Chap.
13 Host-Microbe Relationships and Disease Processes
Pathogen parasite
capable of causing disease
Host
an
organism that harbors another organism
A. Symbiosis
- two different organisms living together.
1. commensalism
- one
organism benefits, the other is neither harmed or benefited. Many bacterial species fall into this category. Many individual bacterial species by themselves
don't provide direct benefit to the host.
2. mutualism
- both
partners benefit.
Ex.
ruminants (cud-chewing animals) and termites have microbial species that
break
down cellulose from plant cell walls so that it can be used for energy by the animal; this
relationship is essential for the ruminant.
Ex. Large numbers of E. coli live in the large intestine of humans. These bacteria release vitamin K, which we use to
make certain blood-clotting factors.
Ex.
Collectively an organisms natural flora protects the host by competing with
and
edging out many pathogens. This phenomenon is
called microbial antagonism.
3. parasitism
- host
is harmed, the parasite benefits; microbial parasites = pathogens. A narrow definition of parasites would include
only eukaryotic pathogens such as protozoa, helminths, and arthropods (ticks, lice,
fleas). A broader definition of this term
includes viruses, bacteria, and fungi.
B. Contamination
, Infection, and Disease A Sequence of Events
1. contamination
the
microbes are present.
2. infection
multiplication of any parasitic organism within or upon the hosts body; growth of
normal flora is usually not considered an infection; infection does not always cause
disease
3. disease
disturbance
in the state of health (state of relative equilibrium in which the body's organ systems
are functioning adequately); disease is characterized by changes in the host that
interfere with normal function.
C. Types of Flora:
(define and give specific examples for each)
1. Resident
flora
(= normal) - microbial species present in/on human body
throughout life; permanent species; coexist with humans in a stable relationship.
a. What does washing do to these guys? Reduces,
but does not eliminate.
b. What
parts of the body inhabited by normal flora? (external
vs. internal surfaces)
External - skin, conjunctiva
Internal - nose, mouth, intestinal tract,
vagina, urethra, ear
2. Transient
flora -
microbial species that can be cultured from body surfaces under certain circumstances, but
are not permanent residents.
a.
What
does washing do to these guys? Usually eliminates.
b. Why
aren't they part of the body's normal flora? Not well enough adapted to life on human
body.
c.
Noscomial
infections
(hospital-acquired infections) - Hospital workers have a large transient flora population
because of large number of pathogens they are exposed to every day (ex. pathogenic Staphylococcus aureus ); therefore, hospital
workers must be extremely careful about hand washing.
3. Opportunists
- microbial species that cause disease when the
proper opportunity arises, but are usually harmless; infections usually occur when
bacteria get into a place where they dont belong (ex. nonpathogenic bacteria that
are part of the normal flora of the colon go crazy when they get into the urinary tract.)
a.
Name
three opportunities for infection - breakdown in immune system, antibiotic treatment,
bioimplantation of
artificial devices (catheters, pacemakers, artificial joints);
b. What's
one reason for a vaginal yeast superinfection? Antibiotic treatments reduce numbers of
normal vaginal bacterial species; these bacteria usually keep the yeast Candida albicans in check.
D. Changing
Flora - Examples:
What
is one good reason why mothers should breastfeed? Its
not important just for the nutrients and the antibodies the baby receives in breast milk. While on breast milk, a baby's intestinal flora is
composed mostly of Bifidobacterium, which
metabolizes milk sugars into acetic and lactic acid.
These acids reduce the pH of the intestine, making it inhospitable to many
disease-causing microbes, most importantly those causing diarrhea. The intestinal flora changes when the baby is on
formula and the same protection is not provided.
What
is the effect of estrogen on the vaginal pH? What
effect does this have on the normal flora? Estrogen
increases the growth of lactobacilli which produce an acidic vaginal environment, making
it inhospitable to disease-causing microbes (ex. E.
coli from feces). Newborns have high estrogen levels from estrogen
that crosses the placenta. In a few weeks,
this estrogen level falls off. It doesn't
increase again until puberty. This is
important for when sexual activity could begin.
Pathogenicity
is
the capacity to produce disease. An
organisms pathogenicity depends on its ability to invade a host, multiply in the
host, and avoid being damaged by the hosts defenses.
