Innate Defenses:

Inflammation
Chapter 5
 Immunity
• First line of defense
–Innate resistance
• Second line of defense
–Inflammation
• Third line of defense
–Adaptive (acquired)
immunity
 First Line of Defense
• Physical and mechanical
barriers
–Skin
–Linings of the
gastrointestinal,
genitourinary, and
respiratory tracts
 First Line of Defense
• Physical and mechanical
barriers
–Skin
–Linings of the GI,
respiratory, and
genitourinary tracts
• Biochemical barriers
 Second Line of Defense
• Inflammatory response
–How the body deals with
an injury or insult from
physical, chemical, or a
biological agent.
• Infection, mechanical
damage, ischemia,
nutrient deprivation,
 Sprained ankle
• Walking to class in the snow,
you slip and fall on the
sidewalk severely spraining
your ankle.
–What are the symptoms
that you would expect?
signs of inflammation
–Heat (calor)
–Redness (rubor)
–Swelling (tumor)
–Pain (dolar)
–Loss of function (functio
laesa)
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 Inflammation
• Inflammation is a complexly
orchestrated response to an
injury that serves to:
–Limit and control tissue
damage
–Prevent infection by diluting
toxins
–Initiate adaptive immune
 Inflammation
• Acute phase reactions
include:
–Fever
–Shivering
–Tachycardia
–Hypotension
–Loss of appetite
–Vomiting
 Inflammation
• Acute phase reactions
include:
–Fever
–Shivering
–Tachycardia
–Hypotension
–Loss of appetite
–Vomiting
Inflammatory response
–Vascular response
• Vasodilation
• Vascular permeability
• WBC adhesion and
infiltration
Inflammatory response
–Vascular response
• Vasodilation
• Vascular permeability
• WBC adhesion and
infiltration
 Swelling in Tissue
• Transudate
–Fluid driven out of vessels
due to osmotic and
hydrostatic pressures
resulting in swelling in
interstituim
 Swelling in Tissue
• Transudate
–Fluid driven out of vessels
due to osmotic and
hydrostatic pressures
resulting in swelling in
interstitium
• Exudate
–Movement of fluid,
Early inflammation

Vasodilation and
Increased blood flow

Increased vessel
hydrostatic pressure

Increased filtration of
protein poor fluid
(transudate)
Late inflammation

Increased permeability
of vessel wall

Escape of protein rich

fluid (exudate)

Increased tissue osmotic

pressure and decreased vessel
osmotic pressure
Inflammation
 Mast Cells
• Cellular bags of granules
located in the loose
connective tissues close to
blood vessels
–Skin, digestive lining, and
respiratory tract
 Mast Cells
• Activation
–Physical injury, chemical
agents, immunologic
processes, and toll-like
receptors
–Chemical release in two
ways
• Degranulation and
 Mast Cell Degranulation
• Histamine
–Vasoactive amine that
causes temporary, rapid
constriction of the large
blood vessels and the
dilation of the
postcapillary venules
–Retraction of endothelial
Mast Cell Degranulation
 Histamine
• Receptors
–H1 receptor
• Proinflammatory
• Present in smooth
muscle cells of the
bronchi
 Histamine
• Receptors
–H2 receptor
• Anti-inflammatory
• Present on parietal cells
of the stomach mucosa
–Induces the secretion
of gastric acid
Mast Cell Degranulation
• Chemotactic factors
–Neutrophil chemotactic
factor
• Attracts neutrophils
–Eosinophil chemotactic
factor of anaphylaxis
(ECF-A)
 Cell-Derived chemical
mediators
• Vasoactive amines
(histamine/serotonin)
• Arachidonic acid
derivatives
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aspirin

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 corticosteroids
aspirin

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• Leukotrienes
–Product of arachidonic
acid
–Similar effects to
histamine in later stages
• Prostaglandins
–Similar effects to
leukotrienes; they also
induce pain
 Cell-Derived chemical
mediators
• Vasoactive amines
(histamine/serotonin)
• Arachidonic acid
derivatives
• Cytokines and growth
factors
 Cytokines
• Interleukins are produced
primarily by macrophages
and lymphocytes in response
to a pathogen or stimulation
by other products of
inflammation
 Cytokines
• Interferon
– Protects against viral infections
– Produced and released by
virally infected host cells in
response to viral double-
stranded RNA
– Types
• IFN-alpha and IFN-beta
induce production of antiviral
proteins
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 Cytokines

