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© 2015 Pearson Education, Inc.
Chapter 15
© 2015 Pearson Education, Inc.
An Overview of the Body's Defenses
• Resistance to most plant and animal pathogens
• Species resistance
• Due to physiological processes of humans that are
incompatible with those of the pathogen
• Correct chemical receptors are not present on human
cells
• Conditions may be incompatible with those needed for
pathogen's survival
• Humans do not have innate resistance to a
number of pathogens
© 2015 Pearson Education, Inc.
An Overview of the Body's Defenses
• Three main lines of defense
• Innate immunity — first two lines of defense
• External physical barriers to pathogens
• Protective cells, bloodborne chemicals, and processes
• Adaptive immunity
© 2015 Pearson Education, Inc.
Host Defenses: Overview
© 2015 Pearson Education, Inc.
An Overview of the Body's Defenses
• Tell Me Why
• Why aren't the body's skin and mucous membrane
barriers significant factors in your resistance to infection
by hyperthermophiles?
© 2015 Pearson Education, Inc.
The Body's First Line of Defense
• Structures, chemicals, and processes that work to
prevent pathogens entering the body
• Skin and mucous membranes of the respiratory,
digestive, urinary, and reproductive systems
© 2015 Pearson Education, Inc.
The Body's First Line of Defense
• The Role of Skin in Innate Immunity
• Skin is composed of two major layers
• Epidermis
• Multiple layers of tightly packed cells
• Few pathogens can penetrate these layers
• Shedding of dead skin cells removes
microorganisms
• Epidermal dendritic cells phagocytize pathogens
• Dermis
• Collagen fibers help skin resist abrasions that could
introduce microorganisms
© 2015 Pearson Education, Inc.
Figure 15.1 A scanning electron micrograph of the surface of human skin.
© 2015 Pearson Education, Inc.
The Body's First Line of Defense
• The Role of Skin in Innate Immunity
• Skin has chemicals that defend against pathogens
• Antimicrobial peptides (defensins) secreted by dermal
cells
• Perspiration secreted by sweat glands
• Salt inhibits growth of pathogens
• Antimicrobial peptides called dermcidins act against
many bacteria and fungi
• Lysozyme destroys cell wall of bacteria
© 2015 Pearson Education, Inc.
The Body's First Line of Defense
• The Role of Skin in Innate Immunity
• Skin has chemicals that defend against pathogens
• Sebum secreted by sebaceous (oil) glands
• Helps keep skin pliable and less likely to break or tear
• Lowers skin pH to a level inhibitory to many bacteria
© 2015 Pearson Education, Inc.
The Body's First Line of Defense
• The Role of Mucous Membranes in Innate Immunity
• Mucous membranes line all body cavities open to environment
• Two distinct layers
• Epithelium
• Thin, outer covering of the mucous membranes
• Epithelial cells are living
• Tightly packed to prevent entry of many pathogens
• Continual shedding of cells carries away microorganisms
• Dendritic cells below epithelium phagocytize pathogens
• Goblet and ciliated columnar cells help remove invaders
• Deeper connective layer that supports the epithelium
• Produce chemicals that defend against pathogens
© 2015 Pearson Education, Inc.
Nasal cavity
Pharynx
Tongue
Epiglottis
Larynx
(voice box)
Esophagus
Trachea
Bronchus
Bronchioles
Figure 15.2 The structure of the respiratory system, which is lined with a mucous membrane.
© 2015 Pearson Education, Inc.
© 2015 Pearson Education, Inc.
The Body's First Line of Defense
• The Role of the Lacrimal Apparatus in Innate
Immunity
• Lacrimal apparatus
• Produces and drains tears
• Blinking spreads tears and washes surface of the eye
• Lysozyme in tears destroys bacteria
© 2015 Pearson Education, Inc.
Nasolacrimal duct
Lacrimal
apparatus
Lacrimal
glands
Lacrimal
gland duct
Lacrimal
canal
Nasolacrimal
duct
Paranasal
sinus
Pharynx
Trachea Esophagus
Lateral viewAnterior view
Figure 15.3 The lacrimal apparatus.
© 2015 Pearson Education, Inc.
The Body's First Line of Defense
• The Role of Normal Microbiota in Innate
Immunity
• Microbial antagonism
• Normal microbiota compete with potential pathogens
• Activities of normal microbiota make it hard for
pathogens to compete
• Consume nutrients
• Create an environment unfavorable to other
microorganisms
• Help stimulate the body's second line of defense
• Promote overall health by providing vitamins to host
© 2015 Pearson Education, Inc.
The Body's First Line of Defense
• Other First-Line Defenses
• Antimicrobial peptides
• Present in skin, mucous membranes, neutrophils
• Act against a variety of microbes
• Work in several ways
• Other processes and chemicals
• Many organs secrete chemicals with antimicrobial
properties
© 2015 Pearson Education, Inc.
