Chapter 9
Infection
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Overview
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Eradication efforts
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Infection is 3rd leading cause of death in U.S.
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Successes and failures
Leading cause of death globally
Emergence of new infections
Increasing prevalence of known infections
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Drug resistance
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Microorganism/Human
Relationship
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Mutual relationship
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Normal flora
Relationship can be breached by injury
• Leave their normal sites and cause infection elsewhere
Opportunistic microorganisms
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Infection
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Colonization
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Invasion
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Attaches to host cells via adhesion molecules and
receptors: cell injury, alteration in function, or death
Multiplication
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Pathogens present: may infect others
Uses host nutrients/environment: tissue damage,
disease symptoms
Spread
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Migration through tissue, circulatory, or lymph
systems: disease
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Normal Colonization
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Produce enzymes that help digestion
Produce antibacterial factors
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Produce metabolites
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Prevent colonization by pathogens
Vitamin K
B vitamins
Maintained by system integrity/immune systems
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Pathogens if system integrity compromised
 Problem if immunocompromised/opportunistic
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Infection
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Factors influencing disease development
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Entry portal: spread is easy through blood and lymph
systems
Mechanism of action: how does it damage cells?
Infectivity: ability to enter and replicate
Pathogenicity: ability to produce disease
Virulence: speed of replication
Toxigenicity: production of toxins
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Classification
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Endemic
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Epidemic
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Diseases with relatively high, but constant, rates
of infection in a particular population
Number of new infections in a particular
population greatly exceeds the number usually
observed
Pandemic
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An epidemic that spreads over a large area (a
continent or worldwide)
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Clinical Course: Stages of
Infection
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Incubation
Prodromal
Invasion
Convalescence
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Clinical Manifestations of
Infectious Disease
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Variable depending on the pathogen
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Directly caused by the pathogen or indirectly caused
by its products
Fatigue, malaise, weakness, loss of concentration,
generalized aching, loss of appetite
Fever
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Resetting the hypothalamus
• Exogenous pyrogens
• Endogenous pyrogens
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Classes of Infectious
Microorganisms
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Viruses
Chlamydia
Rickettsia
Mycoplasma
Bacteria
Fungi
Protozoa
Helminths
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Pathogenic Defense Mechanisms
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Compete with normal flora
Produce toxins
Produce enzymes: avoid phagocytosis,
opsonization, destroy connective tissues
Avoid lysis: stop complement cascade by
degrading C3b
Paralyze cilliary activity
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Antigenic Variation
Altering the Surface Molecules
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Antigenic drift = mutation
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Antigenic shift
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Mutation of genes that express surface molecules
Unrecognized by B and T cells
Can happen quickly, even during an infection
Recombination (i.e., a human virus + chicken virus)
into a new virus
Gene switching
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Different genes turn on and off at different times
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Bacterial Virulence and Infectivity
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Bacteria must have iron to multiply
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Siderophores (iron receptors)
Presence of polysaccharide capsules
Suppression of complement activation
Bacterial proliferation rates can surpass
protective response
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Bacterial Virulence and Infectivity
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Toxin production
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Exotoxins
• Enzymes released during growth causing specific
responses
• Immunogenic
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Antitoxin production
Endotoxins
• Lipopolysaccharides contained in the cell walls of gramnegative organisms
• Pyrogenic effects
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Toxins
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Kill, damage, or alter cell function
Exotoxin: released from living microbe
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Neurotoxins
 Stimulate antibody production
 Can be converted to toxoid
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Endotoxin: from lysed gram-negative bacteria
Activates inflammatory response
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Bacterial Virulence and Infectivity
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Bacteremia or septicemia
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Presence of bacteria in the blood due to a failure
of the body’s defense mechanisms
Usually caused by gram-negative bacteria
Toxins released in the blood cause the release of
vasoactive peptides and cytokines that produce
widespread vasodilation
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Viral Infection
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Viruses are intracellular parasites
Do not have organelles necessary for
reproduction
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Replicate by “taking over” the metabolic systems
of host cell
May kill cell, coexist with cell, be killed by immune
system
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Viral Infection
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Attaches to host cell via protein receptors
Penetrates host cell
Releases genetic information into host
cytoplasm
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RNA viruses enter host nucleus
• Produce mRNA (new viral material)
• May produce provirus DNA (retroviruses: HIV)
DNA viruses enter host nucleus
• May integrate into host DNA; may make mRNA
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Viral Replication
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Translation of mRNA results in the production
of viral proteins
New virions are released through budding
Viral DNA that is integrated in host cell; DNA
is transmitted to daughter cells by mitosis
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Viral Infection and Replication
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Cellular Effects of Viruses
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Inhibition of host cell DNA, RNA, or protein
synthesis
Disruption of lysosomal membranes
Promotion of apoptosis
Fusion of infected, adjacent host cells