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 Cell-Derived chemical
mediators
• Vasoactive amines
(histamine/serotonin)
• Arachidonic acid
derivatives
• Cytokines and growth
factors
• PAF
 PAF
• Platelet activating factor
activates platelets, AA
metabolism, vasodilation,
vascular permeability,
adhesion and chemotaxis.
• PAF is derived from
basophils, neutrophils,
macrophages, and
endothelial cells
 Cell-Derived chemical
mediators
• Vasoactive amines
(histamine/serotonin)
• Arachidonic acid
derivatives
• Cytokines and growth
factors
• PAF
 NO
• Nitric oxide (NO) is produced
by endothelial cells,
macrophages and neurons
and induces smooth muscle
relaxation and inhibits
platelet aggregation
• With massive macrophage
production what would be
the expected effect on blood
pressure?
– A. no effect
– B.
hypertension(vasoconstriction
)
– C. hypotension(vasodilation)
 Cell-Derived chemical
mediators
• Vasoactive amines
(histamine/serotonin)
• Arachidonic acid
derivatives
• Cytokines and growth
factors
• PAF
 Lysosomal contents
• In addition to enzymes that
will destroy extracellular
components the lysosome
also contains substances to
increase vascular
permeability and
chemotaxis.
 Cell-Derived chemical
mediators
• Vasoactive amines
(histamine/serotonin)
• Arachidonic acid
derivatives
• Cytokines and growth
factors
• PAF
• NO
 Free radicals
• Superoxide and hydrogen
peroxide are produced by
phagocytic cells to poison
viruses and bacteria.
Plasma Protein Systems
• Protein systems
–Kinin system
–Complement system
–Clotting and fibrinolytic
systems
Plasma Protein Systems
• All contain inactive
enzymes (proenzymes)
–Sequentially activated
• First proenzyme is
converted to an active
enzyme
• Substrate of the
activated enzyme
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 Plasma Protein Systems
• Kinin system
–Functions to activate and
assist inflammatory cells
–Primary kinin is bradykinin
–Causes dilation of blood
vessels, pain, smooth
muscle contraction,
vascular permeability, and
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Plasma Protein Systems
• Complement system
–Can destroy pathogens
directly
–Activates or collaborates
with every other
component of the
inflammatory response
–Vascular perm.,
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 Complement system
• Most important
components
– C3a and C5a increase
vascular permeability and
chemotaxis
– C3b and C3bi are opsonins
– C5b-C9 form the membrane
attack complex
 Plasma Protein Systems
• Clotting system
–Forms a fibrinous meshwork
at an injured or inflamed site
–Main substance is an
insoluble protein called fibrin
–Factor XII begins cascade
and amplification
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 Acute Inflammation
• Lasts a few minutes to a
few days with exudate rich
in neutrophils and some
macrophages
• Fever
• Increased WBC circulation
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 Chronic Inflammation
• Inflammation lasting 2
weeks or longer
• Often related to an
unsuccessful acute
inflammatory response
 Chronic Inflammation
• Other causes of chronic
inflammation:
–High lipid and wax content of
a microorganism
–Ability to survive inside the
macrophage
–Toxins
–Chemicals, particulate
matter, or physical irritants
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 Chronic Inflammation
• Characteristics
–Dense infiltration of
lymphocytes and
macrophages
–Granuloma formation
–Epithelioid cell formation
–Giant cell formation
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Chronic Inflammation

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Margination and Adhesion
• Adhesion molecules stick
neutrophils to endothelial
cell surface
• What are the blood flow
changes during acute
inflammation?
• What would happen
without adhesion
Emigration and Chemotaxis
• After adhesion, foot-like
processes push between
endothelial cells
• Cells are subject to
chemotaxis to site of
inflammation
 Phagocytosis
• Neutrophils ingest debris
and bacteria
– Recognition
– Engulfment
– Degradation
 Opsonins
• IgG and C3b coat bacteria
and tag them for rapid
ingestion
– Reguires receptors for both
– Opson:‘to relish’
Phagocytosis
 Exudative Fluids
• Serous exudate
– Watery exudate: indicates early
inflammation
• Fibrinous exudate
– Thick, clotted exudate: indicates
more advanced inflammation
 Exudative Fluids
• Purulent exudate
– Pus: indicates a bacterial infection
• Hemorrhagic exudate
– Exudate contains blood: indicates
bleeding
• Boils are caused by a
bacterial infection of hair
follicles that results in an
acute inflammatory response.
• What are the potential
outcomes of this acute
inflammation?
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• Regeneration/Resolution
• Scarring
• Septicemia
• Persistant inflammation
 Resolution and Repair
• Resolution
– Returning injured tissue to
the original structure and
function
• Repair
– Replacement of destroyed
tissue with scar tissue
– Scar tissue
• Composed primarily of
collagen to restore the
Healing
Healing