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CHAPTER
16
Innate
Immunity:
Nonspecific
Defenses of
the Host
© 2016 Pearson Education, Inc.
© 2016 Pearson Education, Inc.
Big Picture: Immunity
© 2016 Pearson Education, Inc.
Big Picture: Immunity
© 2016 Pearson Education, Inc.
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, Inc.
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
Learning Objectives
16-1 Differentiate innate and adaptive immunity.
16-2 Define Toll-like receptors.
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The Concept of Immunity
• Immunity: ability to ward off disease
• Susceptibility: lack of resistance to a disease
• Innate immunity: defenses against any pathogen;
rapid, present at birth
• Adaptive immunity: immunity or resistance to a
specific pathogen; slower to respond, has memory
component
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The Concept of Immunity
• 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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Host Defenses: The Big Picture
PLAY
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Animation: Host Defenses: The Big Picture
Check Your Understanding
 Which defense system, innate or adaptive
immunity, prevents entry of microbes into the
body?
16-1
 What relationship do TLRs have to pathogenassociated molecular patterns?
16-2
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First Line of Defense: Skin and Mucous
Membranes
Learning Objectives
16-3 Describe the role of the skin and mucous
membranes in innate immunity.
16-4 Differentiate physical from chemical factors,
and list five examples of each.
16-5 Describe the role of normal microbiota in
innate immunity.
© 2016 Pearson Education, Inc.
Physical Factors
• Skin
• Dermis: inner portion made of connective tissue
• Epidermis: outer portion made of tightly packed
epithelial cells containing keratin, a protective protein
• Shedding and dryness of skin inhibits microbial
growth
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Figure 16.1 A section through human skin.
Top layers
of epidermis
with keratin
Epidermis
Dermis
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Physical Factors
• Mucous membranes
• Epithelial layer that lines the gastrointestinal,
respiratory, and genitourinary tracts
• Mucus: viscous glycoproteins that trap microbes and
prevent tracts from drying out
• Lacrimal apparatus: drains tears; washes eye
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Figure 16.2 The lacrimal apparatus.
Lacrimal glands
Upper eyelid
Lacrimal canal
Nasolacrimal
duct
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Physical Factors
• Ciliary escalator transports microbes trapped in
mucus away from the lungs
• Earwax prevents microbes from entering the ear
• Urine cleans the urethra via flow
• Vaginal secretions move microorganisms out of
the vaginal tract
• Peristalsis, defecation, vomiting, diarrhea
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Figure 16.3 The ciliary escalator.
Trapped
particles
in mucus
Cilia
Goblet cells
Ciliated cells
Computer-enhanced
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Chemical Factors
• Sebum forms a protective film and lowers the pH
(3–5) of skin
• Lysozyme in perspiration, tears, saliva, and urine
destroys bacterial cell walls
• Low pH (1.2–3.0) of gastric juice destroys most
bacteria and toxins
• Low pH (3–5) of vaginal secretions inhibit
microbes
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Normal Microbiota and Innate Immunity
• Normal microbiota compete with pathogens via
microbial antagonism
• Produce substances harmful to pathogens
• Alter conditions that affect pathogen survival
• Commensalism: one organism benefits while the
other (host) is unharmed
• Probiotics: live microbial cultures administered to
exert a beneficial effect
© 2016 Pearson Education, Inc.
Check Your Understanding
 Identify one physical factor and one chemical factor that
prevent microbes from entering the body through skin and
mucous membranes.
16-3
 Identify one physical factor and one chemical factor that
prevent microbes from entering or colonizing the body
through the eyes, digestive tract, and respiratory tract.
16-4
 Distinguish microbial antagonism from commensalism.
16-5
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Second Line of Defense
Learning Objectives
16-6 Classify leukocytes, and describe the roles of
granulocytes and monocytes.
16-7 Describe the eight different types of WBCs,
and name a function for each type.
16-8 Differentiate the lymphatic and blood
circulatory systems.
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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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Formed Elements in Blood
• Granulocytes are leukocytes with granules in
their cytoplasm that are visible with a light
microscope
• Neutrophils: phagocytic; work in early stages of
infection
• Basophils: release histamine; work in allergic
responses
• Eosinophils: phagocytic; toxic against parasites and
helminths
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Table 16.1 Leukocytes (White Blood Cells)
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Formed Elements in Blood
• 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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Table 16.1 Leukocytes (White Blood Cells)
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The Lymphatic System
Learning Objective
16-8 Differentiate the lymphatic and blood
circulatory systems.
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The Lymphatic System
• 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
© 2016 Pearson Education, Inc.
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
© 2016 Pearson Education, Inc.
Host Defenses: Overview
PLAY
© 2016 Pearson Education, Inc.
Animation: Host Defenses: Overview
Check Your Understanding
 Compare the structures and functions of
monocytes and neutrophils.
16-6
 Define differential white blood cell count.
16-7
 What is the function of lymph nodes?
16-8
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Phagocytes
Learning Objectives
16-9 Define phagocyte and phagocytosis.
16-10 Describe the process of phagocytosis, and
include the stages of adherence and
ingestion.
16-11 Identify six mechanisms of avoiding
destruction by phagocytosis.
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Phagocytes
• Phago: from the Greek, meaning eat
• Cyte: from the 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.
Macrophage
Bacterium
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The Mechanism of Phagocytosis
• Chemotaxis
• 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
© 2016 Pearson Education, Inc.
Figure 16.8 The Phases of Phagocytosis.
