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Chapter 16
Innate Immunity:
Nonspecific
Defenses of the
Host
© 2013 Pearson Education, Inc.
Copyright © 2013 Pearson Education, Inc.
Lectures prepared by Christine L. Case
Lectures prepared by Christine L. Case
Insert Fig CO 16
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Fever
 Advantages
 Increases transferrins
 Increases IL-1 activity
 Produces interferon
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 Disadvantages

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

Tachycardia
Acidosis
Dehydration
44–46°C fatal
The Concept of Immunity
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Susceptibility: lack of resistance to a disease
Immunity: ability to ward off disease
Innate immunity: defenses against any pathogen
Adaptive immunity: immunity or resistance to a
specific pathogen
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Figure 16.1 An overview of the body’s defenses.
First line of defense
• Intact skin
• Mucous membranes
and their secretions
• Normal microbiota
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Second line of defense
• Phagocytes, such as neutrophils,
eosinophils, dendritic cells, and
macrophages
• Inflammation
• Fever
• Antimicrobial substances
Third line of defense
• Specialized lymphocytes:
T cells and B cells
• Antibodies
The Concept of Immunity
 Host Toll-like receptors (TLRs) attach to
pathogen-associated molecular patterns
(PAMPs)
 TLRs induce cytokines that regulate the intensity
and duration of immune responses
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Physical Factors
 Skin
 Epidermis consists of tightly packed cells with
 Keratin, a protective protein
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Figure 16.2 A section through human skin.
Top layers
of epidermis
with keratin
Epidermis
Dermis
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Physical Factors
 Mucous membranes
 Mucus: traps microbes
 Ciliary escalator: transports microbes trapped in
mucus away from the lungs
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Figure 24.7 Ciliated cells of the respiratory system infected with Bordetella pertussis.
B. pertussis
Cilia
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Figure 16.4 The ciliary escalator.
Trapped
particles
in mucus
Cilia
Goblet cells
Insert Fig 16.4
Ciliated cells
Computer-enhanced
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Physical Factors
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Lacrimal apparatus: washes eye
Saliva: washes microbes off
Urine: flows out
Vaginal secretions: flow out
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Figure 16.3 The lacrimal apparatus.
Lacrimal glands
Upper eyelid
Lacrimal canal
Nasolacrimal
duct
Nose
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Chemical Factors
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Fungistatic fatty acid in sebum
Low pH (3–5) of skin
Lysozyme in perspiration, tears, saliva, and urine
Low pH (1.2–3.0) of gastric juice
Low pH (3–5) of vaginal secretions
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Normal Microbiota and Innate
Immunity
 Microbial antagonism/competitive exclusion:
normal microbiota compete with pathogens or
alter the environment
 Commensal microbiota: one organism (microbe)
benefits, and the other (host) is unharmed
 May be opportunistic pathogens
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Table 16.1 Formed Elements in Blood (Part 1 of 2)
Insert Table 16.1
If possible, break into multiple slides
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Table 16.1 Formed Elements in Blood (Part 2 of 2)
Insert Table 16.1
If possible, break into multiple slides
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Differential White Cell Count
 Percentage of each type of white cell in a sample of
100 white blood cells
Neutrophils
60–70%
Basophils
0.5–1%
Eosinophils
2–4%
Monocytes
3–8%
Lymphocytes
20–25%
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Figure 16.5a The lymphatic system.
Right
lymphatic
duct
Right
subclavian
vein
Thoracic
(left
lymphatic)
duct
Left
subclavian
vein
Tonsil
Thymus
Heart
Thoracic duct
Spleen
Lymphatic vessel
Small intestine
Large intestine
Red
bone marrow
(a) Components of lymphatic system
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Peyer’s patch
Lymph node
Figure 16.5b-c The lymphatic system.
Venule
Interstitial fluid
Blood capillary
Tissue cell
Blood
One-way opening
Arteriole
Blood
Lymphatic capillary
Interstitial
fluid (between cells)
Lymph
Tissue cell
Lymphatic capillary
Relationship of lymphatic capillaries to
tissue cells and blood capillaries
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Lymph
Details of a lymphatic capillary
Phagocytosis
 Phago: from Greek, meaning eat
 Cyte: from Greek, meaning cell
 Ingestion of microbes or particles by a cell,
performed by phagocytes
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Figure 16.6 A macrophage engulfing rod-shaped bacteria.
Macrophage
Bacterium
Pseudopods
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Phagocytosis
 Neutrophils
 Fixed macrophages
 Wandering macrophages
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Figure 16.7 The Phases of Phagocytosis.
