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Chapter 16
Nonspecific Defenses of
the Host
Terminology
• Resistance: ability to ward off disease
through nonspecific and specific defenses
• Susceptibility: lack of resistance to a
disease
• Nonspecific resistance: defenses against any
pathogen regardless of species
• Specific resistance (immunity): resistance to
a specific pathogen based on lymphocytes
and the production of antibodies
Host Defenses
Figure 16.1
Skin and Mucous Membranes
• Mechanical Factors: physical barriers to
entry or processes that remove microbes from
the body’s surface
– Intact skin
structure of intact skin; keratin;
dryness of the skin & periodic shedding of the
epidermis
• epidermis: outer & thinner portion; in direct contact
with the external environment; tightly packed cells;
top layer of epidermal cells is dead and contains
keratin (protective protein)
• dermis: inner & thicker portion composed of
connective tissues
Mechanical factors
– Mucous membranes
inhibit the entrance of
many microorganism, but provide less protection than
the skin; secretion of mucus; ciliary escalator
• an epithelial layer and an underlying connective tissue
layer
• some pathogens can penetrate the mucous membrane if
present in large numbers (via secretion of toxic substances,
prior injury by viral infection, or mucous irritation)
• mucus secreted by goblet cells in the epithelial layer
traps many of the microorganisms (respiratory and
gastrointestinal tracts)
• ciliary escalator: inhaled microbes, dust, and pollutants
trapped in mucus are transported away from the lungs
toward throat
Mechanical factors
– Lacrimal apparatus
protects the eyes;
continuous washing by tears keep microbes from
settling on the surface of the eye
• a group of structures that manufactures and drains tears
– Saliva
dilutes and washes microbes off;
prevents microbial colonization
– Urine
flows out; prevents microbial
colonization
– Vaginal secretions
flows out to prevent
microbial colonization
Skin and Mucous Membranes
• Chemical factors: substances made by the
body that inhibit microbial growth or
destroy them
– Sebum
forms protective film over the
surface of the skin; unsaturated fatty acids
inhibit the growth of certain pathogenic bacteria
and fungi
• oily substance produced by sebaceous glands of the
skin
– Low pH (3-5) of skin
many microbes
prevents growth of
Chemical factors
– Perspiration
washes off microbes from skin
– Lysozyme in perspiration, tears, saliva, and tissue
fluids
breaks down cell walls of gram-positive
bacteria (peptidoglycan) and some gram-negative
cell walls
– Low pH (1.2-3.0) of gastric juice
destroy most
bacteria and bacterial toxins
• exceptions: enteric pathogens that are protected by food
particles; Helicobacter pylori; toxins of Clostridium
botulinum and Staphylococcus aureus
– Transferrins in blood bind iron
– NO (nitric oxide) inhibits ATP production
Skin and Mucous Membranes
• Normal microbiota and nonspecific resistance
– Microbial antagonism: normal microbiota
compete with pathogens for nutrients (competitive
exclusion), by producing substances (e.g.
bacteriocins) that are harmful to the pathogens, and
by altering conditions (e.g. pH and O2 availability)
Phagocytosis
• Second line of defense
• Phago: eat; Cyte: cell
• Ingestion of microbes or particles by a cell,
performed by phagocytes
• Phagocytes: types of white blood cells or
derivatives of white blood cells
Formed elements in blood
• Blood: plasma (fluid portion) and formed
elements (cells and cell fragments)
– Leukocytes: white blood cells
• During infections (esp. bacteria infection) number of
leukocytes may increase or decrease
detected by
differential white blood cell count
– Leukocytosis: increase in total number of white blood
cells e.g. meningitis, infectious mononucleosis,
appendicitis, pneumococcal pneumonia, and gonorrhea
– Leukopenia: decrease in the number of leukocytes e.g.
