Chapter 14

An Introduction to
Host Defenses
Innate Immunities

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display.
Defense Mechanisms of the Host
• Host Defenses
– Innate, natural defenses: present at birth, provide
nonspecific resistance to infection
– Adaptive immunities: specific, must be acquired

*
Defense Mechanisms of the Host
• To protect the body against pathogens, the immune
system relies on a multilevel network of physical
barriers, immunologically active cells, and a variety of
chemicals
– First line of defense – any barrier that blocks
invasion at the portal of entry – nonspecific
– Second line of defense – protective cells and
fluids; inflammation and phagocytosis – nonspecific
– Third line of defense – acquired with exposure to
foreign substance; produces protective antibodies
and creates memory cells – specific

*
 Physical or Anatomical Barriers: First
Line of Defense Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Sebaceous
glands (fatty
acids)

Skin and mucous membranes of Tears

(lysozyme)

respiratory, urogenital, eyes, Mucus

Saliva
Wax

and digestive tracts (lysozyme,

lactoferrin,
peroxidase)

– Outermost layer of skin is Intact

skin
Cilia Low pH

composed of epithelial cells Mucus

compacted, cemented Sweat

together, and impregnated

with keratin; few pathogens Stomach acid

can penetrate if intact Commensals

– Flushing effect of sweat Intestinal enzymes

Mucus
Paneth
cells
glands
– Blinking and tear production
– Stomach acid
Defecation
*
Urination
 Physical or Anatomical Barriers:
First Line of Defense
– Mucous coat impedes attachment and entry of bacteria
– Nasal hair traps larger particles
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reproduction or display.
Nasal cavity

Nostri
l
Oral cavity Pharynx
Epiglotti
Larynx s

Trachea

Bronchu
s
Bronchiole
s

© Louisa Howard/Dartmouth College

*
(b) Microvill Cilia (a) Right Left
i lung lung
*
Nonspecific Chemical Defenses
• Sebaceous secretions
• Lysozyme, an enzyme that hydrolyzes the cell
wall of bacteria, in tears
• High lactic acid and electrolyte concentration in
sweat
• Skin’s acidic pH
• Hydrochloric acid in stomach
• Digestive juices and bile of intestines
• Semen contains an antimicrobial chemical
• Vagina has acidic pH
*
 Genetic Defenses
• Some hosts are genetically immune to the
diseases of other hosts
• Some pathogens have great specificity
• Some genetic differences exist in
susceptibility

*
 Structure and Function of the
Organs of Defense and Immunity
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Contact

• The study of the body’s with self cells

second and third lines of

No
defense is called reaction

immunology WBC Normal

Self
molecule
• Functions of a healthy s
Contact with
functioning immune a foreign cell

system:
1. Surveillance of the body PAMPs*

2. Recognition of foreign WBC

on
microbe

material Pathogen
recognition receptor (PRR)

3. Destruction of entities Surveillance Detection and

recognition
Destructio
n
deemed to be foreign compartments
Body
are
of foreign cell or
virus
screened by
circulating WBCs.
*
 Immune System
• Large, complex, and diffuse network of cells
and fluids that penetrate into every organ
and tissue

• Four major subdivisions of immune system:

1. Reticuloendothelial system (RES)
2. Extracellular fluid (ECF)
3. Bloodstream
4. Lymphatic system

*
 Immune System Definitions
• White blood cells (leukocytes) – innate
capacity to recognize and differentiate any
foreign material
• Nonself – foreign material
• Self – normal cells of the body
• Pathogen-associated patterns (PAMPs) –
molecules shared by microorganisms
• Pathogen recognition receptors (PRRs) –
receptors on WBCs for PAMPs

*
 Body Compartments that
Participate in the Immune System
• The reticuloendothelial system • The bloodstream
• The extracellular fluid • The lymphatic system
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White blood Lymphatic

cells capillaries Tissue
cells
Blood
capillary Blood
ECF

ECF

ECF

RE Lymphatics
Reticul system
ar
fibers ECF
(extracellular
fluid) *
(a) (b)
 Reticuloendothelial System (RES)
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• Network of connective tissue
fibers that interconnects Macrophag
other cells and meshes with Dendriti e Neutrophi
l
the connective tissue c
cell
network surrounding organs

• Inhabited by phagocytic cells

– mononuclear phagocyte
system – macrophages Tissue Reticular
ready to attack and ingest (a)
cell fibres

microbes that passed the

first line of defense (b)

*
 Concept Check:
Which of the following is NOT an example of a first line
defense?