A phagocytic
macrophage uses a
pseudopod to engulf
nearby bacteria.
Pseudopods
Phagocyte
Cytoplasm
1 CHEMOTAXIS
and
ADHERENCE
of phagocyte to
microbe
2 INGESTION
of microbe by phagocyte
4 Fusion of phagosome
with a lysosome
to form a phagolysosome
Microbe
or other
particle
Details of
adherence
3 Formation of phagosome
(phagocytic vesicle)
Lysosome
PAMP
(peptidoglycan
in cell wall)
Digestive
enzymes
Partially
digested
microbe
5 DIGESTION
of ingested
microbes by
enzymes in the
phagolysosome
Indigestible
material
6 Formation of
the residual body
containing
indigestible
material
TLR
(Toll-like receptor)
Plasma membrane
7 DISCHARGE of
waste materials
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Oxidative Burst
4 Superoxide dismutase converts
superoxide to hydrogen
peroxide (H2O2)
5 H2O2 burst
kills bacterium
3 NADPH oxidase
1 Bacterium adheres
to membrane of
neutrophil Insert art from Clinical Case on
Superoxide
p. 463
dismutase
O2 •
H2O2
Plasma
membrane
Neutrophil
uses electron from
NADPH to produce
superoxide (O2 •)
O2
If possible on this slide, include title:
Oxidative Burst
NADPH
oxidase
Pentose
phosphate
pathway
NADP+
2 NADPH is produced
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NADPH
Microbial Evasion of Phagocytosis
Inhibit adherence:
M protein, capsules
Streptococcus pyogenes, S. pneumoniae
Kill phagocytes: Leukocidins
Staphylococcus aureus
Lyse phagocytes:
Membrane attack complex
Listeria monocytogenes
Escape phagosome
Shigella, Rickettsia
Prevent phagosome–
lysosome fusion
HIV, Mycobacterium tuberculosis
Survive in phagolysosome
Coxiella burnettii
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Inflammation
 Activation of acute-phase proteins (complement,
cytokine, and kinins)
 Vasodilation (histamine, kinins, prostaglandins,
and leukotrienes)
 Redness
 Swelling (edema)
 Pain
 Heat
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Chemicals Released by Damaged Cells
Histamine
Vasodilation, increased permeability
of blood vessels
Kinins
Vasodilation, increased permeability
of blood vessels
Intensify histamine and kinin effect
Prostaglandins
Leukotrienes
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Increased permeability of blood vessels,
phagocytic attachment
Figure 16.8a-b The process of inflammation.
Bacteria entering
on knife
Bacteria
Epidermis
Blood vessel
Dermis
Nerve
Subcutaneous
tissue
(a) Tissue damage
1 Chemicals such as histamine, kinins,
prostaglandins, leukotrienes, and
cytokines (represented as blue
dots) are released by
damaged cells.
2 Blood clot forms.
3 Abscess starts to form
(orange area).
(b) Vasodilation and increased
permeability of blood vessels
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Figure 16.8c The process of inflammation.
Blood vessel
endothelium
Monocyte
4 Margination—
phagocytes stick
to endothelium.
5 Diapedesis—
phagocytes
squeeze
between
endothelial cells.
Insert Fig 16.8c
6 Phagocytosis of
invading bacteria occurs.
Red
blood
cell
Macrophage
(c) Phagocyte migration
and phagocytosis
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Bacterium
Neutrophil
Figure 16.8d The process of inflammation.
Scab
Blood clot
Regenerated
epidermis
(parenchyma)
Insert Fig 16.8d
(d) Tissue repair
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Regenerated
dermis
(stroma)
Fever
 Abnormally high body temperature
 Hypothalamus is normally set at 37°C
 Gram-negative endotoxins cause phagocytes to
release interleukin-1 (IL-1)
 Hypothalamus releases prostaglandins that reset
the hypothalamus to a high temperature
 Body increases rate of metabolism, and shivering
occurs, which raise temperature
 Vasodilation and sweating: body temperature falls
(crisis)
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The Complement System
 Serum proteins activated in a cascade
 Activated by
 Antigen–antibody reaction
 Proteins C3, B, D, P and a pathogen
ANIMATION Complement: Overview
ANIMATION Complement: Activation
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The Complement System
 C3b causes opsonization
 C3a + C5a cause inflammation
 C5b + C6 + C7 + C8 + C9 cause cell lysis
ANIMATION Complement: Results
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Figure 16.9 Outcomes of Complement Activation.
1 Inactivated C3 splits into activated
C3
C3a and C3b.
2 C3b binds to microbe, resulting
in opsonization.
