INFLAMMASI -2

NUNUK PURWANTI
BIOMEDIKA KEDOKTERAN GIGI
INFLAMASI AKUT
• A hallmark of acute inflammation is increased vascular
permeability

•
leading to the escape of a protein –rich fluid (excudate) into the
extravascular tissue
Vascular Leakage
Increased Vascular Permeability
(rat cremaster muscle examined under transillumination)

One hour before saccrifice bradykinin was injected over this muscle,
and colloidal carbon was injected intravenously.
Leukocytes Rolling Within a Venule
Neutrophil Pavementing (lining the venule)
Neutrophil Transendothelial Migration (Diapedesis)
Ultrasructure and contents of netrophil
granules (stained for peroxidase activity)
General principles of the chemical mediators:

1. Mediators originate either from plasma or from cells.

2. The production of active mediators is triggered by microbial
products or by host proteins, such as the proteins of the
complement, kinin, and coagulation systems, that are themselves
activated by microbes and damaged tissues
3. binding to specific receptors on target cells.
4. One mediator can stimulate the release of other mediators by
target cells themselves.
5. Mediators can act on one or few target cell types, have diverse
targets, or may even have differing effects on different types of
cells.
6. Once activated and released from the cell, most of these mediators
are short-lived.
7. Most mediators have the potential to cause harmful effects.
Anti inflammation drug
Corticosteroids are widely used to suppress tissue destruction
associated with many inflammatory diseases, including allergic
responses, rheumatoid arthritis, and systemic lupus erythematosus.
Corticosteroids induce. Although corticosteroids (e.g., prednisone
synthesis of an inhibitor of PLA2 release of arachidonic acid in
inflammatory and block cells) are widely used to suppress
inflammatory responses, their prolonged administration can have
significant harmful effects, including increased risk of infection,
damage to connective tissue, and adrenal gland atrophy.
Inhibition of COX is one mechanism by which non-steroidal anti
inflammatory drugs (NSAIDs), including aspirin, indomethacin, and
ibuprofen, exert their potent analgesic and antiinflammatory effects.
NSAIDS block COX-2“induced formation of prostaglandins, thereby
mitigating pain and inflammation. However, they also affect COX-1,
lead to decreased homeostatic functions, and so affect the stomach
and kidneys adversely. This complication led to development of
COX-2“specific inhibitors.
 RADANGAKUT ►►► EKSUDATIF

Sub akut
Sub kronis

RADANG KRONIK ►►► PROLIFERATIF

Limfosit
Makrofag

SUMSUM DARAH JARINGAN

TULANG
STEM  MONO  MONOSIT  MAKROFAG  ACTIVATED MAKROFAG
SEL BLAS
-SEL EPITELOID
- SEL RAKSASA
MIKROGLIA, SEL KUPFFER, MAKROFAG ALVEOLUS (PARU)
 Events in the
resolution of
inflammation

1. Return to normal vascular

permeability
2. Drainage of the edema fluid and
proteins into lymphatics or
3. By pinocytosis into macrophages
4. Phagocytosis of apoptotic
neutrophils and
5. Phagocytosis of necrosis debris,
and
6. Disposal of macrophages
 1

2
3
Outcomes of accute inflammation
Schematic & Histologic Events Following Acute Injury (myocardium)

Early (neutrophilic) cellular infiltrates Later (mononuclear) infiltrates

Chronic Inflammation

chronic inflammation is considered to be inflammation

of prolonged duration (weeks or months) in which active
inflammation, tissue destruction, and attempts at repair
are proceeding simultaneously.
CAUSES OF CHRONIC INFLAMMATION
1. Persistent infections by certain microorganisms.
These organisms are of low toxicity and evoke an immune
reaction called delayed type hypersensitivity. The
inflammatory response sometimes takes a specific pattern
called a granulomatous reaction.
2. Prolonged exposure to potentially toxic agents, either
exogenous or endogenous.
3. Autoimmunity
Immune reactions develop against the individual's own
tissues, leading to autoimmune diseases.
MORPHOLOGIC FEATURES

chronic inflammation is characterized by:

1. Infiltration with mononuclear cells, which include
macrophages, lymphocytes, and plasma cells.
2. Tissue destruction, induced by the persistent
offending agent or by the inflammatory cells.
3. Attempts at healing by connective tissue
replacement of damaged tissue, accomplished by
proliferation of small blood vessels (angiogenesis)
and, in particular, fibrosis. 
Macrophage is the dominant cellular player in chronic inflammation.
Macrophages are one component of the mononuclear phagocyte
system
Activated macrophages
secrete a wide variety of
biologically active
products that, if
unchecked, result in the
tissue injury and fibrosis
characteristic of chronic
inflammation
In chronic inflammation, macrophage accumulation
persists, and is mediated by different mechanisms:
1. Recruitment of monocytes from the circulation.
2. Local proliferation of macrophages
3. Immobilization of macrophages within the site of
inflammation.
Mechanisms of
macrophage
accumulation
in tissues.
A, Chronic inflammation in the lung, showing all three characteristic histologic
features: (1) collection of chronic inflammatory cells (*), (2) destruction of parenchyma
(normal alveoli are replaced by spaces lined by cuboidal epithelium, arrowheads), and
(3) replacement by connective tissue (fibrosis, arrows). B, By contrast, in acute
inflammation of the lung (acute bronchopneumonia), neutrophils fill the alveolar
spaces and blood vessels are congested.
Langhans giant cell
Foreign body giant cell
The products of activated macrophages serve to
eliminate injurious agents such as microbes and to
initiate the process of repair, and are responsible for
much of the tissue injury in chronic inflammation.

Tissue destruction is one of the hallmarks of chronic

inflammation.
OTHER CELLS IN CHRONIC
INFLAMMATION
Lymphocytes.
mobilized in both antibody-mediated and cell-
mediated immune reactions and even in non immune
inflammation. Lymphocytes and macrophages interact
in a bidirectional way. Macrophages display antigens to
T cells, and produce membrane molecules
(costimulators) and cytokines (notably IL-12) that
stimulate T-cell responses. Activated T lymphocytes
produce cytokines, and one of these, IFN-γ, is a major
activator of macrophages.
Eosinophils
abundant in immune reactions mediated by and in
IgE parasitic infections. Eosinophils have granules
that contain major basic protein, a highly cationic
protein that is toxic to parasites but also causes lysis
of mammalian epithelial cells.
Mast cells
widely distributed in connective tissues and participate in
both acute and persistent inflammatory reactions. Mast
cells express on their surface the receptor that binds the
Fc portion of IgE antibody (FcεRI).

Although neutrophils are characteristic of acute

inflammation, many forms of chronic inflammation, lasting
for months, continue to show large numbers of neutrophils,
induced either by persistent microbes or by mediators
produced by macrophages and T lymphocytes.
Granulomatous inflammation
Granulomatous inflammation is a distinctive pattern of
chronic inflammatory reaction characterized by focal
accumulations of activated macrophages, which often
develop an epithelial-like (epithelioid) appearance.

A granuloma is a focus of chronic inflammation

consisting of a microscopic aggregation of
macrophages that are transformed into epithelium-like
cells surrounded by a collar of mononuclear leukocytes,
principally lymphocytes and occasionally plasma cells.
Granulomatous inflammation
Mechanism of granuloma
formation
LYMPHATICS IN INFLAMMATION

Together with the mononuclear phagocyte system, it represents a secondary

line of defense that is called into play whenever a local inflammatory reaction
fails to contain and neutralize an external agent, such as a microbe.
The drainage may transport the offending agent, be it chemical or microbial.
The lymphatics may become secondarily inflamed (lymphangitis), as may the
draining lymph nodes (lymphadenitis).
Chronic Inflammation and Malignancy
The environment created by chronic inflammation promotes
malignant transformation by a number of mechanisms:
1. Increased cell proliferation
2. Oxygen and NO metabolites induced genome damage
3. Chronic immune activation induces an altered cytokine
profile, suppressing cell-mediated immune responses and
creating an environment permissive for malignant growth.
4. Angiogenesis
5. Inhibition of apoptosis
Systemic Effects of Inflammation
1. Fever
2. Acute-phase proteins (C-reactive protein (CRP), fibrinogen, and
serum amyloid A protein (SAA))
3. Leukocytosis or leukopenia
4. increased pulse and blood pressure; decreased sweating,
anorexia, malaise.