© 2015 Pearson Education, Inc.
© 2015 Pearson Education, Inc.
The Body's First Line of Defense
• Tell Me Why
• Some strains of Staphylococcus aureus produce
exfoliative toxin, a chemical that causes portions of the
entire outer layer of the skin to be sloughed off in a
disease called scalded skin syndrome. Given that cells
of the outer layer are going to fall off anyway, why is this
disease dangerous?
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Operates when pathogens penetrate the skin or
mucous membranes
• Composed of cells, antimicrobial chemicals, and
processes
• Many of these components are contained or originate in
the blood
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Defense Components of Blood
• Plasma
• Mostly water containing electrolytes, dissolved gases,
nutrients, and proteins
• Serum is the fluid remaining when clotting factors are
removed
• Contains iron-binding compounds
• Iron is needed for metabolism
• Some microbes produce iron-binding proteins
(siderophores)
• Complement proteins and antibodies are also found in
plasma
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Defense Components of Blood
• Defensive blood cells: leukocytes
• Cells and cell fragments in plasma are called formed elements
• Three types of formed elements
• Erythrocytes
• Carry oxygen and carbon dioxide in the blood
• Platelets
• Involved in blood clotting
• Leukocytes
• Involved in defending the body against invaders
• Classified as granulocytes and agranulocytes
© 2015 Pearson Education, Inc.
Leukocytes
Adaptive immunityGas
transportation
Innate immunity, second line of defense
PhagocytosisInflammationClotting,
inflammation
Myeloid
stem cell
Lymphoid
stem cell
Erythroid
stem cell
Blood stem cell in bone marrow
Erythrocyte Platelets Basophil Neutrophil Eosinophil Monocyte Lymphocyte
Figure 15.4 A schematic representation of hematopoiesis.
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Defense Components of Blood
• Defensive blood cells: leukocytes
• Granulocytes
• Contain large granules that stain different colors
• Three types
• Basophils – stain blue with basic dye methylene blue
• Eosinophils – stain red/orange with acidic dye eosin
• Neutrophils – stain lilac with mix of acidic and basic dyes
• Neutrophils and eosinophils
• Phagocytize pathogens
• Capable of diapedesis
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Defense Components of Blood
• Defensive blood cells: leukocytes
• Agranulocytes
• Cytoplasm appears uniform under a light microscope
• Two types
• Lymphocytes
• Most involved in adaptive immunity
• Natural killer lymphocytes
• Monocytes
• Leave the blood and mature into macrophages
• Phagocytic cells that devour foreign objects
© 2015 Pearson Education, Inc.
Basophil 0.5–1%
Eosinophil 2–4%
Neutrophil 60–70%
Lymphocyte 20–25%
Monocyte 3–8%
Granulocytes
Agranulocytes
Figure 15.5 Leukocytes as seen in stained blood smears.
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Defense Components of Blood
• Defensive blood cells: leukocytes
• Lab analysis of leukocytes
• Differential white blood cell count can signal disease
• Increased eosinophils indicate allergies or
parasitic worm infection
• Bacterial diseases often show increase in
leukocytes and neutrophils
• Viral infections show increase in lymphocytes
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Phagocytosis
• Cells capable of phagocytosis are called phagocytes
• Phagocytosis is not completely understood
• Can be divided into six stages
• Chemotaxis
• Adherence
• Ingestion
• Maturation
• Killing
• Elimination
© 2015 Pearson Education, Inc.
Phagocytosis: Overview
© 2015 Pearson Education, Inc.
Chemotaxis of
phagocyte
to microbes Neisseria
(microbes)
Pseudopodia move
(chemotaxis)
Adherence
Ingestion of microbes
by phagocytes
Fusion of a
series of vesicles,
including lysosomes
Phagosome
Killing of
microbes by
enzymes and
other chemicals
Elimination
by exocytosis
Residual
body
Phagolysosome
Nucleus
Lysosome
Golgi body
Phagocyte
Pseudopod
2
1
3
4
5
6
Figure 15.6 The events in phagocytosis.
© 2015 Pearson Education, Inc.
Phagocytosis: Mechanism
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Nonphagocytic Killing
• Killing by eosinophils
• Attack parasitic helminths by attaching to their surface
• Secrete toxins that weaken or kill the helminth
• Eosinophilia is often indicative of a helminth
infestation or allergies
• Eosinophil mitochondrial DNA and proteins form structure
that kills some bacteria
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Nonphagocytic Killing
• Killing by natural killer lymphocytes
• Secrete toxins onto surface of virally infected cells and
tumors
• Differentiate normal body cells because they have
membrane proteins similar to the NK cells
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Nonphagocytic Killing
• Killing by neutrophils
• Can destroy microbes without phagocytosis
• Produce chemicals that kill nearby invaders
• Generate extracellular fibers called neutrophil
extracellular traps (NETs) that bind to and kill bacteria
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Nonspecific Chemical Defenses Against
Pathogens
• Toll-like receptors (TLRs)
• Integral membrane proteins produced by phagocytic cells
• Bind pathogen-associated molecular patterns (PAMPs)
• Initiate defensive responses
• Apoptosis
• Secretion of inflammatory mediators
• Stimulate adaptive immune response
© 2015 Pearson Education, Inc.
