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CHAPTER
16
Innate
Immunity:
Nonspecific
Defenses of
the Host
© 2016 Pearson Education, Ltd.
Big Picture: Immunity
© 2016 Pearson Education, Ltd.
Big Picture: Immunity
© 2016 Pearson Education, Ltd.
Big Picture: Immunity
• White blood cell (WBC) counts measure
leukocytes in the blood
• High WBC counts may indicate bacterial infections,
autoimmune diseases, or side effects of
medications
• Low WBC counts may indicate viral infections,
pneumonia, autoimmune diseases, or cancers
© 2016 Pearson Education, Ltd.
Big Picture: Immunity
NORMAL RANGES AND PERCENTAGES
for men and nonpregnant women
White blood cell count:
5,000–10,000 WBCs per cubic millimeter
(mm3) or 5.0–10.0 x 109 WBCs per liter.
Plasma
White
blood cells
Red blood
cells
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Neutrophils: 60% to 70%
Lymphocytes: 20% to 25%
Monocytes: 3% to 8%
Eosinophils: 2% to 4%
Basophils: 0.5% to 1%
The Concept of Immunity
 Immunity: ability to ward off disease.
 Innate (nonspecific) immunity: defenses against any
pathogen and are present at birth.
 Adaptive (specific) immunity: defenses that involve
specific recognition of a microbe once it has breached
the innate immunity defenses.
 Susceptibility: lack of resistance to a disease.
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 Toll-like receptors (TLRs) on host cells attach to
pathogen-associated molecular patterns (PAMPs).
 TLRs bound to PAMPs induce the release of cytokines
from the host cell that regulate the intensity and
duration of immune responses.
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First line of defense: skin and mucous membrane
Physical Factors
 Skin: the largest organ of human body in terms of
surface area.
 Dermis: inner portion made of connective tissue
 Epidermis: outer portion made of tightly packed epithelial
cells containing keratin, a protective protein
Figure 16.1 A section through human skin.
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 Mucous membranes: consist of an epithelial layer and
an underlying connective tissue layer
 Lacrimal apparatus (淚器): Washes eye.
Figure 16.2 The lacrimal apparatus.
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 Ciliary escalator: microbes trapped in mucus are
transported away from the lungs.
Figure 16.3 The ciliary escalator.
 Earwax: prevents microbes from entering the ear.
 Urine: flows out.
 Vaginal secretions: flow out.
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Chemical Factors
 Sebum (油脂):
 produced by sebaceous (oil) glands of the skin
 one of the components is unsaturated fatty acids, which inhibit
the grow of certain pathogenic bacteria and fungi
 low pH (3-5) is caused in partly by fatty acid and lactic acid
 Perspiration (汗):
 produced by sweat glands of the skin
 contain lysozyme
 can break peptidoglycan of cell walls of gram (+) bacteria and
less gram (-) bacteria
 is also found in tears, saliva, nasal secretions, tissue fluids
 Low pH (1.2-3.0) of gastric juice.
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Normal Microbiota and Innate Immunity
 Microbial antagonism/competitive exclusion: Normal
microbiota compete with pathogens.
 For example: (in Ch14)
 Normal microbiota vs Candida albicans in vagina
 E. coli vs Salmonella and Shigella in large intestine
 Normal microbiota vs Clostridium difficiles in large
intestine
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Second line of defense
Formed Elements in Blood
 Cells and cell fragments suspended in plasma.
 Erythrocytes (red blood cells)
 Leukocytes (white blood cells)
 Platelets
 Created in red bone marrow stem cells via
hematopoiesis.
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Figure 16.4 Hematopoiesis.
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 Leukocytes are divided into:
 Granulocytes:
 Neutrophils: highly phagocytic and motile
• commonly called polymorphonuclear leukocytes (PMNs), or
polymorphs
• activate in the initial stage of an infection
 Basophils: produce histamine
• important in inflammation and allergic response
 Eosinophils: produce toxic proteins against parasites and some
phagocytosis
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Table 16.1 Leukocytes (White Blood Cells)
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 Agranulocytes are leukocytes with granules in their
cytoplasm that are not visible with a light microscope.