C3b
C3a
C3b
proteins
3 C3b also splits C5
into C5a and C5b
5 C3a and C5a cause
mast cells to release
histamine, resulting
in inflammation;
C5a also attracts
phagocytes.
opsonization
C5
Enhancement of phagocytosis
by coating with C3b
C5a
C5b
Histamine
C5a
Insert Fig 16.9
Mast cell
4 C5b, C6, C7, and C8 bind
together sequentially and
insert into the microbial
plasma membrane, where
they function as a receptor
to attract a C9 fragment;
additional C9 fragments are
added to form a channel.
Together, C5b through C8
and the multiple C9
fragments form the
membrane attack complex,
resulting in cytolysis.
C5a receptor
C6
C3a receptor
C3a
inflammation
C7
C8
Increase of blood vessel
permeability and chemotactic
attraction of phagocytes
C9
Microbial
plasma
membrane
Channel
C6
C7
C5b
C8
C9
Formation of membrane
attack complex (MAC)
C6
C5b
C7
C8
C9
Cytolysis
cytolysis
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Bursting of microbe due to inflow of extracellular fluid through
transmembrane channel formed by membrane attack complex
Effects of Complement Activation
 Opsonization, or immune adherence: enhanced
phagocytosis
 Membrane attack complex: cytolysis
 Attract phagocytes
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Figure 16.10 Cytolysis caused by complement.
Insert Fig 16.10
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Figure 16.11 Inflammation stimulated by complement.
C5a
C5a receptor
Histamine
Phagocytes
Neutrophil
Histaminecontaining
granule
Insert Fig 16.11
Histaminereleasing
mast cell
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C3a
C3a receptor
C5a
Macrophage
Figure 16.12 Classical pathway of complement activation.
Microbe
Antigen
C1 is activated
by binding to
antigen–antibody
complexes.
Antibody
C1
Activated C1 splits
C2 into C2a and
C2b, and C4 into
C4a and C4b.
C4
C2
Insert Fig 16.12
C2b
C2a
C2a and C4b combine
and activate C3,
splitting
it into C3a and C3b
(see also Figure 16.9).
Opsonization
C4a
C3
C3b
Cytolysis
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C4b
C3a
Inflammation
Figure 16.13 Alternative pathway of complement activation.
Lipid-carbohydrate
complex
Microbe
C3 combines with
factors B, D, and P
on the surface of
a microbe.
B
D
P
C3
Insert Fig 16.13
This causes C3 to
split into fragments
C3a and C3b.
C3b
C3a
Inflammation
Opsonization
Cytolysis
Key:
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B B factor
D D factor
P P factor
Figure 16.14 The lectin pathway of complement activation.
Microbe
Carbohydrate
containing
mannose
Lectin
Lectin binds to
an invading cell.
Bound lectin
splits C2 into
C2b and C2a
and C4 into
C4b and C4a.
C2
C2b
C4
C2a and C4b combine
and activate C3
(see also Figure 16.9).
Opsonization
C4b
C2a
C3
C3b
Cytolysis
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C4a
C3a
Inflammation
Some Bacteria Evade Complement
 Capsules prevent C activation
 Surface lipid–carbohydrate complexes prevent
formation of membrane attack complex (MAC)
 Enzymatic digestion of C5a
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Interferons (IFNs)
 IFN- and IFN-: cause cells to produce antiviral
proteins that inhibit viral replication
 IFN-: causes neutrophils and macrophages
to phagocytize bacteria
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Figure 16.15 Antiviral action of alpha and beta interferons (IFNs).
1
Viral RNA from
an infecting virus
enters the cell.
2 The infecting virus
5 New viruses released by
replicates into
new viruses.
Viral RNA
the virus-infected host
cell infect neighboring
host cells.
3 The infecting virus
also induces the
host cell to produce
interferon mRNA
(IFN-mRNA), which
is translated into
alpha and beta
interferons.
Infecting
virus
Viral RNA
Nucleus
Translation
Insert Fig 16.15
Transcription
Transcription
IFN-mRNA
4 Interferons released by the
virus-infected host cell bind
to plasma membrane or
nuclear membrane receptors
on uninfected neighboring
host cells, inducing them to
synthesize antiviral proteins
(AVPs). These include
oligoadenylate synthetase
and protein kinase.
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Alpha
and beta
interferons
Translation
Virus-infected
host cell
Neighboring host cell
Antiviral
proteins
(AVPs)
6 AVPs degrade
viral mRNA and
inhibit protein
synthesis—and
thus interfere
with viral
replication.
Innate Immunity
 Transferrins
 Bind serum iron
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 Antimicrobial peptides
 Lyse bacterial cells