A. White blood cells

B. Lysozyme
C. Hydrochloric acid in the stomach
D. The sneeze reflex
E. Cilia in the respiratory tract
*
 Origin, Composition, and
Functions of the Blood
• Whole blood consists of plasma and formed elements
(blood cells)
– Serum is the liquid portion of the blood after a clot has
formed – minus clotting factors
• Plasma – 92% water, metabolic proteins, globulins,
clotting factors, hormones, and all other chemicals and
gases to support normal physiological functions
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Plasma Serum
Buffy
coat Red Clo
blood t
*
cells
(a) Unclotted Whole Blood (b) Clotted Whole Blood
 A Survey of Blood Cells
• Hemopoiesis – production of blood cells
(hemo – blood, poiesis – to make)
• Stem cells – undifferentiated cells, precursor
of new blood cells
• Leukocytes – White blood cells
– Granulocytes: lobed nucleus
– Agranulocytes: unlobed, rounded nucleus

*
 Blood Cells
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Myeloid stem cell Hematopoietic

makes all blood cells Stem cell
except lymphocytes (in bone marrow)
Lymphoid
stem cell

Erythroblast Megakaryoblast Monoblast Lymphoblasts

White blood cells (leukocytes)

Myeloblast
categorized by
Megakaryocyte staining characteristics

Red blood cells Platelets Neutrophils Basophils Eosinophils Monocytes Lymhocytes

Carry O2 and CO2 Involved in Phagocytes; Function in Active in worm Blood phagocytes that rapidly Primary cells involved in
blood clotting active engulfers inflammatory and fungal infections,leave the circuation; mature specific immune reactions to
and and killers events and allergy, and intomacrophages and dendritic foreign matter
inflammation of bacteria allergies inflammation cells
T cells
Perform a number of specific
immune responses such as
assisting B cells and cell-
mediated immunity

B cells
Macrophages
Differentiate into plasma cells and
Largest phagocytes; ingest
form antibodies (humoral
and kill foreign cells;
immunity)
required for certain specific
immune reactions
Mast cells
Tissue cells similar to
basophills that trigger local Dendritic cells
inflammatory reactions and Relatives of macrophages; reside
allergic symptoms throughout the tissues and
Natural Killer (NK) cells
reticuloendothelial system;
Related to T cells but
involved in early immune reactions
displaying no specificity;
with foreign matter
active against cancerous and
virally infected cells

*
© Harold J. Benson © Harold J. Benson © Harold J. Benson © Harold J. Benson © Harold J. Benson
Neutrophil Basophil Eosinophil Monocyte Lymphocyte
 Granulocytes
• Neutrophils – 55-90% - lobed nuclei with
lavender granules; phagocytes

• Eosinophils – 1-3% - orange granules and

bilobed nucleus; destroy eukaryotic pathogens

• Basophils – 0.5% - constricted nuclei, dark blue

granules; release potent chemical mediators
– Mast cells: nonmotile elements bound to
connective tissue
*
 Agranulocytes
• Lymphocytes – 20-35%, specific immune
response
– B (humoral immunity): activated B cells produce
antibodies
– T cells (cell-mediated immunity): activated T cells
modulate immune functions and kill foreign cells

• Monocytes, macrophages – 3-7% - largest of

WBCs, kidney-shaped nucleus; phagocytic
– Macrophages: final differentiation of monocytes
– Dendritic cells: trap pathogens and participate in
immune reactions

*
Leukocytes

*
Erythrocytes and Platelet Lines
• Erythrocytes: develop from bone marrow
stem cells, lose nucleus, simple biconcave
sacs of hemoglobin

• Platelets: formed elements in circulating

blood that are not whole cells

*
 Lymphatic System
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1. Provides an auxiliary Right lymphatic

route for return of duct

Right subclavian
vein
extracellular fluid to Axillary lymph
nodes
Tonsils (MALT)

the circulatory system Thymus

Axillary lymph node
Lymphatic
s MALT (mucosal-associated
of breast lymphoid tissue) in breast
2. Acts as a drain-off Spleen

system for the GALT (Peyer’s patches

inflammatory response (b) in small intestine)