 Monocytes: mature into macrophages in tissues where
they are phagocytic
 Dendritic cells: found in the skin, mucous membranes,
and thymus; phagocytic
 Lymphocytes: T cells, B cells, and NK cells; play a role in
adaptive immunity
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 Agranulocytes:
 Monocytes:
• are not actively phagocytic until they leave circulating blood
and mature macrophages
• fixed macrophages (or histiocytes) are found in lungs, liver,
and bronchi etc
• wandering macrophages roam the tissues
 Dendritic cells:
• are belived to be derived from monocytes
• abundant in the epidermis of the skin, mucous membranes,
the thymus and lymph nodes
• initiate adaptive immune response
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 Lymphocytes: include natural killer (NK) cells, T cells and B cells
NK
T
• NK cells are found in blood, spleen, lymph nodes, and red
bone marrow, and attack abnormal body cells by perforins
(穿孔素) and granzymes (顆粒溶解酶).
• B cells and T cells occur in lymphoid tissues of lymphoid
system and also circulate in the blood.
B
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Table 16.1 Leukocytes (White Blood Cells)
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The Lymphatic System
 The lymphatic system:
 Consists of lymph, lymphatic vessels, lymphoid tissue,
and red bone marrow.
 Contains lymphocytes and phagocytic cells.
 Lymph carries microbes to lymph nodes where
lymphocytes and macrophages destroy the pathogen.
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Figure 16.5 The lymphatic system.
Right
lymphatic duct
Tonsil
Thoracic (left
lymphatic) duct
Right
subclavian
vein
Left
subclavian
vein
Thymus
Lymph node
Thoracic duct
Spleen
Large intestine
Small intestine
Peyer’s patch
Lymphatic vessel
Red bone marrow
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Figure 16.6 Lymphatic capillaries.
Interstitial fluid
(between cells)
Venule
Tissue cell
Lymph in lymphatic
capillary
Arteriole
Lymphatic capillary
Blood capillary
Flow of fluid between arteriole, blood capillaries,
lymphatic capillaries, and venule
Lymph in lymphatic
capillary
Lymphatic capillary
One-way
opening
Interstitial fluid flow
Tissue cells
Lymphatic vessel
Toward lymph node
Lymphatic capillaries and lymphatic vein
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Phagocytosis
 Phago: from Greek, meaning
eat.
 Cyte: from Greek, meaning
cell.
 Fixed macrophages are
residents in tissues and
organs.
 Free (wandering)
macrophages roam tissues
and gather at sites of infection.
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Figure 16.7 A macrophage engulfing
rod-shaped bacteria.
The Mechanism of Phagocytosis
 Chemotaxis (趨化作用)
 Chemical signals attract phagocytes to microorganisms.
 Adherence
 Attachment of a phagocyte to the surface of the
microorganism.
 Ingestion
 Opsonization: microorganism is coated with serum
proteins, making ingestion easier.
 Digestion
 Microorganism is digested inside a phagolysosome.
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Figure 16.8 The Phases of Phagocytosis.
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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 burnetii
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Inflammation
 Damage to the body’s tissue triggers a defensive
response called inflammation.
 Inflammation is usually characterized by 4 signs and
symptoms:
 Redness
 Pain
 Heat
 Swelling (edema)
 Loss of function (  the fifth)
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 Inflammation has the following function:
 to destroy the injurious agent, if possible, and to remove
it and its by-products from the body
 if destruction is not possible, to limit the effects on the
body by confining or walling off the injurious agent and its
by-products
 to repair or replace tissue damaged by the injurious
agent or its by-products
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
The process of inflammation into 3 stages:
1. Vasodilation and increased permeability of blood
vessels
2. Phagocyte migration and phagocytosis
3. Tissue repair
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Vasodilation and Increased Permeability of Blood
Vessels

During inflammation, there is an activation and
increased concentration of a group of proteins in the
blood called acute-phase proteins.
 Histamine
 Kinins
 Prostaglandins
 Leukotrienes
 Cytokines
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Figure 16.9a-b The process of inflammation.
