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Chap 14 - 18
Selected Topics
in Immunology
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The Nature of Infectious Disease
• Infection is the invasion of the host by a
pathogen
• Disease results if the invading pathogen
alters normal body functions
• Disease is also referred to as morbidity
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The Nature of Infectious Disease
• Manifestations of Disease: Symptoms, Signs,
and Syndromes
– Symptoms
– Subjective characteristics of disease felt only by the
patient
– Signs
– Objective manifestations of disease observed or
measured by others
– Syndrome
– Symptoms and signs that characterize a disease or
abnormal condition
– Asymptomatic, or subclinical, infections lack
symptoms but may still have signs of infection
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The Nature of Infectious Disease
• Causation of Disease: Etiology
– Study of the cause of disease
– Germ theory of disease
– Disease caused by infections of pathogenic
microorganisms
– Robert Koch developed a set of postulates to
prove a particular pathogen causes a
particular disease
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Figure 14.7 Koch’s postulates
Agent not typically found
in healthy subjects
The suspected agent must be present
in every case of the disease.
Diseased subjects
Healthy subjects
Petri plate
Bacterial
colonies
The agent must be
isolated and grown
in pure culture.
Streaked plates
Injection
The cultured agent must cause
the disease when it is inoculated
into a healthy, susceptible
experimental host (animal or plant).
The same agent must
be reisolated from the
diseased experimental
host.
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The Nature of Infectious Disease
• Causation of Disease: Etiology
– Exceptions to Koch’s postulates
– Some pathogens can’t be cultured in the
laboratory
– Diseases caused by a combination of pathogens
and other cofactors
– Pathogens that require a human host
– Difficulties in satisfying Koch’s postulates
– Diseases can be caused by more than one
pathogen
– Pathogens that are ignored as potential causes of
disease
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The Nature of Infectious Disease
• Virulence Factors of Infectious Agents
– Pathogenicity
– Ability of a microorganism to cause disease
– Virulence
– Degree of pathogenicity
– Virulence factors contribute to virulence
– Adhesion factors
– Biofilms
– Extracellular enzymes
– Toxins
– Antiphagocytic factors
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Figure 14.9a Some virulence factors: Extracellular enzymes
Hyaluronidase and collagenase
Bacterium
Coagulase and kinase
Bacterium
Hyaluronidase
Coagulase
Clot
Clotting
protein
Epithelial
cells
Kinase
Collagenase
Collagen layer
Invasive bacteria
reach epithelial
surface.
Bacteria produce
hyaluronidase and
collagenase.
Bacteria invade deeper
tissues.
Bacteria produce
coagulase.
Clot forms.
Bacteria later produce
kinase, dissolving clot
and releasing bacteria.
Extracellular enzymes
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The Nature of Infectious Disease
• Virulence Factors of Infectious Agents
– Toxins
– Chemicals that harm tissues or trigger host
immune responses that cause damage
– Toxemia refers to toxins in the bloodstream that
are carried beyond the site of infection
– Two types
– Exotoxins
– Endotoxins
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Figure 14.9b Some virulence factors: Toxins
Exotoxin
Bacterium
Endotoxin
Exotoxin
Phagocyte
Phagocytized
Gram bacteria
Exocytosis
Endotoxin
Dead Gram
bacteria
Blood vessel
Bacteria secrete exotoxins, in this Cytotoxin kills host’s cells.
case a cytotoxin.
Dead Gram-negative bacteria release endotoxin (lipid A), which induces
effects such as fever, inflammation, diaarrhea, shock, and blood coagulation.
