The document summarizes the host defenses against pathogens. It describes three lines of defense: physical barriers that block invasion, protective cells and fluids that cause inflammation and phagocytosis, and acquired immunity through antibodies and memory cells. The immune system relies on barriers like skin and mucous membranes, as well as chemicals, cells, and organs like the spleen, lymph nodes, and bone marrow to recognize and destroy foreign substances while leaving self cells unharmed.

1. Chapter 14
An Introduction to
Host Defenses
Innate Immunities
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or
display.

2. *
Defense Mechanisms of the Host
• Host Defenses
– Innate, natural defenses: present at birth, provide
nonspecific resistance to infection
– Adaptive immunities: specific, must be acquired

3. *
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

4. Sebaceous
glands (fatty
acids)
Tears
(lysozyme)
Mucus
Saliva
(lysozyme,
lactoferrin,
peroxidase)
Commensals
Intact
skin
Wax
Low pH
Cilia
Sweat
Defecation
Urination
Paneth
cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Stomach acid
Mucus
Intestinal enzymes
Mucus
Physical or Anatomical Barriers: First
Line of Defense
Skin and mucous membranes of
respiratory, urogenital, eyes,
and digestive tracts
– Outermost layer of skin is
composed of epithelial cells
compacted, cemented
together, and impregnated
with keratin; few pathogens
can penetrate if intact
– Flushing effect of sweat
glands
– Blinking and tear production
– Stomach acid
*

5. *
Physical or Anatomical Barriers:
First Line of Defense
– Mucous coat impedes attachment and entry of bacteria
– Nasal hair traps larger particles
Pharynx
Epiglotti
s
Nasal cavity
Right
lung
(a)
(b) Left
lung
Nostri
l
Oral cavity
Larynx
Bronchu
s
Bronchiole
s
Trachea
Cilia
Microvill
i
Copyright © The McGraw-Hill Companies, Inc. Permission required for
reproduction or display.
© Louisa Howard/Dartmouth College

6. *

7. *
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

8. *
Genetic Defenses
• Some hosts are genetically immune to the
diseases of other hosts
• Some pathogens have great specificity
• Some genetic differences exist in
susceptibility

9. Contact
with self cells
Contact with
a foreign cell
No
reaction
WBC Normal
Self
molecule
s
WBC
PAMPs*
on
microbe
Pathogen
recognition receptor (PRR)
Destructio
n
Surveillance
Body
compartments are
screened by
circulating WBCs.
Detection and
recognition
of foreign cell or
virus
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
*
Structure and Function of the
Organs of Defense and Immunity
• The study of the body’s
second and third lines of
defense is called
immunology
• Functions of a healthy
functioning immune
system:
1. Surveillance of the body
2. Recognition of foreign
material
3. Destruction of entities
deemed to be foreign

10. *
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

11. *
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

12. ECF
ECF
ECF
ECF
Reticul
ar
fibers
(a) (b)
Lymphatic
capillaries
White blood
cells Tissue
cells
Blood
capillary
(extracellular
fluid)
RE
system
Blood
Lymphatics
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
*
Body Compartments that
Participate in the Immune System
• The reticuloendothelial system
• The extracellular fluid
• The bloodstream
• The lymphatic system

13. *
Reticuloendothelial System (RES)
• Network of connective tissue
fibers that interconnects
other cells and meshes with
the connective tissue
network surrounding organs
• Inhabited by phagocytic cells
– mononuclear phagocyte
system – macrophages
ready to attack and ingest
microbes that passed the
first line of defense
Macrophag
e
Dendriti
c
cell
Neutrophi
l
Tissue
cell
(a)
(b)
Reticular
fibres
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

14. *
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

15. *
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
Plasma
Red
blood
cells
Buffy
coat
Serum
Clo
t
(a) Unclotted Whole Blood (b) Clotted Whole Blood
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