Tissue damage
Bacteria
Blood
vessel
Nerve
Chemical
Function
Histamine
Vasodilation,
increased permeability
of blood vessels
Kinins
Vasodilation,
increased permeability
of blood vessels
Prostaglandins
Intensity histamine
and kinin effect
Leukotrienes
Increased permeability
of blood vessels,
phagocytic attachment
Epidermis
Dermis
Subcutaneous
tissue
Vascular reactions and phagocytosis
Chemicals such as histamine,
kinins, prostaglandins,
leukotrienes, and cytokines
(represented as blue dots) are
released by damaged cells.
Blood clot forms.
Abscess starts to form
(orange area).
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Phagocyte Migration and Phagocytosis
 Margination is the sticking of phagocytes to blood
vessels in response to cytokines at the site of
inflammation
 Phagocytes squeeze between endothelial cells of
blood vessels via diapedesis
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Figure 16.9b The process of inflammation.
Blood vessel
endothelium
Monocyte
Margination—phagocytes
stick to endothelium.
RBC
Bacterium
Diapedesis—phagocytes
squeeze between endothelial
cells.
Phagocytosis of
invading bacteria occurs.
Macrophage
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Neutrophil
Tissue Repair
 Cannot be completed until all harmful substances are
removed or neutralized
 Stroma is the supporting connective tissue that is
repaired
 Parenchyma is the functioning part of the tissue that is
repaired
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Figure 16.9c The process of inflammation.
(c) Tissue repair
Scab
Blood clot
Regenerated epidermis
(parenchyma)
Regenerated dermis
(stroma)
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Fever
 Abnormally high body temperature.
 Hypothalamus normally set at 37°C (98.6°F).
 Cytokines cause the hypothalamus to release
prostaglandins that reset the hypothalamus to a higher
temperature
 Body constricts the blood vessels, and shivering occurs
(which raises temperature)
 As body temperature falls (crisis), vasodilation and
sweating occurs
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 Advantages
Increase IL-1 activity
 Disadvantages
Tachycardia 心跳過快
Acidosis 酸中毒
Dehydration 脫水
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Antimicrobial Substances
The Complement System
 consisting of over 30 proteins
 produced by liver
 found circulating in blood serum
 destroy microbes by
 cytolysis
 inflammation
 phagocytosis ( opsonization)
 are inactive until they are split into fragments
 are numbered C1 through C9
 activated in a cascade
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 The cascade of complement proteins that occurs
during an infection is called complement activation.
 Complement activation may occur in 3 pathways:
 the classical pathway
 the alternative pathway
 the lectin pathway
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The Classical Pathway
 Antibodies bind to antigens, activating C1
 C1 splits and activates C2 and C4
 C2a and C4b combine and activate C3
 C3a functions in inflammation
 C3b functions in cytolysis and opsonization
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Figure 16.10a Pathways of complement activation.
pathway of complement activation
classical
Microbe
Antigen
Antibody
C1
C2
C2b
C4
C2a
C4b
C4a
C3
C3a
C3b
inflammation cytolysis opsonization
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The Alternative Pathway
 C3 present in the blood combines with factors B, D,
and P on microbe surface
 C3 splits into C3a and C3b, functioning the same as in
the classical pathway
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Figure 16.10b Pathways of complement activation.
alternative
Microbe
Lipid–
carbohydrate
complex
Microbe
B
D
P
Factors
C3
C3a
C3b
inflammation cytolysis opsonization
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The Lectin Pathway
 Macrophages ingest pathogens, releasing cytokines
that stimulate lectin production in the liver
 Mannose-binding lectin (MBL) binds to mannose,
activating C2 and C4
 C2a and C4b activate C3, which functions the same as
in the classical and alternative pathways
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Figure 16.10c Pathways of complement activation.
lectin
Microbe
Carbohydrate
containing
mannose
Mannose-binding
lectin (MBL)
C2
C2b
C4
C2a
C4b
C4a
C3
C3a
C3b
inflammation cytolysis opsonization
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Outcomes of Complement Activation
 Cytolysis
 Activated complement proteins create a membrane
attack complex (MAC)
 Opsonization (調理作用)
 Promotes attachment of a phagocyte to a microbe
 Inflammation
 Activated complement proteins bind to mast cells,
releasing histamine
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Figure 16.11 The MAC results in cytolysis.
