sensitized

T lymphocytes

(

IFN-γ

),

mediators

of

acute

inflammation, and

extracellular

matrix proteins such as

fibronectin

.

-After activation

undergo

transformation

into the

large

,

flat

, and

pink (

epithelioid

macrophages)

.

-

IL-4 or IFN-γ (

from lymphocytes

)

can also induce macrophages to

fuse

into

large

,

multinucleated

cells called

giant cells

.

Slide3

Events in the

resolution

of inflammation

Slide4

Macrophage products include

:

-Proteases,

plasminogen activator.

-Complement components.

-Reactive oxygen species and nitric oxide.

-AA metabolites

(

eicosanoids

).

-Cytokines

, such as

IL-1

and

TNF

, as well as a variety of

growth factors (PDGF)Platelet-derived

growth factor ,

(FGF)

fibroblast growth factors, Transforming growth factor

beta (TGF-beta)

that influence the proliferation of

smooth muscle cells

and

fibroblasts

and the production of extracellular matrix (as

collagen

).

2-Lymphocytes

-

Both

T

and

B

lymphocytes

migrate

into inflammatory sites.

-

T lymphocytes

have a

reciprocal

relationship to

macrophages

in chronic inflammation; they are

initially

activated

by interaction with

macrophages presenting "processed" antigen fragments

on their

cell surface

. The activated lymphocytes then

produce

a variety of mediators, including (

IFN-γ)

, a

major

stimulating

cytokine

for activating (

monocytes

and

macrophages).

Activated

macrophages

in turn

release cytokines, including (

IL-12

,

IL-1

and

TNF)

, that further activate (

lymphocytes)

as well as other cell types.

3-Eosinophils

-Present

in inflammatory sites around

parasitic

infections or as part of immune reactions mediated by

IgE

, typically associated with

allergies

.

-Recruited

chemokines

(e.g.,

eotaxin

) derived from

leukocytes

or

epithelial

cells.

-

Eosinophil

-specific

granule

s contain

major basic protein

(

MBP

), that is

toxic

to

parasites

but also causes

epithelial cell

lysis

.

Slide5

4-Plasma Cells

-product

of

B-cell

activation.

-produce different Abs(

immunoglobulins

).

5-Mast Cells

-Sentinel

cells in

connective

tissues throughout the

body.

-participate

in both

acute

and

chronic

inflammatory responses.

-Release

histamines

and

AA

metabolites.

-Elaborate

cytokines such as

TNF

, thereby participating in

more chronic

responses.

-play

a role in

parasitic infections

.

Fibroblast

-Activated

by

macrophages

growth factors (

PDGF

,

FGF

,

TGF-beta

).

-Produce of

ECM

(as

collagen

).

-

PDGF = p

latelet

D

erived

G

rowth

F

actor.

FGF = F

ibroblast

G

rowth

F

actor

.

TGF-beta = T

ransforming

G

rowth

F

actor

.

Slide6

The

roles of activated macrophages

in chronic inflammation. Macrophages are activated by

nonimmunologic

stimuli such as

bacterial

endotoxin

or by

cytokines

from immune-activated

T

cells, particularly

(

IFN-gamma

;). The products made by activated macrophages that cause tissue injury and fibrosis are indicated.

AA

,

Arachidonic

acid;

PDGF

, platelet-derived growth factor;

FGF

, fibroblast growth factor;

TGF-beta

;, transforming growth factor

beta.

Slide7

Macrophage-lymphocyte

interactions in chronic inflammation.

Activated lymphocytes

and

macrophages

stimulate each other, and both cell types release inflammatory

mediators

that affect other cells.

IFN

-gamma

;,

interferon-gamma;

IL-1

,

interleukin-1

;

TNF

, tumor necrosis factor.

Slide8

Thickenning

of alveolar septa (Fibrosis)

Empty alveolar spaces

Chronic Pneumonia

Slide9

Chronic Pneumonia

Slide10

Lymphocytes

Chronic Pneumonia

Slide11

Chronic Pneumonia

Slide12

Chronic Pneumonia

Alveolar spaces with overfilled

macrophages

Slide13

Chronic Pneumonia

Alveolar spaces with overfilled

macrophages

Slide14

Chronic pneumonia

Massive fibrosis with inflammatory cells

Slide15

Massive infiltration of lymphocytes

Newly formed Blood vessels

Chronic pneumonia

Slide16

Chronic myocardial infarction

Necrotized myocardial cell

Fibroblasts

Slide17

Slide18

Chronic myocardial infarction associated with angiogenesis (arrows)

Slide19

Slide20

Granulomatous

inflammation (

Granuloma

)

Granulomatous

inflammation is a

distinctive

pattern of

chronic

inflammation characterized by

aggregate

s of

activated macrophages

that assume a

squamous

cell-like (

epithelioid

) appearance

.

Result from

persistent T

-cell

responses to certain

microbes

or

foreign body

such as:

-Bacteria

(

Mycobacterium

tuberculosis

,

Treponema

pallidum

causing the

syphilitic

gumma

).

-Fungi.

-parasites.

-Inert foreign

bodies (e.g.,

suture

,

splinter

,

breast implant

) these types called (

foreign body

granulomas

).

Tuberculosis

is the

archetypal

granulomatous

disease

due to

infection,

where T-cell-derived

cytokines

are responsible for persistent

macrophage

activation.

Slide21

Component of

granuloma

:

1-Central

zone

of

necrosis (

caseous

necrosis).

2-Aggregates

of

epithelioid

macrophages.

3-Activated

macrophages

.

4-Collar

of lymphocytes secreting

the cytokines responsible for

ongoing

macrophage activation.

5-Older

granulomas

surrounded by

rim

of

fibroblasts

and

connective tissue.

6-Multinucleated

giant

cells

40 to 50

μm

in diameter:

large mass

of cytoplasm and

multiple nuclei

and derive from the

fusion of 20

or

more macrophages.

Slide22

Langhans

type (

multinucleated

giant cell) - Tuberculosis

Slide23

Foreign body type giant cell

s

Slide24

Grossly

, a

granuloma

(arrow) tends to be a focal lesion. Seen here in a

hilar

lymp

node is a

granuloma

.

Granulomas

due to infection are often "

caseating

" because they have prominent

caseous

necrosis.

Slide25

Langhans

giant cell

Granuloma

Slide26

Lung :

Granuloma

Central caseous necrosis

Langhans gaint cell

Slide27

Lung :

Granuloma

Lymphocytes

Epithelioid cells