Inguinal lymph node

3. Renders surveillance, Bone marrow

recognition, and Lymphatic

protection against vessels

foreign material
(a)

*
 Lymphatic Fluid
• Lymph is a plasma-like liquid carried by
lymphatic circulation

• Formed when blood components move out of

blood vessels into extracellular spaces

• Made up of water, dissolved salts, 2-5%

proteins

• Transports white blood cells, fats, cellular

debris, and infectious agents

*
 Lymphatic Vessels
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Lymphatic Cardiovascular
system system
• Lymphatic capillaries Lymphati
c Capillaries
permeate all parts of the capillaries
Lymph
body except the CNS, bone, nodes
Lymphatic
placenta, and thymus trunks
Collecting
Subclavian vein

• Thin walls easily permeated ducts

by extracellular fluid which Collecting Superior

vena cava
vessels
is then moved through
contraction of skeletal
muscles Bloo
d
• Functions to return lymph to flow

circulation; flow is Lymph

flow
one-direction – toward the
heart – eventually returning Capillaries

to blood stream Lymphatic

*
capillaries
Circulation in the Lymphatic Vessels
and Lymph Nodes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Lymph capillary

Tissue cells Capillary

(a) The finest level of lymphatic circulation bed
begins with blind capillaries (green) that
pick up foreign matter from the a
surrounding tissues and transport it in

At cellular level
lymph away from the extremities via a

of anatomy
system of small ducts.

(b) The ducts carry lymph into a circuit of Venule

larger ducts that ultimately flow into b
Lymph
clusters of filtering organs, the lymph Arteriole
duct
nodes.

(c) A section through a lymph node reveals Afferent

At regional level
the afferent ducts draining lymph into c

of anatomy
Lymphati
sinuses that house several types of white Section c
blood cells. Here, foreign material is filtered of lymph ducts
Parafollicle
out and processed by lymphocytes, node region
macrophages, and dendritic cells. Medulla Cortica
Lymph Efferent l
node lymphati follicles
c
(d) and (e) Lymph continues to trickle from duct
t ic
the lymph nodes via efferent ducts into a pha
Lym t

transport
vessels
Major
system of larger drainage vessels, which d duc
ultimately connect with large veins near
the Lymphatic
Lymphatic duct
heart. In this way, cells and products of e duct
immunity continually enter the regular
Blood
*
Circulation. circulatio Veins that feed into heart
n
 Lymphoid Organs and Tissues
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• Classified as primary and

secondary
• Primary lymphoid organs
– sites of lymphocytic origin
and maturation – thymus
and bone marrow
• Secondary lymphoid
Thymus
organs and tissues – gland
circulatory-based locations
such as spleen and lymph Blood
nodes; collections of cells vessels

distributed throughout body

tissues – skin and mucous
Corte Medull
membranes – SALT, GALT, x a
MALT *
 Lymphoid Organs
• Thymus – high rate of growth and activity until puberty,
then begins to shrink; site of T-cell maturation

• Lymph nodes – small, encapsulated, bean-shaped

organs stationed along lymphatic channels and large
blood vessels of the thoracic and abdominal cavities

• Spleen – structurally similar to lymph node; filters

circulating blood to remove worn out RBCs and
pathogens

• Miscellaneous – GALT, Peyer’s patch

*
 Concept Check:
T cells mature in the

A. Lymph Nodes
B. Spleen
C. Thymus
D. GALT

*
Actions of the Second Line of
Defense
• Recognition
• Inflammation
• Phagocytosis
• Interferon
• Complement

*
 Inflammatory Response
Classic signs and symptoms characterized by:
• Redness – increased circulation and vasodilation in
injured tissues in response to chemical mediators
• Warmth – heat given off by the increased blood flow
• Swelling – increased fluid escaping into the tissue as
blood vessels dilate – edema; WBC’s, microbes, debris,
and fluid collect to form pus; prevents spread of infection
• Pain – stimulation of nerve endings
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*
Injury Rubor, Tumor Dolor, Loss
calor of function
The Major Events in Inflammation
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Clo
tBacteri
Bacteria in a
Neutrop
wound
Mast cells release hil
chemical
mediators
Vasoconstricti
on Vasodilatio
n