Virulence refers to the intensity of the
disease produced by pathogens, and it varies among different microbial species. A pathogen must overcome the following seven
challenges if it is to survive on or in a human host & cause disease. Pathogenesis,
a microbe's ability to cause disease, depends upon its meeting all of these challenges. The seven challenges are:
A. Maintain
a reservoir
(a place in which a pathogenic microorganism is maintained between infections).
1. Human reservoirs - ex.
pertussis, measles, gonorrhea, common cold.
A person who is ill from an infection is a reservoir. Healthy people can also be reservoirs - called carriers.
incubatory
carrier
- in early symptomless stages of illness (most diseases have
specific
incubation periods associated with them; you may not realize you have an infection, but
you can still be contagious).
chronic
carrier
- person who harbors a pathogen for an extended period of time
without
becoming ill (ex. people who are HIV+ but
have not developed AIDS); this group also includes people who recover from an illness, but
harbor the pathogen (ex. Hepatitis B); people with herpes are also chronic carriers.
2. Animal
reservoirs
- ex. for rabies the animal reservoirs are skunks, possums, bats, raccoons, etc.; in this
case, the pathogen is spread through the bite of the rabid animal reservoir; insect
vectors can also be involved in spreading pathogens from animal reservoirs to humans - ex.
lyme disease (Borrelia uses deer and mice as a reservoir; a tick is
the vector). Zoonosis - a human disease caused by a pathogen
that maintains an animal reservoir. Mutations
& genetic variation can occur in the reservoir, causing new strains to emerge.
3. Environmental
reservoirs
- ex. soil, water, house dust; Clostridium tetani uses
soil - it's able to survive in this environment because of its ability to produce
endospores; Vibrio cholerae uses water.
B. Leave
its reservoir & enter the body of a human host.
Disease
transmission takes place when a pathogen leaves a reservoir and enters the body of a host. Most have a preferred portal of entry.
The number of pathogens that reach the portal of entry influences the likelihood of
successful disease transmission. The number
of microbes that must enter the body to establish infection in 50% of test animals is
expressed as the ID50 (infection dose). The LD50
(lethal dose) measures fatal infections - the number of microbes that must enter the body
to cause death in 50% of test animals. The
most common portals of entry for disease-causing microbes are external & internal body
surfaces: skin, conjunctivae (around eyes), nasal cavity & nasopharynx, mouth,
intestinal tract, vagina, urinary tract, etc. Others
include tissues below the skin in the case of an open wound or the placenta.
Transmission
can occur in several ways:
1. Human-to-human (communicable diseases - transmitted from
one person to another)
a. Respiratory
droplets expelled by coughing, sneezing, talking; ex. Bordetella pertussis
(whooping cough); more human diseases are transmitted by respiratory transmission than by
any other method.
b. Direct
body contact or person-to-person or horizontal transmission - transmission by touching,
kissing, sexual intercourse; includes STD's (sexually transmitted diseases); ex.
gonorrhea; herpes is most commonly spread by kissing or exchange of saliva (common in
young children).
c. Vertical
transmission - transmission from mother to infant; prenatal transmission - occurs across the
placenta; perinatal transmission - occurs
during passage through the birth canal; ex. STD's such as syphilis, gonorrhea, HIV,
Herpes.
d. Fecal-oral
route can involve direct contact (ex. a person does not wash his hands after
defecating and then shakes hands with someone); this transmission can also be by vehicles
such as water, food, fomites, or vectors (flies, etc.); (crops and water supplies may be
contaminated with fecal matter).
2. Airborne
Transmission - these
pathogens are hardy enough to withstand prolonged drying; can be transmitted across great
distances (greater than a meter); can remain viable in dust & reenter the air; ex.
Mycobacterium tuberculosis.
3. Vehicle
Transmission (objects such as food, water, fomites) Fomites
- inanimate objects such as cups,
towels, bedding, eating utensils, bedding, & handkerchiefs; ex. common cold viruses.
4. Parenteral
Transmission
- occurs when a biological arthropod vector introduces pathogens during a skin-penetrating
bite or when breaks in the skin or mucous membranes provide microbes with access to deeper
tissues; can also occur from penetration with a hypodermic needle; ex. HIV, hepatitis B
virus, Plasmodium (a protozoan that causes
malaria; mosquito vector), Clostridium tetani (causes tetanus when anaerobic conditions are
created in deep wounds)
5. Vectors - usually
insects or other arthropods (mosquito, tsetse
fly, tick, flea, lice, etc.)
a.
mechanical
vector - ex.
a fly lays its eggs in dog feces and then lands on your sandwich.
b. biological
vector
ex. the protozoan parasite that causes malaria goes through a stage in its life
cycle in the mosquito. Could bacteria use
biological vectors?
