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Innate Defenses: Inflammation
Chapter 5
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Host Defenses
Figure 16.1
& NK cells
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Second Line of Defense
� Inflammatory response Ø Caused by a variety of materials
• Infection, mechanical damage, ischemia, nutrient deprivation, temperature extremes, radiation, etc.
Ø Local manifestations
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Second Line of Defense
� Inflammatory response Ø Vascular response
• Blood vessel dilation, increased vascular permeability and leakage, white blood cell adherence to the inner walls of the vessels and migration through the vessels
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Inflammation
� Goals Ø Limit and control the inflammatory process Ø Prevent and limit infection and further damage Ø Initiate adaptive immune response Ø Initiate healing Ø DOUBLE-edged sword
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� Vascular Stage Ø Injured tissue releases inflammatory mediators
• Prostaglandins, Leukotriene, etc. Ø Arterioles and Venules dilate
• Increasing blood flow to injured area � Redness and warmth result
Ø Capillary endothelial cells separate and become more permeable
• Allowing exudate to escape into the tissues � Swelling and pain result
Acute Inflammation
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� Leukocytes express adhesive proteins
� Attach to the blood vessel lining
� Squeeze between the cells
� Follow the inflammatory mediators to the injured area
Leukocytes Enter Damaged Area
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� Leukocytes Release Many Inflammatory Mediators at the Injured Area Ø Histamine and serotonin
Ø Platelet-activating factor
Ø Cytokines
Ø Nitric oxide
Inflammatory Mediators
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� Acute Phase Response Ø Leukocytes release inflammatory mediators
(interleukins and tumor necrosis factor) • Affect thermoregulatory center à fever • Affect central nervous system à lethargy • Skeletal muscle breakdown à myalgia
Ø Liver increases production of fibrinogen and C-reactive protein
• Facilitate clotting • Bind to pathogens • Moderate inflammatory responses
Systemic Response to Inflammation
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Inflammation
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Mast Cells
� Cellular bags of granules located in the loose connective tissues close to blood vessels Ø Skin, digestive lining, and respiratory tract
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Mast Cell Degranulation
� Histamine Ø Vasoactive amine that causes temporary, rapid
constriction of the large blood vessels and the dilation of the postcapillary venules
Ø Retraction of endothelial cells lining the capillaries
Ø Receptors • H1 receptor (proinflammatory) • H2 receptor (anti-inflammatory)
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Mast Cell Degranulation
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Histamine
� Receptors Ø H1 receptor
• Proinflammatory • Present in smooth muscle cells of the bronchi
Ø H2 receptor • Anti-inflammatory • Present on parietal cells of the stomach mucosa
� Induces the secretion of gastric acid
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Plasma Protein Systems
� Protein systems Ø Complement system Ø Coagulation system Ø Kinin system
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Plasma Protein Systems
� Complement system Ø Can destroy pathogens directly Ø Activates or collaborates with every other
component of the inflammatory response Ø Pathways
• Classical • Lectin • Alternative
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The Complement System
Figure 16.10
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Plasma Protein Systems
� Coagulation (clotting) system Ø Forms a fibrinous meshwork at an injured or
inflamed site • Prevents the spread of infection • Keeps microorganisms and foreign bodies at the site
of greatest inflammatory cell activity • Forms a clot that stops bleeding • Provides a framework for repair and healing
Ø Main substance is an insoluble protein called fibrin
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Plasma Protein Systems
� Kinin system Ø Functions to activate and assist inflammatory
cells Ø Primary kinin is bradykinin Ø Causes dilation of blood vessels, pain, smooth
muscle contraction, vascular permeability, and leukocyte chemotaxis
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Phagocytosis
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Phagocytes
� Neutrophils Ø Also referred to as polymorphonuclear
neutrophils (PMNs) Ø Predominate in early inflammatory responses Ø Ingest bacteria, dead cells, and cellular debris Ø Cells are short lived and become a component
of the purulent exudate Ø The WBC most elevated during bacterial
infection
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Phagocytes
� Monocytes and macrophages Ø Monocytes are produced in the bone marrow,
enter the circulation, and migrate to the inflammatory site, where they develop into macrophages
Ø Macrophages typically arrive at the inflammatory site 24 hours or later after neutrophils
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Phagocytes
� Eosinophils Ø Mildly phagocytic Ø Duties
• Defense against parasites and regulation of vascular mediators
The WBC most elevated during parasite infection and some allergic reactions
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� Natural killer (NK) cells Ø Function is to recognize and eliminate cells