Toxins
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The Nature of Infectious Disease
• Virulence Factors of Infectious Agents
– Antiphagocytic factors
– Factors prevent phagocytosis by the host’s
phagocytic cells
– Bacterial capsule
– Composed of chemicals not recognized as foreign
– Slippery
– Antiphagocytic chemicals
– Prevent fusion of lysosome and phagocytic vesicles
– Leukocidins directly destroy phagocytic white
blood cells
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Figure 14.9c Some virulence factors: Antiphagocytic factors
Phagocytosis blocked by capsule
Incomplete phagocytosis
Capsule around
bacterium
Capsule around
bacterium
Bacteria
reproduce
Phagocytic
vesicle
Phagocyte
Lysosome
Antiphagocytic factors
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The Nature of Infectious Disease
• The Stages of Infectious Disease
– The disease process occurs following infection
– Many infectious diseases have five stages
following infection
– Incubation period
– Prodromal period
– Illness
– Decline
– Convalescence
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Modes of Infectious Disease Transmission
• Transmission is from a reservoir or a portal
of exit to another host’s portal of entry
• Three groups of transmission
– Contact transmission
– Direct, indirect, or droplet
– Vehicle transmission
– Airborne, waterborne, or foodborne
– Vector transmission
– Biological or mechanical
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Figure 14.12 Droplet transmission
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Figure 14.13 Poorly refrigerated foods can harbor pathogens and transmit diseases
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The Body’s Second Line of Defense
• Nonspecific Chemical Defenses Against
Pathogens
– Interferons
– Released by host cells to nonspecifically inhibit the
spread of viral infections
– Cause many symptoms associated with viral
infections
– Two types
– Types I (alpha and beta)
– Type II (gamma)
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Figure 15.7 The actions of alpha and beta interferons
Virus infects cell.
Virus
Doublestranded
RNA
Viral replication
in cell triggers
transcription and
translation of
IFN- or IFN-,
depending on
type of host cell.
IFN
gene
Time
passes
Meanwhile, the
infected cell dies,
releasing viruses.
Nucleus
mRNA
IFN
Infected cell
Infected cell
at a later time
Interferon is released,
diffuses to neighboring
uninfected cells, and
binds to receptors.
Interferon receptor
When the second
cell becomes infected
with viruses, doublestranded RNA of the
virus activates AVP.
Inactive AVP
Binding triggers
transcription
and translation of
inactive antiviral
proteins (AVPs).
AVP
gene
Doublestranded
viral RNA
Active AVPs
Time
passes
Ribosome
mRNA
mRNA
Inactive AVPs
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Uninfected
neighboring cell
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Same
neighboring
cell now protected
at the later time
Active AVPs degrade mRNA
and bind to ribosomes,
which stops protein
synthesis and viral
replication.
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The Body’s Second Line of Defense
• Nonspecific Chemical Defenses Against
Pathogens
– Complement
– Set of serum proteins designated numerically
according to their order of discovery
– Complement activation results in lysis of the
foreign cell
– Complement can be activated in three ways
– Classical pathway
– Alternative pathway
– Lectin pathway
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Figure 15.8 Pathways by which complement is activated
Classical pathway
Alternative pathway
Antigen
Mannose
C3b
Endotoxin and
glycoproteins
Antibody
Lectin pathway
Lectins
C3b Factors B,
D, and P
Complement
proteins
1, 2, 4
Complement cascade
Opsonization
Activation
(C3  C3a  C3b) Inflammation
C5 convertases
C5  C5a  C5b
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Inflammation
Membrane MDufilho
attack
complex and cell lysis
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Figure 15.9 The classical pathway and complement cascade
C3b opsonin
Cytoplasmic
membrane
Membrane
attack
complexes
Pathogen
Causes chemotaxis
of phagocytes
and inflammation
Antigen
Antibody
C1 becomes
an active enzyme
when it binds to
antibody-antigen
complexes.
This enzyme cleaves
C5 into C5a and C5b.
Acts as
opsonin
Enzymatic C1
Enzyme C1
splits molecules
of C2 and of C4.
C5b combines with C6, C7, C8,
and several molecules of C9
to form a membrane attack
complex (MAC). A MAC drills a
circular hole in the pathogen’s
cytoplasmic membrane,
leading to lysis of
the cell.
Enzyme
C3b combines
with the remaining
fragments of C2
and C4 to form a
third enzyme.
Fragments of C2
and C4 combine
to form a third
enzyme that
splits C3 into
C3a and C3b.