salmonellosis and brucellosis, and some viral and
rickettsial infections
Differential White Cell Count
• Percentage of each type of white cell in a sample
of 100 white blood cells for a normal condition
Neutrophils
Basophils
Eosinophils
Monocytes
Lymphocytes
60-70%; active in the initial
stages of an infection
0.5-1%; important in inflammation and allergic responses
2-4%; increase during certain
helminthic infections and
hypersensitivity
3-8%; turn into macrophages
when migrate into tissues
20-25%; involved in specific
immunity
Formed elements in blood
• Three principal kinds of leukocytes
– Granulocytes: see presence of large granules in
their cytoplasm under a light microscope after
staining
• neutrophils (polymorphonuclear leukocytes, PMNs,
or poymorphs)
• basophils
• eosinophiles
– Monocytes
not phagocytic until they turn
into macrophages (leaves blood and enter body
tissues)
Formed elements in blood
– Lymphocytes: Involved in specific immunity (T
cells and B cells)
• Phagocytes are activated by cytokines and also
may be activated by components of bacteria
cell wall (e.g. LPS or lipid A)
Actions of phagocytic cells
• Granulocytes (esp. neutrophils) and
monocytes migrate to the infected area when
an infection occurs
– Monocytes develop into macrophages
• swelling of lymph nodes due to maturation and
proliferation of macrophages during an infection
• Fixed macrophages (histiocytes) in lungs, liver, bronchi
• Wandering macrophages roam tissues
• Macrophages also dispose old/worn out blood cells
Actions of phagocytic cells
• Shift in the predominant type of leukocytes
occurs in blood during the course of an
infection
– Granulocytes (esp. neutrophils)
macrophages
• Macrophages predominate in all phases of
viral and fungal infections
Mechanism of phagocytosis
Figure 16.8a
Microbial evasion of phagocytosis
• Inhibit adherence: M
protein, capsules
Streptococcus pyogenes, S. pneumoniae
• Kill phagocytes:
Leukocidins, streptolysin
• Lyse phagocytes:
Membrane attack complex
Staphylococcus aureus, S. pyogenes
Listeria monocytogenes, Trypanosoma
cruzi
• Escape phagosome before it Shigella, Rickettsia
fuses with lysosome
• Prevent phagosomeHIV, Mycobacterium tuberculosis,
lysosome fusion
Plasmodium
• Survive in phagolysosome
Coxiella burnetti
Inflammation
• Local response of the body to injury
triggered by damage to the body tissues
– microbial infection, physical agents, or chemical
agents
• Four sings and symptoms
– redness, pain, heat, and swelling (edema)
– may have 5th sings and symptoms: loss of
function (depends on the site and extent of
damage
• Acute vs.. chronic inflammation
Inflammation
• Functions
– If possible destroy the injurious agent, and
remove it and its by-products from the body
– If not possible to destroy, limit the effects on the
body (confine or wall-off the injurious agent and
its by-products)
– Repair or replace damaged tissues
• Acute-phase proteins activated during
inflammation (e.g. complement, cytokine,
kinins)
Process of Inflammation
Figure 16.9a, b
Inflammation
Figure 16.9c, d
Vasodilation and increased permeability
of blood vessels
• Caused by chemicals released by damaged cells
in response to injury
• 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
Vasodilation and increased permeability
• Vasodilation: increase in diameter of blood
vessels
cause redness (erythema) and heat
by increasing blood flow to the damaged area
• Increased permeability permits defensive
substances and fluid to move into tissue
spaces
cause swelling (edema)
• Nerve damage, irritation by toxins, or the
pressure of edema can cause pain
• Deliver clotting elements to an abscess (focus
of infection)
prevent spread of infection
Phagocyte migration and phagocytosis
• Margination
emigration
phagocytosis
• Certain chemicals attract neutrophils to the
site of injury
– Chemicals produced by invading microbes,
kinins, leukotrienes, chemokines, and component
of complement system
– Chemokines: cytokines that are chemotactic for
phagocytic and T cells; stimulate inflammatory
response and an immune response
Phagocyte migration and phagocytosis
• See shift in leukocyte types at the area of
infection as inflammation continues
– Granulocytes (neutrophils)
monocytes
– Granulocytes tend to die off rapidly
– Macrophages (derived from monocytes) are
several times more phagocytic than granulocytes
• Large enough to phagocytize: destroyed tissues and
debris, destroyed granulocytes, and invading pathogens
• Death of granulocytes and macrophages form
pus
Tissue repair
• Tissues replace dead or damaged cells
– Ability of a tissue to regenerate, or repair itself,
depends on the type of tissue
• skin vs.. cardiac muscle tissue or brain tissue
– New cells produced by stroma (supporting
connective tissue) or parenchyma (functioning
part of the tissue)
• Repair mostly done by parenchyma
near-perfect
reconstruction
• Repair mostly done by stroma
scar tissue
Fever
• Abnormally high body temperature
• Systemic, or overall responses; defense
against disease up to a certain point
• Infection from bacteria (and their toxins, esp.
endotoxins) or virus = most frequent cause of
fever
• Hypothalamus normally set at 37°C
• Gram-negative endotoxins cause phagocytes
to release interleukin 1 (review Fig. 15.6)
Fever
• Hypothalamus releases prostaglandins that reset
the hypothalamus to a high temperature
• Body increases rate of metabolism and shivering
(chill) to raise temperature
• When IL-1 is eliminated, body temperature falls.