infected with viruses and some function in eliminating cancer cells
� Platelets Ø Activation results in degranulation and
interaction with components of the coagulation system
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Cytokines
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Cytokines
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Exudative Fluids
� Serous exudate Ø Watery exudate: indicates early inflammation
� Fibrinous exudate Ø Thick, clotted exudate: indicates more
advanced inflammation
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Exudative Fluids
� Purulent exudate Ø Pus: indicates a bacterial infection
� Hemorrhagic exudate Ø Exudate contains blood: indicates bleeding
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Systemic Manifestations of Inflammation
� Fever Ø Caused by exogenous (microbes) and
endogenous (cytokines, chemical mediators) pyrogens
Ø Act directly on the hypothalamus
� Leukocytosis Ø Increased numbers of circulating leukocytes
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Fever
• Inflammatory Mediators Enter the Brain
• Raise the “Set Point” for Thermostat in Hypothalmaus
• The Body Thinks its Too Cold
• Heat Production “Fever” & “Chills”
• Shivering & Vasoconstriction
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Fever
• Temperature Rises to New “Set Point”
• Body Thinks its Warm Enough • “Fever”
• Begins to Lower Temperature
• Sweating • Vasodilation “Flushing”
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Chronic Inflammation
� Inflammation lasting 2 weeks or longer � Often related to an unsuccessful acute
inflammatory response
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Chronic Inflammation
� Other causes of chronic inflammation: Ø High lipid and wax content of a microorganism
(TB) Ø Ability to survive inside the macrophage Ø Toxins Ø Chemicals, particulate matter, or physical
irritants
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Chronic Inflammation
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� Macrophages accumulate in the damaged area and keep releasing inflammatory mediators
� Nonspecific chronic inflammation
Ø Fibroblasts proliferate
Ø Scar tissue forms
� Granulomatous lesions
Ø Macrophages mass together around foreign bodies
Ø Connective tissue surrounds and isolates the mass
Chronic Inflammation
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Resolution and Repair
� Regeneration � Resolution
Ø Returning injured tissue to the original structure and function
� Repair Ø Replacement of destroyed tissue with scar
tissue Ø Scar tissue
• Composed primarily of collagen to restore the tensile strength of the tissue
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Tissue Regeneration
• Stable cells - normally stop dividing when growth ceases � Capable of undergoing regeneration when confronted with an
appropriate stimulus • Permanent cells - cannot undergo mitotic division
� Nerve cells, skeletal muscle cells, and cardiac muscle cells � Once destroyed, they are replaced with fibrous scar tissue that
lacks the functional characteristics of the destroyed tissue.
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Resolution and Repair
� Debridement Ø Cleaning up the dissolved clots,
microorganisms, erythrocytes, and dead tissue cells
� Healing Ø Filling in the wound Ø Sealing the wound (epithelialization) Ø Shrinking the wound (contraction)
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Healing
� Primary intention Ø Wounds that heal under conditions of minimal
tissue loss � Secondary intention
Ø Wounds that require a great deal more tissue replacement
• Open wound
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Healing
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Healing
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Dysfunctional Wound Healing
� Dysfunction during inflammatory response Ø Hemorrhage Ø Fibrous adhesion Ø Infection Ø Excess scar formation
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Dysfunctional Wound Healing
� Dysfunction during inflammatory response Ø Wound sepsis especially burns Ø Diabetes: have small vessel breakdown
apoptosis due to past and present elevated blood sugar, decreased immune response so infected wounds, Hb does not liberate O2 in high sugar environment
Ø Poor nutrition decreases collagen formation and integrity
Ø Anti-inflammatory steroids
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Dysfunctional Wound Healing
� Dysfunction during reconstructive phase Ø Impaired collagen matrix assembly
• Keloid scar: raised scar that extends beyond original wound boundaries, higher incidence in AA
• Hypertrophic scar: raised scar but within original wound boundaries
Ø Impaired epithelialization • Anti-inflammatory steroids, hypoxemia, and
nutritional deficiencies
Ø Impaired contraction • Contracture is needed for wound closure but if
excessive like in burns it inhibits mobility
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Dysfunctional Wound Healing
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Dysfunctional Wound Healing
� Wound disruption Ø Dehiscence
• Wound pulls apart at the suture line � Excessive strain and obesity are causes
• Increases risk of wound sepsis
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Older Adults
� Impaired inflammation is likely a result of chronic illness Ø Diabetes, cardiovascular disease, etc.
� Chronic medication intake decreases the inflammatory response
� Healing response is diminished because of skin’s loss of regenerative ability
� Infections are more common in older adults