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Enzyme
Causes chemotaxis
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of phagocytes
and inflammation
Acts as
opsonin
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Figure 15.10 Membrane attack complexes
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Membrane attack complex
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The Body’s Second Line of Defense
• Nonspecific Chemical Defenses Against
Pathogens
– Complement
– Inactivation of complement
– Body’s own cells withstand complement cascade
– Proteins on many cells bind and break down
activated complement proteins
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Immunization
• Two Artificial Methods of Immunity
– Active immunization
– Administration of antigens so patient actively
mounts a protective immune response
– Passive immunization
– Individual acquires immunity through the transfer
of antibodies formed by immune individual or
animal
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Immunization
• Brief History of Immunization
– Chinese noticed children who recovered from
smallpox did not contract the disease again
– They infected children with material from a
smallpox scab to induce immunity
– This process known as variolation
– Variolation spread to England and America
but was stopped because of risk of death
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Immunization
• Brief History of Immunization
– 1796 – Edward Jenner discovered process of
vaccination
– 1879 – Louis Pasteur developed a vaccine
against Pasteurella multocida
– Antibody transfer developed when it was
discovered vaccines protected through the
action of antibodies
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Figure 17.1 Effect of immunization-overview
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Immunization
• Brief History of Immunization
– Many developing nations do not receive
vaccines
– Effective vaccines not developed for some
pathogens
– Vaccine-associated risks discourage
investment in developing new vaccines
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Immunization
• Active Immunization
– Vaccine types
– Attenuated (live) vaccines
– Use pathogens with reduced virulence
– Can result in mild infections
– Active microbes stimulate a strong immune
response
– Can provide contact immunity
– Modified microbes may retain enough residual
virulence to cause disease
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Immunization
• Active Immunization
– Vaccine types
– Inactivated (killed) vaccines
– Whole-agent vaccines
– Subunit vaccines
– Both safer than live vaccines
– Microbes don’t provide many antigenic molecules
to stimulate the immune response
– Often contain adjuvants
– Chemicals added to increase effective antigenicity
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Immunization
• Active Immunization
– Vaccine types
– Toxoid vaccines
– Chemically or thermally modified toxins used to
stimulate immunity
– Useful for some bacterial diseases
– Stimulate antibody-mediated immunity
– Require multiple doses because they possess few
antigenic determinants
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Immunization
• Active Immunization
– Vaccine types
– Combination vaccines
– Administration of antigens from several pathogens
– Vaccines using recombinant gene technology
– Attempts to make vaccines more effective,
cheaper, safer
– Variety of techniques used to improve vaccines
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Figure 17.2 Some uses of recombinant DNA technology for making improved vaccines-overview
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Immunization
• Active Immunization
– Vaccine safety
– Problems associated with immunization
– Mild toxicity most common
– Risk of anaphylactic shock
– Residual virulence from attenuated viruses
– Allegations that certain vaccines cause autism,
diabetes, and asthma
– Research has not substantiated these allegations
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Figure 17.3 The CDC's recommended immunization schedule for the general population
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Immunization
• Passive Immunotherapy
– Administration of antiserum containing preformed
antibodies
– Immediate protection against recent infection or
ongoing disease
– Antisera have several limitations
– Contain antibodies against many antigens
– Can trigger allergic reactions called serum sickness
– Viral pathogens may contaminate antisera
– Antibodies of antisera are degraded relatively quickly
– Limitations are overcome through development of
hybridomas
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Figure 17.4 The production of hybridomas
Mouse is injected
with antigen.
Long-lived myeloma cell
lines are grown in culture.
Plasma cells,
which secrete
antibodies,
are removed.
Antibodies
Hybridomas are formed
by mixing and fusing
plasma cells and myeloma
cells; they are long lived
and produce antibodies.
Hybridoma
Hybridomas are
placed individually
in small wells, and
their antibodies are
tested for reactivity
against the antigen.
A hybridoma that makes
antibodies that react
with the antigen is cloned.
Monoclonal
antibodies
Hybridoma clone
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Antibody (IgG, IgM) concentration (titer)
Figure 17.5 The characteristics of immunity produced by active immunization and passive immunotherapy
Passive
immunotherapy
Injection
Boosters
Active
immunization
Initial
inoculation
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