(a) Injury/Immediate Reactions (b) Vascular

Reactions

Sca
b
Neutrophi Sca
ls r
Pu Lymphocyt
s es
Fibrous Macropha
exudate ge

(c) Edema and Pus (d) Resolution/Scar

Formation Formation
Rubor/calor Edema Repaired or
*
of (tumor) damaged
inflammation and dolor tissue
The Chemical Mediators of the
Inflammatory Response
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Vasoactive Initiating Event Chemotactic

Actions Trauma, infection, Actions
necrosis, foreign Cells migrate to site
particle, of damage
Vasodilatio neoplasm
n
Increased permeability Neutrophil Major
of capillaries and small veins s phagocytes

t Platelet Release
Acu
e s mediator
s
Productio
n
Stimulation of Macrophage Major
Mediators Ch s phagocytes
of nerves; c ro
n i and support for
pain
immune
reactions
Vasoconstriction
L mphocyte Respond
ys Specifically
to
Edem
pathogens
a
Chemical Mediators Mediators with Both Vasoactive Substances with
with Vasoactive and Chemotactic
Effects Chemotactic Effects Effects
Histamin Complement Endotoxi
e components n
Serotoni Cytokines such as Platelet activating
n interferon and factor
Bradykini interleukin Leukotrien
n Some products of arachidonic e
Prostaglandin acid Mast cell chemotactic *
s metabolism factors
Platelet Bacterial peptides,
activators PAMPs
Unique Characteristics of Leukocytes

• Diapedesis – migration of cells out of blood vessels

into the tissues
• Chemotaxis – migration in response to specific
chemicals at the site of injury or infection
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Endothelial cell
Blood
vessel

Marginatio
n Diapedesis

Neutrophil
s

Tissue space *
Chemotaxi
s
Chemotactic
 Fever
• Initiated by circulating pyrogens which reset the
hypothalamus to increase body temperature;
signals muscles to increase heat production and
vasoconstriction
– Exogenous pyrogens – products of infectious agents
– Endogenous pyrogens – liberated by monocytes,
neutrophils, and macrophages during phagocytosis;
interleukin-1 (IL-1) and tumor necrosis factor (TNF)
• Benefits of fever:
– Inhibits multiplication of temperature-sensitive
microorganisms
– Impedes nutrition of bacteria by reducing the available
iron
– Increases metabolism and stimulates immune
reactions and protective physiological processes
*
 Phagocytosis
General activities of phagocytes:
1. To survey tissue compartments and
discover microbes, particulate matter, and
dead or injured cells
2. To ingest and eliminate these materials
3. To extract immunogenic information from
foreign matter (??)

*
 Phagocytes and Phagocytosis
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Neutrophils – general-purpose; Marro

react early to bacteria and w

other foreign materials, and Stem cell Promoncyt

e

to damaged tissue
Eosinophils – attracted to sites
of parasitic infections and Bloo Monocyte
antigen-antibody reactions d s

Macrophages – derived from

monocytes; scavenge and
process foreign substances
to prepare them for
reactions with B and T Tissue

lymphocytes
Macrophag Dendritic
e cells
*
 Recognition of Foreign Cells
• Protein receptors within cell membrane of macrophages,
called Toll-like receptors
• Detect foreign molecules and signal the macrophage to
produce chemicals to stimulate an immune response
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Toll-like receptor Foreign molecule

Nucleus

Macrophage
Cytokines
Interleukins
*
Inflammatory mediators
 Mechanisms of Phagocytic
Recognition, Engulfment, and Killing
• Chemotaxis and ingestion: phagocytes
migrate and recognize PAMPs
– Phagosome
• Phagolysosome: lysosome fused with
phagosome (death ~30 minutes)
• Destruction and elimination
– Oxygen-dependent system (respiratory burst)
– Liberation of lactic acid, lysozyme, and nitric oxide

*
 Phagocytosis
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1 Chemotaxis by
phagocyte

Bacterial cells

PAMPs 2 Adhesion of
bacteria

Receptor on host
cell

3 Engulfment into
phagocytic Lysosomes
vacuole
Golgi
apparatus
Rough
endoplasmic
reticulum

© Dr. Brinkmann/Max Planck Institute for Infection Biology

4 Phagosome

5 Phagolysosome
formation

Enzymes
Lysozyme
Dnase Rnase
6 Killing and destruction of Proteases Nucleu
bacterial cells Peroxidase s