16. *
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

17. *
Blood Cells
Erythroblast Megakaryoblast Monoblast Lymphoblasts
Megakaryocyte
Myeloblast
Red blood cells
Carry O2
and CO2
Platelets
Involved in
blood clotting
and
inflammation
Neutrophils
Phagocytes;
active engulfers
and killers
of bacteria
Basophils
Function in
inflammatory
events and
allergies
Eosinophils
Active in worm
and fungal infections,
allergy, and
inflammation
Monocytes
Blood phagocytes that rapidly
leave the circuation; mature
intomacrophages and dendritic
cells
Lymhocytes
Primary cells involved in
specific immune reactions to
foreign matter
T cells
Perform a number of specific
immune responses such as
assisting B cells and cell-
mediated immunity
B cells
Differentiate into plasma cells and
form antibodies (humoral
immunity)
Natural Killer (NK) cells
Related to T cells but
displaying no specificity;
active against cancerous and
virally infected cells
Macrophages
Largest phagocytes; ingest
and kill foreign cells;
required for certain specific
immune reactions
Dendritic cells
Relatives of macrophages; reside
throughout the tissues and
reticuloendothelial system;
involved in early immune reactions
with foreign matter
Mast cells
Tissue cells similar to
basophills that trigger local
inflammatory reactions and
allergic symptoms
Neutrophil Basophil Eosinophil Monocyte Lymphocyte
Myeloid stem cell
makes all blood cells
except lymphocytes
Hematopoietic
Stem cell
(in bone marrow)
Lymphoid
stem cell
White blood cells (leukocytes)
categorized by
staining characteristics
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
© Harold J. Benson
© Harold J. Benson
© Harold J. Benson © Harold J. Benson © Harold J. Benson

18. *
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

19. *
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

20. *
Leukocytes

21. *
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

22. *
Lymphatic System
1. Provides an auxiliary
route for return of
extracellular fluid to
the circulatory system
2. Acts as a drain-off
system for the
inflammatory response
3. Renders surveillance,
recognition, and
protection against
foreign material
Right lymphatic
duct
Axillary lymph
nodes
Lymphatic
s
of breast
Bone marrow
Right subclavian
vein
Lymphatic
vessels
Tonsils (MALT)
Thymus
Axillary lymph node
MALT (mucosal-associated
lymphoid tissue) in breast
Spleen
GALT (Peyer’s patches
in small intestine)
Inguinal lymph node
(b)
(a)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

23. *
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

24. Lymphatic
trunks
Lymph
nodes
Lymph
flow
Collecting
ducts
Capillaries
Capillaries
Subclavian vein
Superior
vena cava
Lymphatic
capillaries
Lymphatic
system
Cardiovascular
system
Lymphati
c
capillaries
Collecting
vessels
Bloo
d
flow
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
*
Lymphatic Vessels
• Lymphatic capillaries
permeate all parts of the
body except the CNS, bone,
placenta, and thymus
• Thin walls easily permeated
by extracellular fluid which
is then moved through
contraction of skeletal
muscles
• Functions to return lymph to
circulation; flow is
one-direction – toward the
heart – eventually returning
to blood stream

25. Medulla
Veins that feed into heart
Blood
circulatio
n
Efferent
lymphati
c
duct
Lymphatic
duct
Lymphatic
duct
Lymphatic
duct
Capillary
bed
Lymph capillary
Tissue cells
Venule
Arteriole
Afferent
Lymphati
c
ducts
Parafollicle
region
Cortica
l
follicles
a
b
d
e
c
(b) The ducts carry lymph into a circuit of
larger ducts that ultimately flow into
clusters of filtering organs, the lymph
nodes.
(c) A section through a lymph node reveals
the afferent ducts draining lymph into
sinuses that house several types of white
blood cells. Here, foreign material is filtered
out and processed by lymphocytes,
macrophages, and dendritic cells.
(d) and (e) Lymph continues to trickle from
the lymph nodes via efferent ducts into a
system of larger drainage vessels, which
ultimately connect with large veins near
the
heart. In this way, cells and products of
immunity continually enter the regular
Circulation.
Lymph
duct
Section
of lymph
node
Lymph
node
(a) The finest level of lymphatic circulation
begins with blind capillaries (green) that
pick up foreign matter from the
surrounding tissues and transport it in
lymph away from the extremities via a
system of small ducts.
At
cellular
level
of
anatomy
At
regional
level
of
anatomy
Major
transport
vessels
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
*
Circulation in the Lymphatic Vessels
and Lymph Nodes