(Crisis)
• Release of Alpha tumor necrosis factor (-TNF)
by macrophages and mast cells can also induce
fever
Antimicrobial Substances
•
•
•
•
Nitric oxide (NO)
The complement system
Interferons
The complement system
– A defensive system consisting of over 30 proteins
produced by liver; present in blood and tissues
– Proteins are normally inactive unless split into 2
active fragments
– Proteins activated in a cascade (one reaction
triggers another)
The Complement System
• Opsonization
or immune
adherence:
enhanced
phagocytosis
• Cytolysis:
membrane attack
complex
• Inflammation:
attract phagocytes
Figure 16.10
Effects of Complement Activation
Cytolysis
Figure 16.11
Effects of Complement Activation
Inflammation
Phagocytosis
Figure 16.12
Classical pathway
• First to be discovered
• Initiated by an
antigen-antibody
(Ag-Ab) reaction
• Results in cytolysis,
inflammation, and
opsonization
Figure 16.13
Alternative pathway
• Discovered after
classical pathway
• Activated by contact
between certain
complement proteins
and a pathogen
• Results in
cytolysis,
inflammation, and
opsonization
Figure 16.14
Lectin pathway
• Most recently discovered
• Production of lectins by
liver (due to release of
chemicals from
macrophages) binds to
carbohydrates on
pathogens and function as
opsonin to enhance
phagocytosis
• Result in the same effects
as other pathways
Figure 16.15
Evading the complement system
• Capsules prevent C activation
– Sialic acid discourages opsonization and MAC
formation
• Surface lipid-carbohydrates prevent MAC
formation
– Those not killed by MAC are called serum
resistant
many gram-negative bacteria (cause
systemic infections)
• Enzymatic digestion of C5a (chemotactic
factor) by gram-positive cocci
Interferons (IFNs)
• A class of similar antiviral proteins
produced by certain animal cells after viral
stimulation/infection
interfere with vial
multiplication
• Host-cell-specific but not virus-specific
• Produced by fibroblasts in connective tissue
and by lymphocytes and other leukocytes
• Quite stable at low pH and are fairly
resistant to heat
Interferons
• Alpha interferon and beta interferon are
produced by virus-infected host cells to affect
uninfected neighboring cells (does not work
on the infected cells)
– -IFN & -IFN: cause cells to produce antiviral
proteins (AVPs) that inhibit viral replication
• Gamma interferon produced by lymphocytes
– -IFN: causes neutrophils and macrophages to
phagocytize bacteria
Interferons (IFNs)
2 The infecting
virus replicates
into new
viruses.
5 New viruses released
by the virus-infected
host cell infect
neighboring host
cells.
6 AVPs degrade viral
m-RNA and inhibit
protein synthesis and
thus interfere with
viral replication.
1 Viral RNA from an
infecting virus
enters the cell.
3 The infecting virus also
induces the host cell to
produce interferon on
RNA (IFN-mRNA), which
is translated into alpha
and beta interferons.
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.
