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

• 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

Inflammation

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

• Transudate –Fluid driven out of vessels due to osmotic and hydrostatic pressures resulting in swelling in interstitium • Exudate –Movement of fluid,

Swelling in Tissue

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

• Activation –Physical injury, chemical agents, immunologic processes, and toll-like receptors –Chemical release in two ways • Degranulation and

Mast Cells

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

• Receptors –H1 receptor

Histamine

• Proinflammatory • Present in smooth muscle cells of the bronchi

• Receptors –H2 receptor

Histamine

• 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

• 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 doublestranded RNA – Types • IFN-alpha and IFN-beta induce production of antiviral proteins
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Cytokines

Cytokines

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Cell-Derived chemical mediators
• Vasoactive amines (histamine/serotonin) • Arachidonic acid derivatives • Cytokines and growth factors • PAF

• Platelet activating factor activates platelets, AA metabolism, vasodilation, vascular permeability, adhesion and chemotaxis. • PAF is derived from basophils, neutrophils, macrophages, and endothelial cells

PAF

Cell-Derived chemical mediators
• Vasoactive amines (histamine/serotonin) • Arachidonic acid derivatives • Cytokines and growth factors • PAF

• Nitric oxide (NO) is produced by endothelial cells, macrophages and neurons and induces smooth muscle relaxation and inhibits platelet aggregation

NO

• 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

• In addition to enzymes that will destroy extracellular components the lysosome also contains substances to increase vascular permeability and chemotaxis.

Lysosomal contents

Cell-Derived chemical mediators • Vasoactive amines
• • • • (histamine/serotonin) Arachidonic acid derivatives Cytokines and growth factors PAF NO

• Superoxide and hydrogen peroxide are produced by phagocytic cells to poison viruses and bacteria.

Free radicals

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