26. *
Lymphoid Organs and Tissues
• Classified as primary and
secondary
• Primary lymphoid organs
– sites of lymphocytic origin
and maturation – thymus
and bone marrow
• Secondary lymphoid
organs and tissues –
circulatory-based locations
such as spleen and lymph
nodes; collections of cells
distributed throughout body
tissues – skin and mucous
membranes – SALT, GALT,
MALT
Corte
x
Medull
a
Thymus
gland
Blood
vessels
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

27. *
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

28. *
Concept Check:
T cells mature in the
A. Lymph Nodes
B. Spleen
C. Thymus
D. GALT

29. *
Actions of the Second Line of
Defense
• Recognition
• Inflammation
• Phagocytosis
• Interferon
• Complement

30. *
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
Injury Rubor,
calor
Tumor Dolor, Loss
of function
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

31. *
The Major Events in Inflammation
(a) Injury/Immediate Reactions (b) Vascular
Reactions
(c) Edema and Pus
Formation
(d) Resolution/Scar
Formation
Bacteria in
wound
Mast cells release
chemical
mediators
Vasoconstricti
on
Clo
t
Bacteri
a
Neutrop
hil
Vasodilatio
n
Sca
b
Neutrophi
ls
Fibrous
exudate
Sca
r
Lymphocyt
es
Macropha
ge
Pu
s
Rubor/calor
of
inflammation
Edema
(tumor)
and dolor
Repaired or
damaged
tissue
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

32. *
The Chemical Mediators of the
Inflammatory Response
Increased permeability
of capillaries and small veins
Stimulation
of nerves;
pain
Vasoconstriction
L
y
mphocyte
s
Platelet
s
Macrophage
s
Neutrophil
s
Chemotactic
Actions
Vasoactive
Actions
Edem
a
Acut
e
Chroni
c
Vasodilatio
n
Mediators with Both Vasoactive
and
Chemotactic Effects
Complement
components
Cytokines such as
interferon and
interleukin
Some products of arachidonic
acid
metabolism
Platelet
activators
Chemical Mediators
with Vasoactive
Effects
Histamin
e
Serotoni
n
Bradykini
n
Prostaglandin
s
Substances with
Chemotactic
Effects
Endotoxi
n
Platelet activating
factor
Leukotrien
e
Cells migrate to site
of damage
Major
phagocytes
Major
phagocytes
and support for
immune
reactions
Respond
Specifically
to
pathogens
Release
mediator
s
Productio
n
of
Mediators
Mast cell chemotactic
factors
Bacterial peptides,
PAMPs
Initiating Event
Trauma, infection,
necrosis, foreign
particle,
neoplasm
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

33. *
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
Chemotaxi
s
Diapedesis
Marginatio
n
Blood
vessel
Endothelial cell
Neutrophil
s
Tissue space
Chemotactic
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

34. *
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

35. *
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 (??)

36. *
Phagocytes and Phagocytosis
Neutrophils – general-purpose;
react early to bacteria and
other foreign materials, and
to damaged tissue
Eosinophils – attracted to sites
of parasitic infections and
antigen-antibody reactions
Macrophages – derived from
monocytes; scavenge and
process foreign substances
to prepare them for
reactions with B and T
lymphocytes
Macrophag
e
Dendritic
cells
Tissue
Bloo
d
Marro
w
Stem cell Promoncyt
e
Monocyte
s
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

37. *
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
Macrophage
Toll-like receptor
Nucleus
Foreign molecule
Cytokines
Interleukins
Inflammatory mediators
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