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Nonspecific Chemical Defenses Against
Pathogens
• NOD proteins
• Cytosolic proteins that bind PAMPs
• Trigger inflammation, apoptosis, and other innate
responses
• Mechanism of action still being researched
• Mutations in NOD genes associated with some
inflammatory bowel diseases
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Nonspecific Chemical Defenses Against
Pathogens
• Interferons
• Protein molecules released by host cells to nonspecifically
inhibit the spread of viral infections
• Cause many symptoms associated with viral infections
• Two types
• Types I (alpha and beta)
• Type II (gamma)
© 2015 Pearson Education, Inc.
Binding triggers
transcription
and translation of
inactive antiviral
proteins (AVPs).
Same
neighboring
cell now protected
at the later time
Active AVPs degrade
mRNA and bind to
ribosomes, which stops
protein synthesis and
viral replication.
When the second
cell becomes infected
with viruses, double-
stranded RNA
of the virus
activates AVP.
Meanwhile, the
infected cell dies,
releasing viruses.
Interferon is released,
diffuses to neighboring
uninfected cells, and
binds to receptors.
Viral replication
in cell triggers
transcription and
translation of
IFN-α or IFN-β,
depending on
type of host cell.
mRNA
Inactive
AVPs
Uninfected
neighboring cell
Infected cell
Interferon receptor
IFN
gene
Double-
stranded
RNA
Virus
Virus infects cell.
Nucleus
mRNA
IFN
Infected cell
at a later time
Time
passes
mRNA
Inactive AVP
Double-
stranded
viral RNA
Active AVPs
Time
passes
Ribosome
AVP
gene
1
2
5
3
4
7
6
Figure 15.7 The actions of alpha and beta interferons.
© 2015 Pearson Education, Inc.
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Nonspecific Chemical Defenses Against
Pathogens
• Complement
• Set of serum proteins designated numerically according to
their order of discovery
• Complement activation results in lysis of the foreign cell
• Indirectly trigger inflammation and fever
• Complement can be activated in three ways
• Classical pathway
• Alternative pathway
• Lectin pathway
© 2015 Pearson Education, Inc.
Complement: Overview
© 2015 Pearson Education, Inc.
Membrane attack
complex and cell lysis
Inflammation
C5 convertase
C5 C5a + C5b
Opsonization
Inflammation
Activation
(C3 C3a + C3b)
Complement cascade
Complement
proteins
1, 2, 4
Factors B,
D, and P
C3b
Antibody
Lectins
Endotoxin and
glycoproteins
C3bAntigen Mannose
Lectin pathwayAlternative pathwayClassical pathway
Figure 15.8 Pathways by which complement is activated.
© 2015 Pearson Education, Inc.
Membrane
attack
complex
Cytoplasmic
membrane
C5b combines with C6, C7, C8,
and several molecules of C9
to form a membrane attack
complex (MAC). A MAC drills a
circular hole in the pathogen’s
cytoplasmic membrane,
leading to lysis of the cell.
Causes chemotaxis
of phagocytes
and triggers
inflammation
Pathogen
Antigen
Antibody
C1 becomes
an active enzyme
when it binds to
antibody-antigen
complexes.
Enzyme C1
splits molecules
of C2 and of C4.
C3b combines
with the remaining
fragments of C2
and C4 to form a
third enzyme.
Fragments of C2
and C4 combine
to form a second
enzyme that
splits C3 into
C3a and C3b.
Causes chemotaxis of
phagocytes and triggers
inflammation
This enzyme cleaves
C5 into C5a and C5b.
Causes
inflammation
Acts as
opsonin
Enzymatic C1
H2O
H2O
H2O
C9
C9C9
C9
C9
C9
C9
C9 C9
C9
C8 C7
C6C5b
H2O
C5b
C5a1
2
3
4
5
6
Figure 15.9 The classical pathway and complement cascade.
© 2015 Pearson Education, Inc.
Membrane attack complex
Figure 15.10 Membrane attack complexes.
© 2015 Pearson Education, Inc.
Complement: Activation
© 2015 Pearson Education, Inc.
