Burton’s Microbiology
for the Health Sciences
Section VII. Pathogenesis
and Host Defense Mechanisms
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Burton’s Microbiology
for the Health Sciences
Chapter 14.
Pathogenesis of Infectious
Diseases
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Chapter 14 Outline
• Introduction • Symptoms of a Disease
Versus Signs of a Disease
• Infection versus Infectious
Disease • Latent Infections
• Why Infection Does Not • Primary versus Secondary
Always Occur Infections
• Four Periods or Phases in the • Steps in the Pathogenesis of
Course of an Infectious Infectious Diseases
Disease
• Virulence
• Localized versus Systemic
Infections • Virulence Factors (Attributes
That Enable Pathogens to
• Acute, Subacute, and Attach, Escape Destruction,
Chronic Diseases and Cause Disease)
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Introduction
• The prefix “path” refers to disease.
• Pathogen - a microbe capable of causing
disease.
• Pathology - the study of the structural and
functional manifestations of disease.
• Pathogenicity means the ability to cause
disease.
• Pathogenesis refers to the steps or
mechanisms involved in the development
of a disease.
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Infection versus Infectious Disease
• An infectious disease is a disease caused by a microbe,
and the microbes that cause infectious diseases are
collectively referred to as pathogens.
• Infection is commonly used as a synonym for infectious
disease (e.g., an ear infection is an infectious disease of
the ear).
• Microbiologists reserve the word infection to mean
colonization by a pathogen; the pathogen may or may
not go on to cause disease.
• A person can be infected with a pathogen, but not have
an infectious disease.
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Why Infection Does Not Always Occur
• The microbe may land at an • The indigenous microbiota
anatomic site where it is may produce antibacterial
unable to multiply. factors (i.e., bacteriocins)
that destroy the pathogen.
• Many pathogens must attach
to specific receptor sites • The individual’s nutritional
before they are able to and overall health status
multiply and cause damage. often influence the outcome
of the pathogen–host
• Antibacterial factors may be encounter.
present at the site where the
pathogen lands. • The person may be immune
to that particular pathogen.
• Indigenous microbiota of
that site may inhibit growth • Phagocytes present in the
of the foreign microbe (i.e., blood may destroy the
microbial antagonism). pathogen.
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Four Periods or Phases in the Course of an
Infectious Disease
• The incubation period
- the time that elapses between arrival of the
pathogen and the onset of symptoms.
• The prodromal period the time during
which the patient feels “out of sorts” but does not
yet experience actual symptoms.
• The period of illness
-patient experiences the typical symptoms
associated with that particular disease.
• The convalescent period
-the time during which the patient recovers
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Four Periods or Phases in the Course of an
Infectious Disease
The incubation period :The time between the entry of a
pathogen into the body and the appearance of the first
signs and symptoms of disease.
The prodromal period :The early stage of a disease when
non-specific, mild symptoms begin to appear, but the
Example:
full-blown illness has not yet developed.
Disease Prodromal Symptoms
Measles Fever, cough, runny nose, red eyes
Influenza Muscle aches, low-grade fever, fatigue
COVID-19 (some) Sore throat, tiredness, mild headache
Chickenpox Fever, tiredness, loss of appetite
Examples of Incubation period
Disease Incubation Period
Influenza (Flu) 1–4 days
COVID-19 2–14 days (commonly 5–7 days)
Measles 10–14 days
Chickenpox (Varicella) 10–21 days
HIV/AIDS Weeks to months (for early symptoms)
Tetanus 3–21 days
Convalescence
Convalescence is the recovery phase after an illness,
when signs and symptoms fade and the body begins to
return to normal health.
What Happens During the Convalescent Period?
•The pathogen is eliminated or controlled.
•Symptoms disappear or significantly lessen.
•Tissue repair and healing occur.
•Strength and function are gradually restored.
•The person may still be contagious in some
diseases even if they feel better.
Localized versus Systemic Infections
• Localized infections
– Once an infectious process is initiated, the disease
may remain localized or it may spread; examples of
localized infections are pimples, boils, and abscesses.
• Systemic infections
– When the infection spreads throughout the body, it is
said to have become a systemic or generalized
infection; an example is miliary tuberculosis, caused
by Mycobacterium tuberculosis.
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Acute, Subacute, and Chronic Diseases
• An acute disease is one that has a rapid onset, and is
usually followed by a relatively rapid recovery; examples
are measles, mumps, and influenza.
• A chronic disease has a slow onset and lasts a long time;
examples are tuberculosis, leprosy, and syphilis.
• A subacute disease is one that comes on more suddenly
than a chronic disease, but less suddenly than an acute
disease; an example would be bacterial endocarditis.