38. *
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

39. *
Phagocytosis
Lysosomes
Chemotaxis by
phagocyte
Adhesion of
bacteria
Engulfment into
phagocytic
vacuole
Phagosome
Phagolysosome
formation
Killing and destruction of
bacterial cells
Nucleu
s
Rough
endoplasmic
reticulum
Golgi
apparatus
Receptor on host
cell
Bacterial cells
PAMPs
Enzymes
Lysozyme
Dnase Rnase
Proteases
Peroxidase
Release of
residual debris
Reactive oxygen
products
Superoxide (O2
−
•)
Hydrogen peroxide (H2
O2
)
Singlet oxygen (1
O2
)
Hydroxyl ion (OH—
)
Hypochlorite ion (HClO—
)
1
2
3
4
5
6
7
© Dr. Brinkmann/Max Planck Institute for Infection Biology
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

40. *
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
Degrades virus
nucleic acid
Blocks virus
replication
Virus
release
Assembly
of viruses
Viral
nucleic
acid
Virus
infectio
n
Infecte
d
cell
Nearby
cell
Attachment of IFN
to special receptor
Synthesis of antiviral proteins
Signals
activation of genes
Synthesis
of IFN
IFN
gene
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

41. *
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

42. *
4 Stages in the Complement Cascade
1. Initiation
2. Amplification
and cascade
Other molecules given off:
C3a
, C5a
which are peptide
mediators of inflammation,
phagocyte recruitment
(b)
(a)
Cascade and Amplification. C5 factor
is acted on by C3b
, which converts it to
C5b
. C5b
becomes bound to the
membrane and serves as the starting
molecule for the chain of events that
assemble the complex in (c) and (d).
C3
Convertase
Classical Pathway MB-Lectin Pathway Alternative Pathway
Complement-fixing
antibodies (discussed in
chapter 15) rapid, specific
Mannose-binding lectin (MBL)
binds mannose on pathogen
surfaces. Nonspecific for
bacteria and viruses
C1q, C1r, C1s
C4
C2
C3
MBL, MASP-1, MASP-2
C4
C2
C3
C3 convertase enzyme converts
C3 molecule into an activator—C3b
Molecules on surfaces of
bacteria, fungi, viruses, and
parasites.
Nonspecific
Factor B
Factor D
C3
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
C3
b
C5b

43. *
4 Stages in the Complement Cascade
3. Polymerization
4. Membrane
attack
Complete
d
MAC
Lysis
C5b
6789 Membrane-
attack complex,
lysis of certain
pathogens
and cells
Terminal
complement
components
C5b
C6
C7
C8
C9
(c) Polymerization. C5b
is a reactive site for
the final assembly of an attack complex.
In series, C6, C7, and C8 aggregate with
C5b
and become integrated into the
membrane. They form a substrate upon
which the final component, C9, can bind.
Up to 15 of these C9 units ring the
central core of the final membrane attack
complex (MAC).
(d) Membrane Attack. Insertion of MACs
produces hundreds of tiny holes in the
cell membrane. This can cause lysis
and death of eukaryotic cells and
many
gram-negative bacteria.
C8
C9
C7
C6
C5b
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

44. *
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

45. *
Overview of the Major Host Defenses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
HOST
DEFENCES
See
Chapter
15
The second line of defense is a
cellular and chemical system that
comes immediately into play if
infectious agents make it past the
surface defenses. Examples include
phagocytes that destroy foreign
matter, and inflammation which holds
infections in check.
The third line of defense includes
specific host defenses that must be
developed uniquely for each microbe
through the action of specialized
white blood cells. This form of
immunity is marked by its activity
toward specific pathogens and
development of memory.
Innate,
nonspecific
Acquired,
specific
B and T lymphocytes,
antibodies, cytotoxicity
Second
line
of defense
First line
pf
defence
Physical
barriers
Chemical
barriers
Genetic
barriers
Inflammatory
response
Interferons Phagocytosis Complement
The first line of defense is a
surface protection composed of
anatomical and physiological
barriers that keep microbes
from penetrating sterile body
compartments.
Third line
of
defense