Complement: Results
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Nonspecific Chemical Defenses Against
Pathogens
• Complement
• Inactivation of complement
• Body's own cells withstand complement cascade
• Proteins on many cells bind and break down
activated complement proteins
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Inflammation
• Nonspecific response to tissue damage from various
causes
• Characterized by redness, heat, swelling, and pain
• Two types
• Acute
• Chronic
© 2015 Pearson Education, Inc.
Inflammation: Overview
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Inflammation
• Acute inflammation
• Develops quickly and is short lived
• Is typically beneficial
• Is important in the second line of defense
• Dilation and increased permeability of the blood vessels
• Migration of phagocytes
• Tissue repair
• Chronic inflammation
• Long-lasting
• Damage to tissues can cause disease
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Inflammation
• Dilation and increased permeability of blood vessels
• Initial response to injury or invasion of pathogens
• Release of inflammatory mediators triggers dilation of
blood vessels
• Bradykinin
• Prostaglandins
• Leukotrienes
• Histamine
• Signs and symptoms of inflammation can be blocked with
antihistamines or antiprostaglandins
© 2015 Pearson Education, Inc.
Granule
containing
chemicals
Inflammatory mediators
C3a
C5a
C5a
C3a
Figure 15.11 The stimulation of inflammation by complement.
© 2015 Pearson Education, Inc.
Mediator
Blood
flow
Dilated
capillaries
After
Venule
Capillaries
BeforeArteriole
Blood
flow
Figure 15.12 The dilating effect of inflammatory mediators on small blood vessels.
© 2015 Pearson Education, Inc.
Monocyte squeezing
through interstitial space
(diapedesis)
More fluidSmall amount
of fluid
Monocyte
More fluid
and antimicrobial
chemicals
Interstitial
spaces
Small amount
of fluidVenule wall
Normal permeability
of venule
Increased permeability of venule
during inflammation
Figure 15.13 Increased vascular permeability during inflammation.
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Inflammation
• Migration of phagocytes
• Increased blood flow delivers leukocytes to site of
infection
• Attach to receptors lining vessels via margination
• Squeeze between vessel's walls
• Attracted to site of infection by chemotactic factors
• Neutrophils arrive first, followed by monocytes
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Inflammation
• Tissue repair
• Final stage of inflammation
• Delivers extra nutrients and oxygen to site
• Some sites cannot be fully repaired and form scar tissue
© 2015 Pearson Education, Inc.
Bacteria
A cut penetrates the epidermis
barrier, and bacteria invade.
Damaged cells release
prostaglandins, leukotrienes,
and histamine (shown in
green here).
Increased permeability allows
antimicrobial chemicals and
clotting proteins to seep into
damaged tissue but also
results in swelling, pressure on
nerve endings, and pain.
Nerve ending
HeatSwelling
Prostaglandins and
leukotrienes make vessels
more permeable. Histamine
causes vasodilation, increasing
blood flow to the site.
Macrophages and neutrophils
squeeze through walls of
blood vessels (diapedesis).
Blood clot forms.
More phagocytes migrate to
the site and devour bacteria.
Accumulation of damaged
tissue and leukocytes forms
pus.
Undifferentiated stem cells
repair the damaged tissue.
Blood clot is absorbed or falls
off as a scab.
1
2
5
3
4
6
7
8
9
Figure 15.14 An overview of the events in inflammation following a cut and infection.
© 2015 Pearson Education, Inc.
© 2015 Pearson Education, Inc.
Inflammation: Steps
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Fever
• Body temperature over 37°C
• Results when pyrogens trigger the hypothalamus to
increase the body's core temperature
• Various types of pyrogens
• Bacterial toxins
• Cytoplasmic contents of bacteria released by lysis
• Antibody-antigen complexes
• Pyrogens released by phagocytes that have phagocytized
bacteria
• Exact mechanism of fever is not known
© 2015 Pearson Education, Inc.
Hypothalamus
secretes
prostaglandin,
which resets
hypothalamic
thermostat.
Nerve impulses
cause shivering,
higher metabolic rate,
inhibition of sweating,
and vasoconstriction.
These processes increase body
temperature to the point set by
the hypothalamic thermostat.
Chemicals secreted
by phagocytes
travel in blood to
hypothalamus.
Wound
Hypothalamus
2
1
4
3
Figure 15.15 One theoretical explanation for the production of fever in response to infection.
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Fever
• Continues as long as pyrogens are present
• Outcomes of fever
• Enhances effects of interferons
• Inhibits growth of some microbes
• May enhance the activities of phagocytes, cells of specific
immunity, and the process of tissue repair
© 2015 Pearson Education, Inc.
The Body's Second Line of Defense
• Tell Me Why
• Why are pathogen-associated molecular patterns
(PAMPs) necessary for Toll-like receptors (TLRs) to fully
function?
© 2015 Pearson Education, Inc.
© 2015 Pearson Education, Inc.
