innate (non-specific) immunity divisions of the immune system mechanical, chemical, and physical...
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Innate (Non-Specific) Immunity Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents and Opsonizers
• The role of fever
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Body Defenses
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Innate (Non-Specific) Immunity Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents and Opsonizers
• The role of fever
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Nonspecific (Innate) Body DefensesMechanical, Chemical, and Competitive Barriers
Saliva and tears destroy bacteria because they contain lysozyme.
Skin produces acidic sebum to limit bacterial growth.
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Innate (Non-Specific) Immunity Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents and Opsonizers
• The role of fever
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Internal Defenses: Cells and Chemicals Necessary if microorganisms invade deeper tissues
• Phagocytes
• Natural killer (NK) cells
• Inflammatory response (macrophages, mast cells, WBCs, and inflammatory chemicals)
• Antimicrobial proteins (interferons and complement proteins)
• Fever
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Defensive Cells in Non-Specific Defense Phagocytes
(neutrophils and macrophages)
• Engulf foreign material into a vacuole
• Enzymes from lysosomes digest the material
• Free macrophages wander through tissues; fixed macrophages are permanent (e.g liver Kupfer cells, brain microglia
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Figure 21.2b
Lysosome
Phagosome(phagocyticvesicle)
Acidhydrolaseenzymes
(b) Events of phagocytosis.
1 Phagocyteadheres to pathogens or debris.
2 Phagocyte formspseudopods that eventually engulf the particles forming a phagosome.
3 Lysosome fuseswith the phagocytic vesicle, forming a phagolysosome.
4 Lysosomal enzymes digest the particles, leaving a residual body.
5 Exocytosis of thevesicle removes indigestible andresidual material.
Events of Phagocytosis
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Mechanism of Phagocytosis Destruction of pathogens
• Acidification and digestion by lysosomal enzymes
• Respiratory burst
o Release of cell-killing free radicals
o Activation of additional enzymes
• Oxidizing chemicals (e.g. H2O2)
• Defensins (in neutrophils)
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Natural Killer Cells Large granular
lymphocytes
Target cells that lack “self” cell-surface receptors
Induce apoptosis in cancer cells and virus-infected cells
Secrete potent chemicals that enhance the inflammatory response
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Innate (Non-Specific) Immunity Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents and Opsonizers
• The role of fever
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Inflammatory Response Triggered whenever body tissues are injured
or infected
Prevents the spread of damaging agents
Disposes of cell debris and pathogens
Sets the stage for repair
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Inflammatory Response Cardinal signs of acute inflammation:
1. Redness
2. Heat
3. Swelling
4. Pain
(And sometimes 5. Impairment of function)
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Inflammatory Response
Macrophages and epithelial cells of boundary tissues bear Toll-like receptors (TLRs)
TLRs recognize specific classes of infecting microbes
Activated TLRs trigger the release of cytokines that promote inflammation
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Inflammatory Response Inflammatory mediators
• Histamine (from mast cells)
• Blood proteins
• Kinins, prostaglandins (PGs), leukotrienes, and complement
o Released by injured tissue, phagocytes, lymphocytes, basophils, and mast cells
Action of inflammatory chemicals
• Dilation of arterioles, resulting in hyperemia
• Increased permeability of local capillaries and edema (leakage of exudate)
Exudate moves foreign material into lymphatic vessels, delivers clotting proteins to form a scaffold for repair and to isolate the area
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Inflammatory Response - Second Line of Defense
1. Release of histamines, complement, prostaglandins, and kinins from injured cells2. Vasodilation and increased permeability of local capillaries, increasing edema and swelling
3. Activation of pain receptors by swollen tissue pressure4. Attraction of phagocytes and other lymphocytes to the area through chemotaxis: leukocytosis, margination, diapedesis
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Figure 21.4, step 1
Innatedefenses
Internaldefenses
Leukocytosis.Neutrophils enter bloodfrom bone marrow.
Capillary wallBasementmembraneEndothelium
Inflammatorychemicalsdiffusingfrom theinflamed siteact as chemotacticagents.
1
Steps of Attraction of Leukocytes
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Figure 21.4, step 2
Innatedefenses
Internaldefenses
Leukocytosis.Neutrophils enter bloodfrom bone marrow.
Margination.Neutrophils clingto capillary wall.
Capillary wallBasementmembraneEndothelium
Inflammatorychemicalsdiffusingfrom theinflamed siteact as chemotacticagents.
1 2
Steps of Attraction of Leukocytes
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Figure 21.4, step 3
Innatedefenses
Internaldefenses
Leukocytosis.Neutrophils enter bloodfrom bone marrow.
Margination.Neutrophils clingto capillary wall.
Diapedesis.Neutrophils flatten andsqueeze out of capillaries.
Capillary wallBasementmembraneEndothelium
Inflammatorychemicalsdiffusingfrom theinflamed siteact as chemotacticagents.
1 2 3
Steps of Attraction of Leukocytes
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Figure 21.4
Innatedefenses
Internaldefenses
Leukocytosis.Neutrophils enter bloodfrom bone marrow.
Margination.Neutrophils clingto capillary wall.
Diapedesis.Neutrophils flatten andsqueeze out of capillaries.
Chemotaxis.Neutrophilsfollow chemicaltrail.
Capillary wallBasementmembraneEndothelium
Inflammatorychemicalsdiffusingfrom theinflamed siteact as chemotacticagents.