Figure 16.16
Interferons
• Effective for only short periods
• Have side effects when injected; high
concentration toxic
• Play a major role in infections that are acute
and short term (e.g. colds and influenza)
• Cannot stop the viral multiplication in virusinfected cells
• Some viruses (e.g. adenovirus) have
resistance mechanisms to inhibit AVPs
Chapter Review
1. Know the difference between the nonspecific
resistance vs. specific resistance and their
components
• Nonspecific resistance: defenses against any
pathogen regardless of species
Involved in
the first and the second line of defenses
• Specific resistance (immunity): resistance to a
specific pathogen based on lymphocytes and
the production of antibodies
Involved in
the third line of defense
Chapter Review
Figure 16.1
Chapter Review
2. Know how different components of the 1st
line of defenses provide nonspecific
resistance
• Mechanical factors: physical barriers to
entry or processes that remove microbes
from the body’s surface
– Intact skin
structure of intact skin; keratin;
dryness of the skin & periodic shedding of the
epidermis
Chapter Review
– Mucous membranes
inhibit the entrance of
many microorganism, but provide less protection
than the skin; mucus traps microbes and dust;
ciliary escalator move trapped microbes and dust
away from the lungs toward the throat
– Lacrimal apparatus
continuous washing by
tears keep microbes from settling on the surface
of the eye
– Saliva
dilutes and washes microbes off;
prevents microbial colonization
– Urine and vaginal secretions
flows out;
prevents microbial colonization
Chapter Review
• Chemical factors: substances made by the
body that inhibit microbial growth or destroy
them
– Sebum
forms protective film over the
surface of the skin; unsaturated fatty acids inhibit
the growth of certain pathogenic bacteria and
fungi
– Low pH (3-5) of skin
prevents growth of
many microbes
– Perspiration
washes off microbes from skin
Chapter Review
– Lysozyme in perspiration, tears, saliva, and tissue
fluids
breaks down cell walls of gram-positive
bacteria (peptidoglycan) and some gram-negative
cell walls
– Low pH (1.2-3.0) of gastric juice
destroy
most bacteria and bacterial toxins
• Normal microbiota
– Compete with pathogens for nutrients (microbial
antagonism); produce substances harmful to the
pathogen (e.g. bacteriocins); and alter conditions
(e.g. pH and O2 availability)
Chapter Review
3. Know how phagocytosis provides nonspecific
resistance for a host
• Phagocytosis: ingestion of microbes or
particles by a cell, performed by phagocytes;
many phagocytized microbes are killed by
lysosomal enzymes and oxidizing agents
– Shift in the predominant type of leukocytes occurs
in blood during the course of a bacterial infection:
• Granulocytes (esp. neutrophils)
macrophages
– Macrophages predominate in all phases of viral
and fungal infections
Mechanism of phagocytosis
Figure 16.8a
Chapter Review
4. Know how inflammation is induced, the three
stages of inflammation, and how it provides
nonspecific resistance for a host
• Local response of the body to injury triggered
by damage to the body tissues
– e.g. microbial infection, physical agents (heat,
electricity, or sharp objects), or chemical agents
(acids, bases, and gases)
• Formation of blood clots prevent spread of
infection; phagocytes destroy pathogens; repair
of damages tissues
Process of Inflammation
Figure 16.9a, b
Inflammation
Figure 16.9c, d
Chapter Review
5. Know how fever occurs and how it
provides nonspecific resistance for a host
• Most frequent cause of fever due to viral or
bacterial infection (and their toxins, esp.
endotoxins)
• Fever induced by release of interleukin 1
(IL-1) from phagocytes (review Fig. 15.6);
and release of alpha-tumor necrosis factor
from macrophages and mast cells
Chapter Review
• Considered a defense against disease up to a
certain point
– LI-1 induce production of activated T
lymphocytes (specific immunity)
– High body temperature intensifies the effect of
interferons
– Believed to inhibit growth of pathogens by
decreasing the availability of iron
– High temperature speeds up the body’s reactions
and tissue repair
Chapter Review
6. Know how complement system provides
nonspecific resistance for a host; also know
the 3 different pathway of the complement
system
• A defensive system consisting of over 30
proteins produced by liver; present in blood
and tissues
• Opsonization or immune adherence:
enhanced phagocytosis
Chapter Review
• Cytolysis: membrane attack complex
• Inflammation: attract phagocytes
• Classical pathway: initiated by an antigenantibody (Ag-Ab) reaction
• Alternative pathway: Activated by contact
between certain complement proteins and a
pathogen
• Lectin pathway: Production of lectins by
liver binds to carbohydrates on pathogens
and function as opsonin
Chapter Review
7. Know the three different types of interferons
(alpha-, beta-, and gamma-) and their
functions.
• Interferons: a class of similar antiviral
proteins produced by certain animal cells
after viral infection; interfere with vial
multiplication
• Host-cell-specific but not virus-specific
Chapter Review
• Alpha interferon (-IFN) and beta interferon
(-IFN) are produced by virus-infected host
cells to cause uninfected neighboring cells to
produce antiviral proteins (AVPs) to inhibit
viral replication if they get infected (does not
work on the infected cells) (Fig. 16.16)
• Gamma interferon (-IFN) is produced by
lymphocytes to cause neutrophils and
macrophages to phagocytize bacteria
Chapter Review
8. Know what these terms mean: susceptibility,
leukocytosis, leukopenia, opsonization and
chemokines