Important topics
• Body’s nonspecific lines of defense
• Macrophage name in the:
– Skin
– Brain
– Alveoli
– Liver
– Kidney
• Chemotaxis vs. diapedesis
• Complement system action
• Opsonization
• Granulocytes vs. agranulocytes
• Inflammatory response
• Anti-inflammatory action of Aspirin
• Mechanism of fever

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Microbiology Ch 15 lecture_presentation

  • 1. © 2015 Pearson Education, Inc. Chapter 15
  • 2. © 2015 Pearson Education, Inc. An Overview of the Body's Defenses • Resistance to most plant and animal pathogens • Species resistance • Due to physiological processes of humans that are incompatible with those of the pathogen • Correct chemical receptors are not present on human cells • Conditions may be incompatible with those needed for pathogen's survival • Humans do not have innate resistance to a number of pathogens
  • 3. © 2015 Pearson Education, Inc. An Overview of the Body's Defenses • Three main lines of defense • Innate immunity — first two lines of defense • External physical barriers to pathogens • Protective cells, bloodborne chemicals, and processes • Adaptive immunity
  • 4. © 2015 Pearson Education, Inc. Host Defenses: Overview
  • 5. © 2015 Pearson Education, Inc. An Overview of the Body's Defenses • Tell Me Why • Why aren't the body's skin and mucous membrane barriers significant factors in your resistance to infection by hyperthermophiles?
  • 6. © 2015 Pearson Education, Inc. The Body's First Line of Defense • Structures, chemicals, and processes that work to prevent pathogens entering the body • Skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems
  • 7. © 2015 Pearson Education, Inc. The Body's First Line of Defense • The Role of Skin in Innate Immunity • Skin is composed of two major layers • Epidermis • Multiple layers of tightly packed cells • Few pathogens can penetrate these layers • Shedding of dead skin cells removes microorganisms • Epidermal dendritic cells phagocytize pathogens • Dermis • Collagen fibers help skin resist abrasions that could introduce microorganisms
  • 8. © 2015 Pearson Education, Inc. Figure 15.1 A scanning electron micrograph of the surface of human skin.
  • 9. © 2015 Pearson Education, Inc. The Body's First Line of Defense • The Role of Skin in Innate Immunity • Skin has chemicals that defend against pathogens • Antimicrobial peptides (defensins) secreted by dermal cells • Perspiration secreted by sweat glands • Salt inhibits growth of pathogens • Antimicrobial peptides called dermcidins act against many bacteria and fungi • Lysozyme destroys cell wall of bacteria
  • 10. © 2015 Pearson Education, Inc. The Body's First Line of Defense • The Role of Skin in Innate Immunity • Skin has chemicals that defend against pathogens • Sebum secreted by sebaceous (oil) glands • Helps keep skin pliable and less likely to break or tear • Lowers skin pH to a level inhibitory to many bacteria
  • 11. © 2015 Pearson Education, Inc. The Body's First Line of Defense • The Role of Mucous Membranes in Innate Immunity • Mucous membranes line all body cavities open to environment • Two distinct layers • Epithelium • Thin, outer covering of the mucous membranes • Epithelial cells are living • Tightly packed to prevent entry of many pathogens • Continual shedding of cells carries away microorganisms • Dendritic cells below epithelium phagocytize pathogens • Goblet and ciliated columnar cells help remove invaders • Deeper connective layer that supports the epithelium • Produce chemicals that defend against pathogens
  • 12. © 2015 Pearson Education, Inc. Nasal cavity Pharynx Tongue Epiglottis Larynx (voice box) Esophagus Trachea Bronchus Bronchioles Figure 15.2 The structure of the respiratory system, which is lined with a mucous membrane.
  • 13. © 2015 Pearson Education, Inc.
  • 14. © 2015 Pearson Education, Inc. The Body's First Line of Defense • The Role of the Lacrimal Apparatus in Innate Immunity • Lacrimal apparatus • Produces and drains tears • Blinking spreads tears and washes surface of the eye • Lysozyme in tears destroys bacteria
  • 15. © 2015 Pearson Education, Inc. Nasolacrimal duct Lacrimal apparatus Lacrimal glands Lacrimal gland duct Lacrimal canal Nasolacrimal duct Paranasal sinus Pharynx Trachea Esophagus Lateral viewAnterior view Figure 15.3 The lacrimal apparatus.
  • 16. © 2015 Pearson Education, Inc. The Body's First Line of Defense • The Role of Normal Microbiota in Innate Immunity • Microbial antagonism • Normal microbiota compete with potential pathogens • Activities of normal microbiota make it hard for pathogens to compete • Consume nutrients • Create an environment unfavorable to other microorganisms • Help stimulate the body's second line of defense • Promote overall health by providing vitamins to host
  • 17. © 2015 Pearson Education, Inc. The Body's First Line of Defense • Other First-Line Defenses • Antimicrobial peptides • Present in skin, mucous membranes, neutrophils • Act against a variety of microbes • Work in several ways • Other processes and chemicals • Many organs secrete chemicals with antimicrobial properties
  • 18. © 2015 Pearson Education, Inc.