C. Adhere
firmly to the surface of the host's body and thereby colonize it.
Pathogens,
like normal flora, attach to specific types of target cells by means of adhesins (protein molecules that are very
specific for the receptors that they bind to on target cell surfaces); many adhesins are
molecular components of capsules or pili, thus these structures are are responsible for
the virulence of many strain of bacteria; some bacteria have a repertoire of adhesins -
this versatility makes them extremely virulent.
D. Invade
the body in order to enter cells or deeper tissues.
Only
a few pathogens cause disease by colonizing surfaces; most have additional virulence
factor that enable the pathogen to invade tissues (in other words, most pathogens are invasive - they penetrate the body's
surface to enter cells or deeper tissues). This
ability allows them to escape certain host defenses and to gain access to a nutrient-rich
environment that is free of competing microbes. Streptococcus produces the enzyme hyaluronidase that digests hyaluronic acid, a glue
like substance that helps hold the cells of certain tissues together. Some pathogens actually enter cells to live and
multiply inside them; they are called intracellular
pathogens. Ex. of intracellular
pathogenic bacteria - Rickettsias (ex. Rocky Mt. Spotted Fever) & Chlamydias. Some bacteria gain entry into cells by adhering to
surface receptors that fold into the cell during endocytosis.
Most
eukaryotic pathogens do not invade cells. An
example of one that does is Plasmodium (a
sproozoan protozoan that causes malaria); this parasite enter red blood cells.
E. Evade
the body's elaborate defenses against microbial invaders.
Here are just a few of the ways:
1. Protection Against Phagocytosis by White Blood
Cells.
a.
capsules
- make bacteria slippery and hard for wbcs to phagocytize; some bacteria are
virulent only if they produce a capsule; ex. Streptococcus
pneumoniae, Haemophilus influenzae.
b. surface
proteins
- interference with phagocytosis; ex. Streptococcus
pyogenes - produces M proteins - hairlike projections on the surface of its cell wall
(kind of makes them prickly); because of these projections, these guys can be phagocytized
only if antibodies bind to the bacteria, masking the M proteins.
c.
living
inside the phagocyte (white blood cell)
- only pathogens that possess special adaptations can survive the enzymes produced by the
phagocyte; ex. Mycobacterium tuberculosis -
survives because the phagocyte's enzymes cannot break through its waxy outer layer.
defenses. Ex. Staphylococcus
IgA
Proteases - enzymes
produced by bacteria that destroy the IgA class of antibody.
Ex.
Neisseria.
Streptokinase
dissolves blood clots so bacteria can spread to other tissues.
F. Multiply
within the body, perhaps producing toxic products or stimulating host reactions that cause
disease.
1. the
production of toxins (poisonous products that harm human cells and tissues ) &
exoenzymes.
2. stimulation of the body's defenses.
1. Exotoxins
§ Produced
by G(+) or G(-) bacteria.
§ Bind
to receptors on the surfaces of different types of cells.
§ Specific
for the cells they infect (ex. neurotoxins, such as tetanus & botulinum toxins effect
only nervous tissue. Enterotoxins, such as
those produced by Vibrio cholerae & Shigella
effect only epithelial cells lining the intestinal tract).
§ After
binding, the enzymes enter the cell & disrupt cellular function, usually by inhibiting
one specific metabolic reaction.
§ Some
exotoxins are unbelievably potent; ex. tetanus toxin - an amount about equal to the size
of the period at the end of this sentence can kill an adult!
§ Some
exotoxins enter the bloodstream, causing systemic
disease or toxemia (tissues throughout the body are affected).
§ Diseases
that result from the ingestion of a toxin are termed intoxications rather than infections. Ex. botulism food poisoning is the result of
injesting toxins made by pathogens.
§ Exotoxins
can be neutralized with special antibodies called antitoxins. Certain exotoxins can be modified in the lab by
treatment with heat or chemicals such as formaldehyde to produce toxoids; these molecules that have lost
their disease-causing properties, but still stimulate the immune system to produce
antitoxins (antibodies against toxin); vaccines can be produced from toxoids (ex.
tetanus).