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Phagocytosis: Overview
PLAY
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Animation: Phagocytosis: Overview
Phagocytosis: Mechanism
PLAY
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Animation: Phagocytosis: Mechanism
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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Virulence Factors: Hiding from Host Defenses
PLAY
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Animation: Virulence Factors: Hiding
from Host Defenses
Virulence Factors: Inactivating Host Defenses
PLAY
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Animation: Virulence Factors: Inactivating
Host Defenses
Phagocytosis: Microbes That Evade It
PLAY
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Animation: Phagocytosis: Microbes
That Evade It
Check Your Understanding
 What do fixed and wandering macrophages do?
16-9
 What is the role of TLRs in phagocytosis?
16-10
 How does each of these bacteria avoid
destruction by phagocytes? Streptococcus
pneumoniae, Staphylococcus aureus, Listeria
monocytogenes, Mycobacterium tuberculosis,
Rickettsia
16-11
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Inflammation
Learning Objectives
16-12 List the stages of inflammation.
16-13 Describe the roles of vasodilation, kinins,
prostaglandins, and leukotrienes in
inflammation.
16-14 Describe phagocyte migration.
© 2016 Pearson Education, Inc.
Inflammation
• Four signs and symptoms: redness, swelling
(edema), pain, heat
• Destroys injurious agent or limits its effects on the
body
• Repairs and replaces tissue damaged by the
injurious agent
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Inflammation
• Inflammation activates acute-phase proteins by
the liver that cause vasodilation and increased
permeability of blood vessels
•
•
•
•
•
Histamine
Kinins
Prostaglandins
Leukotrienes
Cytokines
© 2016 Pearson Education, Inc.
Figure 16.9a-b The process of inflammation.
Tissue damage
Bacteria
Epidermis
Blood
vessel
Dermis
Nerve
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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Inflammation: Overview
PLAY
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Animation: Inflammation: Overview
Inflammation: Steps
PLAY
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Animation: Inflammation: Steps
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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Check Your Understanding
 What purposes does inflammation serve?
16-12
 What causes the redness, swelling, and pain
associated with inflammation?
16-13
 What is margination?
16-14
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Fever
Learning Objective
16-15 Describe the cause and effects of fever.
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Fever
• Abnormally high body temperature
• Hypothalamus is normally set at 37°C
• 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
© 2016 Pearson Education, Inc.
Check Your Understanding
 Why does a chill indicate that a fever is about to
occur?
16-15
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Antimicrobial Substances
Learning Objectives
16-16 List the major components of the complement
system.
16-17 Describe three pathways of activating
complement.
16-18 Describe three consequences of complement
activation.
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Antimicrobial Substances
Learning Objectives
16-19 Define interferons.
16-20 Compare and contrast the actions of IFN-α
and IFN-β with IFN-.
16-21 Describe the role of iron-binding proteins in
innate immunity.
16-22 Describe the role of antimicrobial peptides in
innate immunity.
© 2016 Pearson Education, Inc.
The Complement System
• Serum proteins produced by the liver that assist the
immune system in destroying microbes
• Act in a cascade in a process called complement
activation
• Proteins are designated with uppercase C and
numbered in order of discovery
• Activated fragments are indicated with lowercase a and b
© 2016 Pearson Education, Inc.
Complement: Overview
PLAY
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Animation: Complement: Overview
Complement: Activation
PLAY
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Animation: Complement: Activation
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
© 2016 Pearson Education, Inc.
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
© 2016 Pearson Education, Inc.
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
© 2016 Pearson Education, Inc.
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
© 2016 Pearson Education, Inc.
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
© 2016 Pearson Education, Inc.
Outcomes of Complement Activation
• Cytolysis
• Activated complement proteins create a membrane
attack complex (MAC)
• Opsonization
• 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.
© 2016 Pearson Education, Inc.
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
C5a
C3a
receptor
C9
Channel
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.
© 2016 Pearson Education, Inc.
Figure 16.13 Inflammation stimulated by complement.
Mast cell
C5a receptor
C5a
Phagocytes
Histamine
Neutrophil
Histaminecontaining
granule
C5a
Histaminereleasing
mast cell
© 2016 Pearson Education, Inc.
C3a
C3a receptor
Macrophage
Complement: Results
PLAY
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Animation: Complement: Results
Outcomes of Complement Activation
• Regulation of complement
• Regulatory proteins readily break down complement
proteins, minimizing host cell destruction
• Complement and disease
• Lack of complement proteins causes susceptibility to
infections
• Evading the complement system
• Capsules prevent complement activation
© 2016 Pearson Education, Inc.
Check Your Understanding
 What is complement?
16-16
 List the steps of complement activation via
the classical, alternative, and lectin pathways.
16-17
 Summarize outcomes of complement activation.
16-18
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Interferons
• Cytokines produced by cells; have antiviral activity
• IFN-α and IFN-β: produced by cells in response to
viral infections; cause neighboring cells to produce
antiviral proteins (AVPs) that inhibit viral
replication
• IFN-: causes neutrophils and macrophages
to kill 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: found in blood and tissue fluids
• Lactoferrin: found in milk, saliva, and mucus
• Ferritin: found in the liver, spleen, and red bone
marrow
• Hemoglobin: located in red blood cells
• Bacteria produce siderophores to compete with
iron-binding proteins
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Antimicrobial Peptides
• 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
© 2016 Pearson Education, Inc.
Check Your Understanding
 What is interferon?
16-19
 Why do IFN-α and IFN-β share the same receptor
on target cells, yet IFN- has a different receptor?
16-20
 What is the role of siderophores in infection?
16-21
 Why are scientists interested in AMPs?
16-22
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