  • 19. © 2015 Pearson Education, Inc.
  • 20. © 2015 Pearson Education, Inc. The Body's First Line of Defense • Tell Me Why • Some strains of Staphylococcus aureus produce exfoliative toxin, a chemical that causes portions of the entire outer layer of the skin to be sloughed off in a disease called scalded skin syndrome. Given that cells of the outer layer are going to fall off anyway, why is this disease dangerous?
  • 21. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Operates when pathogens penetrate the skin or mucous membranes • Composed of cells, antimicrobial chemicals, and processes • Many of these components are contained or originate in the blood
  • 22. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Defense Components of Blood • Plasma • Mostly water containing electrolytes, dissolved gases, nutrients, and proteins • Serum is the fluid remaining when clotting factors are removed • Contains iron-binding compounds • Iron is needed for metabolism • Some microbes produce iron-binding proteins (siderophores) • Complement proteins and antibodies are also found in plasma
  • 23. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Defense Components of Blood • Defensive blood cells: leukocytes • Cells and cell fragments in plasma are called formed elements • Three types of formed elements • Erythrocytes • Carry oxygen and carbon dioxide in the blood • Platelets • Involved in blood clotting • Leukocytes • Involved in defending the body against invaders • Classified as granulocytes and agranulocytes
  • 24. © 2015 Pearson Education, Inc. Leukocytes Adaptive immunityGas transportation Innate immunity, second line of defense PhagocytosisInflammationClotting, inflammation Myeloid stem cell Lymphoid stem cell Erythroid stem cell Blood stem cell in bone marrow Erythrocyte Platelets Basophil Neutrophil Eosinophil Monocyte Lymphocyte Figure 15.4 A schematic representation of hematopoiesis.
  • 25. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Defense Components of Blood • Defensive blood cells: leukocytes • Granulocytes • Contain large granules that stain different colors • Three types • Basophils – stain blue with basic dye methylene blue • Eosinophils – stain red/orange with acidic dye eosin • Neutrophils – stain lilac with mix of acidic and basic dyes • Neutrophils and eosinophils • Phagocytize pathogens • Capable of diapedesis
  • 26. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Defense Components of Blood • Defensive blood cells: leukocytes • Agranulocytes • Cytoplasm appears uniform under a light microscope • Two types • Lymphocytes • Most involved in adaptive immunity • Natural killer lymphocytes • Monocytes • Leave the blood and mature into macrophages • Phagocytic cells that devour foreign objects
  • 27. © 2015 Pearson Education, Inc. Basophil 0.5–1% Eosinophil 2–4% Neutrophil 60–70% Lymphocyte 20–25% Monocyte 3–8% Granulocytes Agranulocytes Figure 15.5 Leukocytes as seen in stained blood smears.
  • 28. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Defense Components of Blood • Defensive blood cells: leukocytes • Lab analysis of leukocytes • Differential white blood cell count can signal disease • Increased eosinophils indicate allergies or parasitic worm infection • Bacterial diseases often show increase in leukocytes and neutrophils • Viral infections show increase in lymphocytes
  • 29. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Phagocytosis • Cells capable of phagocytosis are called phagocytes • Phagocytosis is not completely understood • Can be divided into six stages • Chemotaxis • Adherence • Ingestion • Maturation • Killing • Elimination
  • 30. © 2015 Pearson Education, Inc. Phagocytosis: Overview
  • 31. © 2015 Pearson Education, Inc. Chemotaxis of phagocyte to microbes Neisseria (microbes) Pseudopodia move (chemotaxis) Adherence Ingestion of microbes by phagocytes Fusion of a series of vesicles, including lysosomes Phagosome Killing of microbes by enzymes and other chemicals Elimination by exocytosis Residual body Phagolysosome Nucleus Lysosome Golgi body Phagocyte Pseudopod 2 1 3 4 5 6 Figure 15.6 The events in phagocytosis.