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Symptoms of a Disease versus Signs of a
Disease
• A symptom of a disease is defined as some evidence of a
disease that is experienced by the patientsomething
that is subjective; examples are aches or pains, ringing
in the ears, blurred vision, nausea, dizziness, etc.
– There are symptomatic and asymptomatic diseases.
In a symptomatic disease, the patient is experiencing
symptoms. In an asymptomatic disease, the patient
is not experiencing any symptoms.
• A sign of a disease is defined as some type of objective
evidence of a disease (e.g., elevated blood pressure,
abnormal heart sounds, abnormal pulse rate, abnormal
laboratory results, etc.).
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Latent Infections
• Latent infections are
infectious diseases that go
from being symptomatic to
asymptomatic, and then,
later, go back to being
symptomatic.
– Examples include
syphilis and herpes virus
infections such as cold
sores, genital herpes,
and shingles.
An example of a cold sore
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Latent infection
The latent phase (or latency) is the stage of
infection where the pathogen is present inside the
body but remains inactive, not replicating at a
detectable level, and does not cause symptoms.
Latent Phase
1. No Symptoms
•The host shows no outward signs of illness.
•Often called a clinically silent period.
2. Dormant Pathogen
•The organism may hide in tissues or cells (e.g., nerve
cells, immune cells).
•It does not trigger immune responses strongly during
this phase.
3. May Reactivate
•Some latent infections can reactivate and cause illness
again, especially when:
• The immune system is suppressed (e.g., HIV, stress, chemotherapy).
• The host becomes elderly or malnourished.
4. Latent ≠ Cured
•Even if symptoms disappear, the infection is not
eradicated.
•Latency can persist for life in some cases.
Examples of Latent Infections
Disease Causative Agent Latent Behavior
Bacteria stay in lungs in a
Tuberculosis (TB) Mycobacterium tuberculosis
dormant form (latent TB)
Resides in nerve ganglia,
Herpes Simplex Virus HSV-1, HSV-2 reactivates as cold sores or
genital sores
Clinical latency phase (slow
Human Immunodeficiency
HIV/AIDS viral replication without
Virus
symptoms)
Virus becomes dormant in
Chickenpox/Shingles Varicella-zoster virus nerves, reactivates later as
shingles
Cysts in tissues may remain
Toxoplasmosis Toxoplasma gondii
latent for life
Stages of Syphilis
A syphilis chancre
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Primary versus Secondary Infections
• One infectious disease may commonly follow another; in
such cases, the first disease is referred to as a primary
infection and the second disease is referred to as a
secondary infection.
– Example: serious cases of bacterial pneumonia
frequently follow mild viral respiratory infections.
• During the primary infection, the virus causes
damage to the ciliated epithelial cells of the
respiratory tract; these cells are then unable to
clear opportunistic bacterial pathogens from the
respiratory tract, leading to the secondary
infection (pneumonia).
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Steps in the Pathogenesis of Infectious
Diseases
A common sequence of steps in the pathogenesis of
infectious diseases is
1. Entry of the pathogen into the body
2. Attachment of the pathogen to some tissue(s) within
the body
3. Multiplication of the pathogen
4. Invasion or spread of the pathogen
5. Evasion of host defenses (not affected by our host
defenses)
6. Damage to host tissue(s)
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Virulence
• The term virulent is sometimes used as a synonym for
pathogenic.
• There may be virulent (pathogenic) strains and avirulent
(nonpathogenic) strains of a particular species.
– Virulent strains are capable of causing disease;
avirulent strains are not.
– For example, toxigenic (toxin-producing) strains of
Corynebacterium diphtheriae can cause diphtheria,
but nontoxigenic strains of C. diphtheriae cannot.
Thus, the toxigenic strains are virulent, but the
nontoxigenic strains are not.
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Virulence, cont.
• Sometimes, the term virulence is used to express the
measure or degree of pathogenicity.
– Example: It takes only 10 Shigella cells to cause
shigellosis, but it takes between 100 and 1,000
Salmonella cells to cause salmonellosis. Thus,
Shigella is more virulent than Salmonella.
– Example: Some strains of Streptococcus pyogenes
(e.g., the “flesh-eating” strains) are more virulent
than other strains of S. pyogenes.
– Example: Some strains of Staphylococcus aureus
produce toxic shock syndrome, but other strains of
S. aureus do not. Those that do are considered more
virulent.
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Virulence Factors
• Virulence factors are attributes that enable pathogens to
attach, escape destruction, and/or cause disease.
• Virulence factors are phenotypic characteristics that are
dictated by the organism’s genotype. Examples are as
follows:
– Adhesins (ligands), special molecules on the surface
of pathogens, are considered to be virulence factors
because they enable pathogens to recognize and
bind to particular host cell receptors.