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Figure 16.12 Outcomes of Complement Activation
outcomes of complement activation
C3
Splits into activated C3a and C3b
opsonization
cytolysis
C3a
C3b
C3a
inflammation
C3b
C3a
C3b
C5
C5a
C5
C5b
C5a
Histamine
C6
C7
C5b
C8
Microbe
C3a
receptor
C9
Channel
C5a
C3a
C3b protein
Mast cell
Microbes
C5a
receptor
Phagocytesa
C6
C7 C5b
C8
C9
Phagocyte
Microbes burst as extracellular
fluid flows in through transmembrane channel
formed by membrane attack complex.
Coating microbes with C3b
enhances phagocytosis.
Blood vessels become more
permeable, and chemotactic agents
attract phagocytes to area.
KEY CONCEPTS
The complement system is another way the body fights infection and destroys pathogens. This component of innate immunity
“complements” other immune reactions.
Complement is a group of over 30 proteins circulating in serum that are activated in a cascade: one complement protein triggers
the next.
The cascade can be activated by a pathogen directly or by an antibody–antigen reaction.
Together these proteins destroy microbes by (1) cytolysis, (2) enhanced phagocytosis, and (3) inflammation.
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Figure 16.13 Inflammation stimulated by complement.
C3a and C5a bound to mast
cell, basophils, and platelets
trigger the release of histamine
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C5a functions as a chemotactic
factor that attracts phagocytes
to the site of complement
activation
Regulation of complement
 Regulatory proteins readily break down complement
proteins, minimizing host cell destruction
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Complement and disease
 Lack of complement proteins causes susceptibility to
infections
Evading the complement system
 Capsules prevent complement activation
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Interferons (IFNs)
 IFN are a family of cytokines produced by cells; have
antiviral activity.
 Human IFNs are of 3 principal types:
 Alpha IFN (IFN-) and Beta IFN (IFN-): produced by
cells in response to viral infections; cause neighboring
cells to produce antiviral proteins (AVPs) that inhibit viral
replication.
 Gamma IFN (IFN-): causes neutrophils and
macrophages to phagocytize bacteria.
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Figure 16.14 Antiviral action of alpha and beta interferons (IFNs).
New viruses replicated
in host cell infect
neighboring cells.
Transcription Translation
Viral
RNA
Transcription Translation
Viral
RNA
Viral
RNA
Infecting
virus
Virus
replicates
Alpha
and beta
interferons
Nucleus
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Viral
replication
inhibited
IFN-mRNA
Virus-infected host cell
Viral RNA from
an infecting virus
enters the cell.
Antiviral
proteins
(AVPs)
The virus induces the host cell to
produce interferon mRNA
(IFN-mRNA), which is translated
into alpha and beta interferons.
Neighboring cell
Interferons make contact with uninfected
neighboring host cells, where they bind either
to the plasma membrane or to nuclear
receptors. Interferons induce the cells to
synthesize antiviral proteins (AVPs).
AVPs degrade viral mRNA and
inhibit protein synthesis—and
thus interfere with viral
replication.
Iron-binding proteins
 Transferrin (運鐵蛋白) is found in blood and tissue
fluids
 Lactoferrin (乳鐵蛋白) is found in milk, saliva, and
mucus
 Ferritin (含鐵蛋白) is found in the liver, spleen and
red bone marrow
 Hemoglobin is located within RBC
 Function: inhibit bacterial growth by reducing the
amount of available iron
siderophore
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Antimicrobial peptides (AMPs)
 Short peptides produced in response to protein and
sugar molecules on microbes
 Inhibit cell wall synthesis
 Form pores in the plasma membrane
 Broad spectrum of activity
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Table 16.2 Summary of Innate Immunity Defenses (1 of 2)
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Table 16.2 Summary of Innate Immunity Defenses (2 of 2)
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