  • 32. © 2015 Pearson Education, Inc. Phagocytosis: Mechanism
  • 33. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Nonphagocytic Killing • Killing by eosinophils • Attack parasitic helminths by attaching to their surface • Secrete toxins that weaken or kill the helminth • Eosinophilia is often indicative of a helminth infestation or allergies • Eosinophil mitochondrial DNA and proteins form structure that kills some bacteria
  • 34. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Nonphagocytic Killing • Killing by natural killer lymphocytes • Secrete toxins onto surface of virally infected cells and tumors • Differentiate normal body cells because they have membrane proteins similar to the NK cells
  • 35. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Nonphagocytic Killing • Killing by neutrophils • Can destroy microbes without phagocytosis • Produce chemicals that kill nearby invaders • Generate extracellular fibers called neutrophil extracellular traps (NETs) that bind to and kill bacteria
  • 36. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Nonspecific Chemical Defenses Against Pathogens • Toll-like receptors (TLRs) • Integral membrane proteins produced by phagocytic cells • Bind pathogen-associated molecular patterns (PAMPs) • Initiate defensive responses • Apoptosis • Secretion of inflammatory mediators • Stimulate adaptive immune response
  • 37. © 2015 Pearson Education, Inc.
  • 38. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Nonspecific Chemical Defenses Against Pathogens • NOD proteins • Cytosolic proteins that bind PAMPs • Trigger inflammation, apoptosis, and other innate responses • Mechanism of action still being researched • Mutations in NOD genes associated with some inflammatory bowel diseases
  • 39. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Nonspecific Chemical Defenses Against Pathogens • Interferons • Protein molecules released by host cells to nonspecifically inhibit the spread of viral infections • Cause many symptoms associated with viral infections • Two types • Types I (alpha and beta) • Type II (gamma)
  • 40. © 2015 Pearson Education, Inc. Binding triggers transcription and translation of inactive antiviral proteins (AVPs). Same neighboring cell now protected at the later time Active AVPs degrade mRNA and bind to ribosomes, which stops protein synthesis and viral replication. When the second cell becomes infected with viruses, double- stranded RNA of the virus activates AVP. Meanwhile, the infected cell dies, releasing viruses. Interferon is released, diffuses to neighboring uninfected cells, and binds to receptors. Viral replication in cell triggers transcription and translation of IFN-α or IFN-β, depending on type of host cell. mRNA Inactive AVPs Uninfected neighboring cell Infected cell Interferon receptor IFN gene Double- stranded RNA Virus Virus infects cell. Nucleus mRNA IFN Infected cell at a later time Time passes mRNA Inactive AVP Double- stranded viral RNA Active AVPs Time passes Ribosome AVP gene 1 2 5 3 4 7 6 Figure 15.7 The actions of alpha and beta interferons.
  • 41. © 2015 Pearson Education, Inc.
  • 42. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Nonspecific Chemical Defenses Against Pathogens • Complement • Set of serum proteins designated numerically according to their order of discovery • Complement activation results in lysis of the foreign cell • Indirectly trigger inflammation and fever • Complement can be activated in three ways • Classical pathway • Alternative pathway • Lectin pathway
  • 43. © 2015 Pearson Education, Inc. Complement: Overview
  • 44. © 2015 Pearson Education, Inc. Membrane attack complex and cell lysis Inflammation C5 convertase C5 C5a + C5b Opsonization Inflammation Activation (C3 C3a + C3b) Complement cascade Complement proteins 1, 2, 4 Factors B, D, and P C3b Antibody Lectins Endotoxin and glycoproteins C3bAntigen Mannose Lectin pathwayAlternative pathwayClassical pathway Figure 15.8 Pathways by which complement is activated.
  • 45. © 2015 Pearson Education, Inc. Membrane attack complex Cytoplasmic membrane C5b combines with C6, C7, C8, and several molecules of C9 to form a membrane attack complex (MAC). A MAC drills a circular hole in the pathogen’s cytoplasmic membrane, leading to lysis of the cell. Causes chemotaxis of phagocytes and triggers inflammation Pathogen Antigen Antibody C1 becomes an active enzyme when it binds to antibody-antigen complexes. Enzyme C1 splits molecules of C2 and of C4. C3b combines with the remaining fragments of C2 and C4 to form a third enzyme. Fragments of C2 and C4 combine to form a second enzyme that splits C3 into C3a and C3b. Causes chemotaxis of phagocytes and triggers inflammation This enzyme cleaves C5 into C5a and C5b. Causes inflammation Acts as opsonin Enzymatic C1 H2O H2O H2O C9 C9C9 C9 C9 C9 C9 C9 C9 C9 C8 C7 C6C5b H2O C5b C5a1 2 3 4 5 6 Figure 15.9 The classical pathway and complement cascade.
  • 46. © 2015 Pearson Education, Inc. Membrane attack complex Figure 15.10 Membrane attack complexes.