– Pili (bacterial fimbriae) are considered to be virulence
factors because they enable bacteria to attach to
surfaces, such as tissues within the human body.
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Adhesins and Receptors
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Examples of Virulence Factors
• The major
mechanisms by
which
pathogens
cause disease
are the
exoenzymes or
toxins that
they produce.
• Exoenzymes
released by
bacteria include:
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Virulence
Virulence Factor Function Example Organisms
Capsule Prevents phagocytosis by Streptococcus pneumoniae,
immune cells Klebsiella pneumoniae
Toxins Directly damage host tissues Clostridium tetani (tetanus
toxin), E. coli (Shiga toxin)
Enzymes Break down host tissues or Staphylococcus aureus
barriers (coagulase, hyaluronidase)
Adhesins Help bacteria stick to host cells Neisseria gonorrhoeae
(pili/fimbriae)
Biofilm Formation Protects bacteria from immune Pseudomonas aeruginosa,
attack and antibiotics Staphylococcus epidermidis
Flagella Enables motility and spread Helicobacter pylori
Antigenic Variation Changes surface proteins to Trypanosoma brucei,
avoid immune detection Neisseria gonorrhoeae
Siderophores Steal iron from the host for E. coli, Mycobacterium
bacterial growth tuberculosis
Intracellular survival Allows survival and Listeria monocytogenes,
Obligate Intracellular Pathogens
• Pathogens that must live within host cells in order to
survive and multiply are referred to as obligate
intracellular pathogens (e.g., Rickettsia and Chlamydia
spp.).
– Intraleukocytic pathogens (e.g., Ehrlichia spp. and
Anaplasma phagocytophilum) live within white blood
cells, causing diseases known as ehrlichiosis and
anaplasmosis.
– Plasmodium spp. (which cause malaria) and Babesia
spp. (which cause babesiosis) are examples of
intraerythrocytic pathogens; they live within red
blood cells.
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Facultative Intracellular Pathogens
• Facultative intracellular pathogens are capable of both an
intracellular and extracellular existence.
• Intracellular survival mechanisms of the pathogen
– Possession of a cell wall composition that resists
digestion (e.g., M. tuberculosis)
– Prevention of fusion of lysosomes with phagosomes
– Production of phospholipases that destroy the
phagosome membrane, thereby preventing
lysosome–phagosome fusion
– Other unknown mechanisms
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Capsules and Flagella
• Capsules and flagella are
considered to be virulence
factors.
• Examples of encapsulated
bacteria: Streptococcus
pneumoniae, Klebsiella
pneumoniae, Haemophilus
influenzae, and Neisseria
meningitidis.
• Flagella are virulence factors
because they enable
flagellated bacteria to invade
aqueous areas of the body; Photomicrograph of stained S. pneumoniae
they may also help the showing capsules (the unstained halos that
bacterium to escape surround the bacteria)
phagocytosis.
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Exoenzymes
• The major mechanisms by which pathogens cause
disease are the exoenzymes or toxins that they
produce.
• Exoenzymes released by bacteria include:
Necrotizing enzymes - exoenzymes that cause destruction of cells and tissues.
Kinases - exoenzymes that dissolve clots
Collagenase - breaks down collagen
Lecithinase - an exoenzyme that causes destruction of host cell membranes
Coagulase & Hyaluronidase - virulence factors that dissolve hyaluronic acid
and collagen, respectively, enabling pathogens to invade deeper into tissues
Hemolysins - are enzymes that damage red blood cells.
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Necrotizing Fasciitis
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Toxins
• Toxins are poisonous substances released by various
pathogens. There are two general types:
– Endotoxins
• Part of the cell wall structure of Gram-negative bacteria
• Can cause serious, adverse physiologic effects such as
fever and shock
– Exotoxins
• Poisonous proteins secreted by a variety of pathogens;
they are often named for the target organs that they affect.
• Examples: neurotoxins, enterotoxins, exfoliative toxin,
erythrogenic toxin, and leukocidins
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Tetanus Patient Displaying Opisthotonos
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Mechanisms by Which Pathogens Escape
Immune Responses
• Antigenic variation
– Some pathogens evade the immune system by changing
their surface antigensantigenic variation; examples,
Neisseria gonorrhoeae and Borrelia recurrentis.
• Camouflage and molecular mimicry
– Some organisms conceal their foreign nature by coating
themselves with host proteinslike camouflage (e.g.,
adult schistosomes).
• Destruction of antibodies
– Some pathogens produce IgA protease, an enzyme that
destroys some of the host’s antibodies (e.g., H.
influenzae).
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