§ In
most exotoxin-caused diseases, such as cholera, tetanus, E. coli diarrhea, shigellosis, & pertussis,
occur only if the bacteria multiply in the body. In
other diseases, such as botulism (food poisoning caused by Clostridium botulinum ), the toxin is produced
outside the body & is ingested with contaminated food called a food intoxication.
§ Some
are enzymes. Ex. Hemolysins
which lyse red blood cells. Alpha-hemolysin partially breaks down hemoglobin
(the oxygen-carrying protein in rbcs), leaving a greenish halo around colonies grown
on blood plates. Beta-hemolysin completely breaks down hemoglobin,
leaving a clear ring around colonies. Hemolysins
are produced by streptococci and staphylococci.
§ Leukocidins
produced
by stretptococci and staphylococci damage or destroy certain kinds of white blood cells. While most diseases are characterized by an
elevated white cell count, some may result in a decrease in numbers of wbc's.
§ May
be named after the part of the body they affect. Ex.
neurotoxin, enterotoxin
2. Endotoxins
§ Released
only by G(-) bacteria; all G(-) bacteria produce endotoxins.
§ Endotoxins
are lipopolysaccharides molecules (LPSs) in the outer membrane.
§ Its
effects include: fever, increased or
decreased #'s of wbc's, shock, death, diarrhea
§ Endotoxins
are not secreted by bacteria, but are released into the environment when the bacterial
cell dies.
§ Unlike
exotoxins, endotoxins are not proteins, so they are relatively heat stable.
§ Unlike
exotoxins, endotoxins don't stimulate the immune system to produce antibody; therefore,
toxoid vaccines would be useless.
§ Unlike
exotoxins, endotoxins are not specific for the cells they effect.
§ Normally
clinically significant only when large numbers of dying bacteria are circulating in the
bloodstream; paradoxically, agents that kill G(-) bacteria (antibiotics, etc.) may
actually increase endotoxin-mediated damage.
3. Stimulation of the Body's Defenses
Ex.
Streptococcus pneumoniae - when it multiplies in the lungs, phagocytes
(white blood cells) come to combat the infection; however, this bacteria is protected by a
capsule so more and more phagocytes arrive to help; dead bacteria & phagocytes
accumulate in the lungs, impairing normal gas exchange & making breathing difficult.
G. Leave the body and return to a reservoir &/or
enter a new host.
The
anatomic route through which a pathogen usually leaves the body of its host is called its portal of exit.
For most respiratory
pathogens, the portal of exit is the same as the portal of entry.
For most gastrointestinal
pathogens, the portal of entry is the mouth & the portal of exit is
the
anus.
STD's exit the same way they enter - across the mucous membrane surfaces of the genital tract.
Parenterally transmitted
pathogens exit the same way they enter - in the blood.
Acute
disease
develops rapidly and runs its course quickly
Chronic disease develops more
slowly, is usually less severe, and persists for a long
period.
Latent disease characterized by
period of inactivity (ex. Herpes)
Local infection confined to a
specific area
Systemic infection generalized
infection; affects most of the body.
Septicemia pathogens are present
in and multiply in the blood
Primary infection initial
infection in a previously healthy person.
Secondary infection follows a
primary infection (ex. a bacterial infection following a
cold).
Superinfection secondary infection that
results from the destruction of normal
microflora
and often follows the use of broad-spectrum antibiotics.
Mixed infection - caused by several species of organisms present at
the same time.
B. PRODROMAL
PHASE
(prodromos = forerunner) - Short period during
which nonspecific, often mild, symptoms such as malaise and headache sometimes appear. You feel like youre coming down with
something.
C. INVASIVE
PHASE
Period during which the individual experiences the typical signs and symptoms of
the disease (fever, nausea, rash, cough, etc.). During
the acme part of this phase, signs and symptoms
reach their greatest intensity. In some
diseases this phase may be fulminating (sudden
and severe), in others it may be persistent or chronic.
A period of chills followed by fever marks the acme of many diseases. The battle between pathogens and host defenses is
at its height during this stage.
D. DECLINE
PHASE Symptoms
begin to subside as the host defenses and the effects of treatment if being administered
finally overcome the pathogen. Secondary
infections may occur during this phase.
E. CONVALESCENCE
PERIOD Tissues
are repaired, healing takes place, and the body regains strength and recovers. Individuals no longer have disease symptoms, but
they may still be able to transmit pathogens to others.