innate defenses: inflammation · 2014. 9. 8. · elsevier items and derived items © 2008 by mosby,...

Elsevier items and derived items © 2008 by Mosby, Inc., an affiliate of Elsevier Inc. Some material was previously published.

Innate Defenses: Inflammation

Chapter 5


Host Defenses

Figure 16.1

& NK cells


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


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


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


�  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


�  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


�  Leukocytes Release Many Inflammatory Mediators at the Injured Area Ø Histamine and serotonin

Ø Platelet-activating factor

Ø Cytokines

Ø Nitric oxide

Inflammatory Mediators


�  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


Inflammation


Mast Cells

�  Cellular bags of granules located in the loose connective tissues close to blood vessels Ø Skin, digestive lining, and respiratory tract


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)


Mast Cell Degranulation


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


Plasma Protein Systems

�  Protein systems Ø Complement system Ø Coagulation system Ø Kinin system



�  Complement system Ø Can destroy pathogens directly Ø Activates or collaborates with every other

component of the inflammatory response Ø Pathways

•  Classical •  Lectin •  Alternative


The Complement System

Figure 16.10



�  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



�  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


Phagocytosis


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


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


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


�  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


Cytokines


Exudative Fluids

�  Serous exudate Ø Watery exudate: indicates early inflammation

�  Fibrinous exudate Ø  Thick, clotted exudate: indicates more

advanced inflammation


Exudative Fluids

�  Purulent exudate Ø Pus: indicates a bacterial infection

�  Hemorrhagic exudate Ø Exudate contains blood: indicates bleeding


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


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


Fever

•  Temperature Rises to New “Set Point”

•  Body Thinks its Warm Enough •  “Fever”

•  Begins to Lower Temperature

•  Sweating •  Vasodilation “Flushing”


Chronic Inflammation

�  Inflammation lasting 2 weeks or longer �  Often related to an unsuccessful acute

inflammatory response



�  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


�  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



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


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.


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)


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


Healing


Dysfunctional Wound Healing

�  Dysfunction during inflammatory response Ø Hemorrhage Ø  Fibrous adhesion Ø  Infection Ø Excess scar formation



�  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



�  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



�  Wound disruption Ø Dehiscence

•  Wound pulls apart at the suture line �  Excessive strain and obesity are causes

•  Increases risk of wound sepsis


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

innate defenses: inflammation · 2014. 9. 8. · elsevier items and derived items © 2008 by mosby,...

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