Reactive oxygen
products
Superoxide (O2−•)
7 Release of Hydrogen peroxide (H2O2)
residual debris Singlet oxygen (1O2)
Hydroxyl ion (OH— )
Hypochlorite ion (HClO— )
*
 Interferon
• Small protein produced by certain WBCs and tissue cells
– Interferon alpha – lymphocytes and macrophages
– Interferon beta – fibroblasts and epithelial cells
– Interferon gamma – T cells
• Produced in response to viruses, RNA, immune products,
and various antigens, they bind to cell surfaces and
induce expression of antiviral proteins and inhibit
expression of cancer genes
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Assembly
Viral Degrades virus
of viruses Blocks virus
Virus nucleic nucleic acid
Virus replication
infectio acid
release
n

Synthesis of antiviral proteins

IFN
gene
Synthesis Attachment of IFN
of IFN to special receptor
Signals
activation of genes

Infecte Nearby
*
d cell
cell
 Complement
• Consists of 26 blood proteins that work in concert to
destroy bacteria and viruses
• Complement proteins are activated by cleavage (cascade
reaction)
• Pathways
– Classical – activated by the presence of antibody
bound to microorganism
– Lectin pathway – nonspecific reaction of a host serum
protein that binds mannan
– Alternative – begins when complement proteins bind to
normal cell wall and surface components of
microorganisms

*
4 Stages in the Complement Cascade
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(a)

1. Initiation Classical Pathway MB-Lectin Pathway

Mannose-binding lectin (MBL)

Alternative Pathway

Molecules on surfaces of
Complement-fixing
antibodies (discussed in binds mannose on pathogen bacteria, fungi, viruses, and
chapter 15) rapid, specific surfaces. Nonspecific for parasites.
bacteria and viruses Nonspecific

C1q, C1r, C1s MBL, MASP-1, MASP-2

Factor B
C4 C4
Factor D
C2 C2
C3
C3 C3

C3 convertase enzyme converts

C3 molecule into an activator—C3b

2. Amplification (b) Cascade and Amplification. C5 factor

C3
Convertase

is acted on by C3b, which converts it to C5b

and cascade C5b. C5b becomes bound to the

membrane and serves as the starting
molecule for the chain of events that
C3
b

assemble the complex in (c) and (d). Other molecules given off:
C3a, C5a which are peptide
mediators of inflammation,
phagocyte recruitment

*
4 Stages in the Complement Cascade
3. Polymerization
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C8

Complete
d
(c) Polymerization. C5b is a reactive site for C7 MAC
the final assembly of an attack complex. C6 Terminal
In series, C6, C7, and C8 aggregate with
C5b complement
C5b and become integrated into the
components
membrane. They form a substrate upon
C5b
which the final component, C9, can bind.
C6
Up to 15 of these C9 units ring the
C7
central core of the final membrane attack
C8

4. Membrane
complex (MAC).
C9
Lysis

C9

attack (d) Membrane Attack. Insertion of MACs

produces hundreds of tiny holes in the
C5b6789 Membrane-
attack complex,
cell membrane. This can cause lysis lysis of certain
and death of eukaryotic cells and pathogens
many and cells
gram-negative bacteria.

*
 Concept Check:
Which of the following defenses is most likely to be active
during a viral infection?

A. Inflammation
B. Fever
C. Interferon
D. Complement

*
 Overview of the Major Host Defenses
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HOST
DEFENCES
See
Chapter
15

Innate, Acquired,
nonspecific specific

First line Second Third line

pf line of
defence of defense defense

Physical Chemical Genetic Inflammatory B and T lymphocytes,

Interferons Phagocytosis Complement
barriers barriers barriers response antibodies, cytotoxicity

The first line of defense is a The second line of defense is a The third line of defense includes
surface protection composed of cellular and chemical system that specific host defenses that must be
anatomical and physiological comes immediately into play if developed uniquely for each microbe
barriers that keep microbes infectious agents make it past the through the action of specialized
from penetrating sterile body surface defenses. Examples include white blood cells. This form of
compartments. phagocytes that destroy foreign immunity is marked by its activity
matter, and inflammation which holds toward specific pathogens and
infections in check. development of memory.