1 2 3
4
Steps of Attraction of Leukocytes
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Innate (Non-Specific) Immunity Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents and Opsonizers
• The role of fever
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Inflammatory Response - Second Line of Defense
1. Release of histamines, complement, prostaglandins, and kinins from injured cells2. Vasodilation and increased permeability of local capillaries, increasing edema and swelling
3. Activation of pain receptors by swollen tissue pressure4. Attraction of phagocytes and other lymphocytes to the area through chemotaxis: leukocytosis, margination, diapedesis
5. Clotting proteins leaking into the area wall off damaged sections; interferon & complement may also be released
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Antimicrobial Proteins: Inteferon
Produced by most leukocytes and lymphocytes
Function
• Reduce inflammation, active macrophages, activate macrophages and mobilize NK cells
• Hinder microorganisms’ ability to reproduce
1. Viral-infected cells secrete IFNs
2. IFNs enter neighboring cells
3. Neighboring cells produce antiviral proteins that block viral reproduction
Genetically engineered IFNs for hepatitis, herpes, MS
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Figure 21.5, step 5
VirusNew viruses
Viral nucleic acid
DNA
mRNA
Nucleus
Interferon
Virusenters cell.
Interferongenes switch on.
Cell producesinterferonmolecules.
Interferonbindingstimulates cell toturn on genes forantiviral proteins.
Antiviralproteins blockviralreproduction.
Host cell 1Infected by virus;makes interferon;is killed by virus
Innate defenses Internal defenses
Host cell 2Binds interferon from cell 1; interferon induces synthesis ofprotective proteins
1
2
34
5
How Interferon Activates the Production of Antivirals
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Antimicrobial Proteins: Complement What they are
• About 20 blood proteins that circulate in an inactive form
• Include C1–C9, factors B, D, and P, and regulatory proteins
Function
• Major mechanism for destroying foreign substances
• Amplifies all aspects of the inflammatory response
• Kills bacteria and certain other cell types by cell lysis
• Enhances both nonspecific and specific defenses
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Complement Activation Two pathways
1. Classical pathway
o Antibodies bind to invading organisms
o C1 binds to the antigen-antibody complexes (complement fixation)
2. Alternative pathway
o Triggered when activated C3, B, D, and P interact on the surface of microorganisms
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Complement Activation Each pathway involves activation of proteins
in an orderly sequence
Each step catalyzes the next
Both pathways converge on C3, which cleaves into C3a and C3b
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Complement Activation Activated complement
• Enhances inflammation
• Promotes phagocytosis
• Causes cell lysis
o C3b initiates formation of a membrane attack complex (MAC)
o MAC causes cell lysis by inducing a massive influx of water
o C3b also causes opsonization, and C3a causes inflammation
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Figure 21.6
Spontaneous activation
Stabilizing factors (B, D, and P)
No inhibitors on pathogensurface
Alternative pathway
Enhances inflammation:
Insertion of MAC and cell lysis(holes in target cell’s membrane)
Complementproteins(C5b–C9)
Pore
Membraneof target cell
+
+
stimulates histamine release,increases blood vessel permeability, attracts phagocytes by chemotaxis, etc.
complex
Opsonization:
+
coats pathogensurfaces, which enhances phagocytosis
Antigen-antibody complexClassical pathway
Transmembrane channel (membrane attack complex) causing lysis
Complement is Activated in Two Ways
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Inflammatory Response - Second Line of Defense
1. Release of histamines, complement, prostaglandins, and kinins from injured cells2. Vasodilation and increased permeability of local capillaries, increasing edema and swelling
3. Activation of pain receptors by swollen tissue pressure4. Attraction of phagocytes and other lymphocytes to the area through chemotaxis: leukocytosis, margination, diapedesis
5. Clotting proteins leaking into the area wall off damaged sections; interferon & complement may also be released
6. Increased local metabolic rate raises the local temperature to increase rate of repair processes7. Production of a fever (stimuated by pyogenic compounds)
. 8. Dead or dying neutrophils, dead cells, and pathogens
may form, walling off a sac of pus to form an abscess.
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Figure 21.3
Tissue injury
Release of chemical mediators(histamine, complement,kinins, prostaglandins, etc.)
Vasodilationof arterioles
Increased capillarypermeability
Local hyperemia(increased blood
flow to area)
Locally increasedtemperature increasesmetabolic rate of cells
Leaked protein-richfluid in tissue spaces
Leaked clottingproteins form interstitialclots that wall off area
to prevent injury tosurrounding tissue
Temporary fibrinpatch forms
scaffolding for repair
Healing
Capillariesleak fluid
(exudate formation)
Attract neutrophils,monocytes, andlymphocytes to
area (chemotaxis)
Release of leukocytosis-inducing factor
Leukocytosis (increased numbers of whiteblood cells in bloodstream)
Leukocytes migrate toinjured area
Margination (leukocytes cling to
capillary walls)
Diapedesis (leukocytes pass through
capillary walls)
Phagocytosis of pathogensand dead tissue cells
(by neutrophils, short-term;by macrophages, long-term)
Area cleared of debris
Pus may form
Signs of inflammation
Initial stimulus
Physiological response
Result
Innate defenses Internal defenses
Possible temporarylimitation ofjoint movement
Heat Redness Pain Swelling
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Fever Abnormally high body temperature
Hypothalmus heat regulation can be reset by pyrogens (secreted by white blood cells)
High temperatures inhibit the release of iron and zinc from liver and spleen needed by bacteria
Fever also increases the speed of tissue repair by increasing metabolic rate
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Innate (Non-Specific) Immunity Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
• Release of Mobilizing Chemicals
• Attraction of Phagocytes
• Antimicrobial Chemicals
o Interferon as an Antiviral
o Complement Proteins as Lytic Agents and Opsonizers
• The role of fever