Inflammation ADW MKDU PPDS 1 FK UNAIR 2023

Inflammmation
Agung Dwi Wahyu Widodo

MD, MSc, MClinMed, PhD, Clin Microbiologist
Department of Clinical Microbiology
Faculty of Medicine, Universitas Airlangga Surabaya
Subject
• Inflammation
• Acute Inflammation
• Chronic Inflammation
• Effect Systemic of Inflammation
• Conclusion
Map of Inflammation
Inflammation Definition
(Kumar, Abbas and Aster, 2018)
• Inflammation is a response of vascularized

tissues to infections and tissue damage that
brings cells and molecules of host defense
from the circulation to the sites where they
are needed, to eliminate the offending
agents.
The steps of
1 the
inflammatory
response
2 (1) Recognition
Pathogen
(2) recruitment of
3 leukocytes
(3) removal of the
4 agent,
(4) regulation (control)
of the response
(5) resolution (repair).
5
Features of
Acute and Chronic Inflammation
Disorders Caused by Inflammatory Reactions
The components of acute and chronic
inflammatory responses
Normal Alveoli of Lung
Bacterial Pneumoniae
Cardinal Sign Of Inflammation
• The external manifestations of inflammation, often
called its cardinal signs, are heat (calor), redness
(rubor), swelling (tumor), pain (dolor), and loss of
function (functio laesa).
• The first four of these were described more than
2000 years ago by a Roman encyclopedist named
Celsus
• The fifth was added in the late 19th century by
Rudolf Virchow
• These manifestations occur as consequences of the
vascular changes and leukocyte recruitment and
activation
Vascular and cellular reactions of acute
inflammation
Stimuli for Acute Inflammation
• Stimuli for Acute Inflammation:
• Infections (bacterial, viral, fungal, parasitic)
• Trauma (blunt and penetrating) and various physical
and chemical agents (e.g., thermal injury, such as burns or
frostbite; irradiation; toxicity from certain environ-
mental chemicals)
• Tissue necrosis (from any cause), including ischemia (as
in a myocardial infarct) and physical and chemical injury
• Foreign bodies (splinters, dirt, sutures, crystal deposits)
• Immune reactions (also called hypersensitivity reactions
) against environmental substances or against “self”
tissues.
Formation of transudates and exudates
Endothelial and Leukocyte Adhesion Molecules
Nature of leukocyte infiltrates in
inflammatory reactions
Leukocyte Effector Mechanisms
• Leukocytes can eliminate microbes and dead cells

by phagocytosis, followed by their destruction in
phagolysosomes.
• Destruction is caused by free radicals (ROS, NO)
generated in activated leukocytes and lysosomal
enzymes.
• Enzymes and ROS may be released into the
extracellular environment.
• The mechanisms that function to eliminate microbes
and dead cells (the physiologic role of inflammation)
are also capable of damaging normal tissues (the
pathologic consequences of inflammation).
Phagocytosis
Sequence of Events in Acute Inflammation
• The vascular changes in acute inflammation are character-ized by
increased blood flow secondary to arteriolar and capillary bed dilation
(erythema and warmth).
• Increased vascular permeability, as a consequence of either widening
of interendothelial cell junctions of the venules or direct endothelial
cell injury, results in an exudate of protein-rich extravascular fluid (tissue
edema).
• The leukocytes, initially predominantly neutrophils, adhere to the
endothelium via adhesion molecules and then leave the microvasculature
and migrate to the site of injury under the influence of chemotactic
agents.
• Phagocytosis, killing, and degradation of the offending agent follow.
• Genetic or acquired defects in leukocyte functions give rise to
recurrent infections.
• The outcome of acute inflammation may be removal of the exudate
with restoration of normal tissue architecture (resolution); transition
to chronic inflammation; or extensive destruction of the tissue resulting
in scarring.
Actions of the Principal Mediators of
Inflammation
Production of arachidonic acid metabolites
and their roles in inflammation
Plasma Protein–Derived Mediators of
Inflammation
• Plasma Protein–Derived Mediators of Inflammation:
• Complement proteins: Activation of the
complement system by microbes or antibodies leads to
the generation of multiple breakdown products,
which are responsible for leukocyte chemotaxis,
opsonization and phagocytosis of microbes and other
particles, and cell killing.
• Coagulation proteins: Activated factor XII triggers
the clotting, kinin, and complement cascades and
activates the fibrinolytic system.
• Kinins: Produced by proteolytic cleavage of
precursors, this group mediates vascular reaction and
pain
The activation and functions of the
complement system
Outcomes of acute inflammation
Features of Chronic Inflammation
• Prolonged host response to persistent stimulus
• Caused by microbes that resist elimination, immune
responses against self and environmental antigens, and
some toxic substances (e.g., silica); underlies many
important diseases
• Characterized by persistent inflammation, tissue injury,
attempted repair by scarring, and immune response
• Cellular infiltrate consisting of activated macrophages,
lymphocytes, and plasma cells, often with prominent
fibrosis
• Mediated by cytokines produced by macrophages and
lymphocytes (notably T lymphocytes), with a tendency to
an amplified and prolonged inflammatory response owing
to bidirectional interactions between these cells
Macrophage–lymphocyte interactions
in chronic inflammation
Systemic Effects of Inflammation
• Fever: cytokines (TNF, IL-1) stimulate production of
prostaglandins in hypothalamus
• Production of acute-phase proteins: C-reactive
protein, others; synthesis stimulated by cytokines
(IL-6, others) acting on liver cells
• Leukocytosis: cytokines (CSFs) stimulate production
of leukocytes from precursors in the bone marrow
• In some severe infections, septic shock: fall in blood
pres -sure, disseminated intravascular coagulation,
metabolic abnormalities; induced by high levels of TNF
The induction of fever during infection
Innate
Responses in
Fever
Adaptive Responses in Fever
Regulation of Inflammations
Conclusion

Inflammation ADW MKDU PPDS 1 FK UNAIR 2023

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Inflammmation

Agung Dwi Wahyu Widodo

• Inﬂammation is a response of vascularized

• Leukocytes can eliminate microbes and dead cells

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