  • 47. © 2015 Pearson Education, Inc. Complement: Activation
  • 48. © 2015 Pearson Education, Inc. Complement: Results
  • 49. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Nonspecific Chemical Defenses Against Pathogens • Complement • Inactivation of complement • Body's own cells withstand complement cascade • Proteins on many cells bind and break down activated complement proteins
  • 50. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Inflammation • Nonspecific response to tissue damage from various causes • Characterized by redness, heat, swelling, and pain • Two types • Acute • Chronic
  • 51. © 2015 Pearson Education, Inc. Inflammation: Overview
  • 52. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Inflammation • Acute inflammation • Develops quickly and is short lived • Is typically beneficial • Is important in the second line of defense • Dilation and increased permeability of the blood vessels • Migration of phagocytes • Tissue repair • Chronic inflammation • Long-lasting • Damage to tissues can cause disease
  • 53. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Inflammation • Dilation and increased permeability of blood vessels • Initial response to injury or invasion of pathogens • Release of inflammatory mediators triggers dilation of blood vessels • Bradykinin • Prostaglandins • Leukotrienes • Histamine • Signs and symptoms of inflammation can be blocked with antihistamines or antiprostaglandins
  • 54. © 2015 Pearson Education, Inc. Granule containing chemicals Inflammatory mediators C3a C5a C5a C3a Figure 15.11 The stimulation of inflammation by complement.
  • 55. © 2015 Pearson Education, Inc. Mediator Blood flow Dilated capillaries After Venule Capillaries BeforeArteriole Blood flow Figure 15.12 The dilating effect of inflammatory mediators on small blood vessels.
  • 56. © 2015 Pearson Education, Inc. Monocyte squeezing through interstitial space (diapedesis) More fluidSmall amount of fluid Monocyte More fluid and antimicrobial chemicals Interstitial spaces Small amount of fluidVenule wall Normal permeability of venule Increased permeability of venule during inflammation Figure 15.13 Increased vascular permeability during inflammation.
  • 57. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Inflammation • Migration of phagocytes • Increased blood flow delivers leukocytes to site of infection • Attach to receptors lining vessels via margination • Squeeze between vessel's walls • Attracted to site of infection by chemotactic factors • Neutrophils arrive first, followed by monocytes
  • 58. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Inflammation • Tissue repair • Final stage of inflammation • Delivers extra nutrients and oxygen to site • Some sites cannot be fully repaired and form scar tissue
  • 59. © 2015 Pearson Education, Inc. Bacteria A cut penetrates the epidermis barrier, and bacteria invade. Damaged cells release prostaglandins, leukotrienes, and histamine (shown in green here). Increased permeability allows antimicrobial chemicals and clotting proteins to seep into damaged tissue but also results in swelling, pressure on nerve endings, and pain. Nerve ending HeatSwelling Prostaglandins and leukotrienes make vessels more permeable. Histamine causes vasodilation, increasing blood flow to the site. Macrophages and neutrophils squeeze through walls of blood vessels (diapedesis). Blood clot forms. More phagocytes migrate to the site and devour bacteria. Accumulation of damaged tissue and leukocytes forms pus. Undifferentiated stem cells repair the damaged tissue. Blood clot is absorbed or falls off as a scab. 1 2 5 3 4 6 7 8 9 Figure 15.14 An overview of the events in inflammation following a cut and infection.
  • 60. © 2015 Pearson Education, Inc.
  • 61. © 2015 Pearson Education, Inc. Inflammation: Steps
  • 62. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Fever • Body temperature over 37°C • Results when pyrogens trigger the hypothalamus to increase the body's core temperature • Various types of pyrogens • Bacterial toxins • Cytoplasmic contents of bacteria released by lysis • Antibody-antigen complexes • Pyrogens released by phagocytes that have phagocytized bacteria • Exact mechanism of fever is not known
  • 63. © 2015 Pearson Education, Inc. Hypothalamus secretes prostaglandin, which resets hypothalamic thermostat. Nerve impulses cause shivering, higher metabolic rate, inhibition of sweating, and vasoconstriction. These processes increase body temperature to the point set by the hypothalamic thermostat. Chemicals secreted by phagocytes travel in blood to hypothalamus. Wound Hypothalamus 2 1 4 3 Figure 15.15 One theoretical explanation for the production of fever in response to infection.
  • 64. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Fever • Continues as long as pyrogens are present • Outcomes of fever • Enhances effects of interferons • Inhibits growth of some microbes • May enhance the activities of phagocytes, cells of specific immunity, and the process of tissue repair
  • 65. © 2015 Pearson Education, Inc. The Body's Second Line of Defense • Tell Me Why • Why are pathogen-associated molecular patterns (PAMPs) necessary for Toll-like receptors (TLRs) to fully function?
  • 66. © 2015 Pearson Education, Inc.
  • 67. © 2015 Pearson Education, Inc. Important topics • Body’s nonspecific lines of defense • Macrophage name in the: – Skin – Brain – Alveoli – Liver – Kidney • Chemotaxis vs. diapedesis • Complement system action • Opsonization • Granulocytes vs. agranulocytes • Inflammatory response • Anti-inflammatory action of Aspirin • Mechanism of fever