Alteration of antigenic properties
Transformation of host cells into cancerous
cells
Promotion of secondary bacterial infections
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Acquired Immunodeficiency
Syndrome (AIDS)
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Syndrome caused by a viral disease
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HIV
Depletes the body’s Th cells
Incidence
• Worldwide
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5 million per year
• United States
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About 31,000 cases per year
400,000 currently living with AIDS
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AIDS
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HIV-1
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Cause of HIV in Western Hemisphere and Europe
HIV-2
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Cause of HIV in Africa and Southeast Asia
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AIDS
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Effective antiviral therapies have made AIDS
a chronic disease
Epidemiology
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Blood-borne pathogen
Increasing faster in women than men
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Mechanism of Injury
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RNA virus (retrovirus)
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Stores genetic material on single-stranded RNA
rather than usual double-stranded DNA
 Carries an enzyme reverse transcriptase that
creates a double-stranded DNA version of the
virus
 New DNA becomes part of cell’s genetic material
and accelerates apoptosis
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HIV
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Structure
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gp120 protein binds to the CD4 molecule found
primarily on the surface of helper T cells
• CD4+ Th cells
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Typically 800 to 1000 cells/mm3
Reverses CD4:CD8 ratio
Co-receptors
• CXCR4 and CCR5
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Strains can be selective for these receptors; influences the
tropism of the target cells
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HIV Life Cycle and Target Points
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HIV
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Clinical manifestations
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Serologically negative, serologically positive but
asymptomatic, early stages of HIV, or AIDS
Window period
Th cells <200 cells/mm3
Diagnosis of AIDS is made in association with
various clinical conditions
• Atypical or opportunistic infections and cancer
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Phases of Disease
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Early phase
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Lasts about 2 weeks
Headaches, fever, flu-like symptoms
High level of virus in blood
Middle phase
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Lasts months to years
 Few symptoms
 Virus dormant in host DNA
 Few virus in blood but many Abs. Basis of testing.
 Continuous infection, death, and replacement of
CD4+ T cells likely by own Tc (CD8+ cells)
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Progression to AIDS
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Late phase
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If <400/cubic ml (normal, 1000), start treatment
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Rapid decline in CD4+ T cells
Patient weak, opportunistic infections begin
• Herpes, varicella, Mycobacterium (Tb), fungi, Pneumocystis
When CD4+ <200/cubic ml:
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Lymphoma
Cancer (Kaposi sarcoma)
Often fatal within a year
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Treatment
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HAART (highly active antiretroviral therapy)
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3 or more drugs: usually 2 that target reverse
transcriptase (fools DNA into incorporating it into new
strand, then halts DNA synthesis) and 1 that targets
viral protease (can’t cleave apart precursor proteins
so can’t make new viral proteins)
Not a cure; instead slows progression
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Expensive: $7000 to $10,000 per year
 Many side effects unpleasant
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Prevention
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Vaccines so far not very effective
Reduce risk behaviors
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Research
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Fusion inhibitors
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Integrase inhibitors
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Interferes with fusion of HIV and CD4+ cells
Worked in monkeys to slow disease progression;
have undergone clinical trials
Entrance inhibitors (co-receptor binding
inhibition)
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Uses monoclonal antibodies to inhibit binding to coreceptors
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Pediatric HIV and AIDS
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Presence of passive maternal antibody limits
the use of HIV antibody testing in infants up
to 15 months of age
CNS particularly vulnerable
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Developmental delays
 Impaired brain growth or acquired microcephaly
 Motor deficits
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Fungal Infection and Injury
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Large microorganisms with thick cell walls
Eukaryotes
Exist as single-celled yeasts, multicelled
molds, or both
Pathogenicity
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Adapt to host environment
• Wide temperature variations, digest keratin, low oxygen
Suppress the immune defenses
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Fungal Infection and Injury
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Diseases caused by fungi: mycoses
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Fungi that invade the skin, hair, or nails are
known as dermatophytes
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Superficial, deep, or opportunistic
Diseases produced are tineas (ringworm)
• Tinea capitis, tinea pedis, and tinea cruris
Deep fungal infections are life threatening
and are commonly opportunistic
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Fungal Infection and Injury
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Infection: Countermeasures
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Vaccines: prevent initiation of disease
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Primary response short lived
Boosters provide multiple secondary responses
• Increased memory cells
• Increased antibody
• Increased T cells
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Viral Vaccines
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Attenuated: weakened live virus (MMR,
varicella, polio/oral)
Inactivated: killed virus (hepatitis A,
polio/injected, influenza)
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Bacterial Vaccines
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Dead bacteria (pneumococcal pneumonia)
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Conjugated (to carrier proteins)
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Not very immunogenic in children
Increased immunogenicity
Haemophilus influenzae type B (Hib)
Toxoids
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Vaccine against bacterial toxins (DTaP, DT)
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Countermeasures
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Antimicrobials
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Inhibit synthesis of cell wall
Damage cytoplasmic membrane
Alter metabolism of nucleic acid
Inhibit protein synthesis
Modify energy metabolism
Antivirals
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Less successful because viruses use host
enzymes
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