What is a pathogen?
An organism that overcomes our defenses and causes damage
Most organisms are
not pathogenic and only become so in immunocompromised people.
What is Normal flora?
organisms on our body's surfaces that cause no harm
What are symbionts?
two organisms that live close together on a permanent basis.
Three types of symbiont relationships
mutualism, commensalisms and parasitism
Mutualism
both organism benefit in their symbiont relationship
Commensalisms
one organism benefits and the other is unaffected in their symbiont relationship
Parasitism
one organism benefits and the other is damaged in their symbiont relationship
What is colonization?
it is when a microbe is attached and growing/inhabits a person
When is colonization considered an infection?
only if the relationship is parasitic to the human
When is colonization considered a disease?
when there are obvious signs and symptoms associated with an infection
What is virulence?
the measure of the pathogenicity of an organism; how capable the
microbe is of causing an infection; a measure of how many infected
people are clinical and measure of how severe those symptoms are.
What is avirulent?
bacteria that is not capable of causing disease at all
What is a range of virulence?
some organisms are more virulent than others, even same type of
organisms have different virulent factors; ex. E. coli - some strains
cause diarrhea and others do not.
Three steps of course of infection:
incubation period, illness, convalescence; all three vary widely
depending on which pathogen causes the infection
Incubation period
time between initial contact with the pathogen and when symptoms occur
Illness
signs and symptoms; when you can see result of infection
Convalescence
recuperation and recovery
Types of bacterial infections
acute, chronic, latent
Acute
symopms last a short time
Chronic
infections develops slowly and lasts for a long time
Latent
infection is never completely eliminated
Principles of Infections Disease
Colonization, Virulence, Course of Infection, Types of bacterial
infections, Distribution of infection
Distribution of Infection
where in the body: Localized or systemic, bacteremia, toxemia,
viremia, septicemia (sepsis)
Systemic
infection is widespread throughout the body
Bacteremia
bacteria in the blood
Toxemia
toxins in the blood
Viremia
viruses in the blood
Septicemia
acute life threatening illness caused by microbes or their products
in the blood
What are Koch's postulates?
Robert Koch developed a system to determine if a microbe causes an illness
Name Koch's postulates:
1. Microorganism must be present in every case; everyone who has
symptoms must have same microbe present.
2. Must be able to grow the organism in pure culture from host blood/tissues.
3. Pure cultures of the organism must cause disease in susceptible
hosts (experimental infection); can be passed on.
4. Organism must be recovered from the experimentally infected host;
able to re-isolate original microbe.
Why were Koch's postulates modified into Molecular Postulates?
Because some organisms cannot be cultured in the lab; sometimes
culturing causes loss of virulence and some need an unknown nutrient
to grow in lab and ethics of doing experiments on humans (can't always
cause illness in a new host).
What is the concept of molecular postulates?
They deal with an organism's virulence factors; the characteristics
that allow an organism to be virulent/cause disease. Also don't have
the same problems Koch's postulates have.
What is virulence factor gene or gene product?
it is the protein made by DNA instructions that causes disease
Name the Molecular Postulates:
1. Virulence factor gene or gene product. Must be present in disease
causing strains but not in avirulent strains.
2. Introducing a virulence gene to an avirulent strain will make it
become virulent.
3. Virulence genes must be expressed during the disease; used while
having symptoms.
4. Antibodies or immune cells specific for the virulence gene
product should be protective.
Establishment of an infection
Adherence and Colonization
Adherence
when a microbe attaches to host cell surfaces
Fimbriae
pili that are used for attachment; sometimes have adhesins (protein)
on their tips
How do fimbria attach to host cell surfaces?
they attach to receptors on host cells; very specific to which type
of glycoproteins or glycolipids the bacteria can bind too so it limits
the cell type it can infect
Establishment of infection - colonization
microbe must be able to overcome the normal flora and host defenses
in order to divide and grow; after colonization some bacteria can
release toxins, etc. onto host cell that cause changes in the host cell
Types of invasion
Penetration of the skin and mucus membranes
Penetration of skin
happens through wounds or small tears; can't penetrate intact skin
Penetration of mucus membrane
1. induces phagocytosis in an epithelial cell by releasing molecules
that cause ruffling of host cell surface and then endocytosis
(considered non-professional phagocytes).
2. Uses antigen sampling cells. MALT uses M cells to sample areas of
the body; antigen uses these cells to get across the lumen to escape
phagocytes and cause disease.
M cells
an antigen sampling cell of the MALT; specifically in the intestines,
these cells sample lumen and pass material to the other side to give
to macrophages in the Peyer's patches
Avoiding Host Defenses
Hide in a host cell, inactivating complement, avoiding/surviving
phagocytosis, avoiding antibodies
Hide in a host cell
by becoming intracellular, microbes avoid antibodies, complement and
phagocytes; only risk is Cytotoxic T cell sampling and apoptosis
Inactivating complement
complement is only effective on Gram negative cells; MAC inserts into
LPS of gram neg. microbe
Serum resistant
gram positive organisms (no LPS) and some gram negative that
inactivate complement components
Avoiding Phagocytosis
C5a peptidase, killing phagocytes, capsules, Fc receptors
Surviving Phagocytosis
Escape the phagosome, prevent phagosome/lysosome fusion and have
mechanisms to survive the oxidative burse, low pH and degredative
enzymes of the phagolysosome.
C5a peptidase
breaks down the chemotaxic C5a, preventing phagocytes from being
called in.
Killing the phagocytes
microbes excretes toxins to form pores in host cell membranes
Capsules
slimy outer layer some bacteria have; make it hard for phagocytes to
hold on and engulf
Fc receptors
binds the Fc portion of antibody so that the Fab can't bind; limits
opsonization so does not aid macrophages in finding and phagocytosing
the microbe. (binds Ab backwards)
Avoiding antibodies
Iga protease, antigenic variation and mimic host cells
IgA protease
breaks down Iga so microbe cannot be trapped in mucus
Antigenic variation
microbe changes its outer surface molecules so any antibody that used
to be able to bind no longer will; new antibody must be made which
causes a delay time and microbe can continue to grow/spread
Mimic host cells
some microbes have an outer surface structure or molecules that
resemble host cells; they fool the immune system into treating the
microbe like self (camoflauge).
Exotoxins
proteins secreted outside the bacteria cell that cause very specific
damage to the host cells
Neutralization of toxins
immune system can make antibodies to the toxin that are protective;
sometimes toxin is fatal before Ab can be given, vaccination of toxoid
vaccines (contains fragment of the toxin) are given to create a ready
supply of the needed Ab.
Types of exotoxins
neurotoxins, enterotoxins, A-B toxins, membrane damaging toxins, superantigens
Damage to the Host
exotoxins, endotoxins and damage to Antibodies
Neurotoxins
exotoxins that damage the nervous system; anaerobic organism; ex. Botulism
Enterotoxins
exotoxins that damage the digestive tract; ex. Shigatoxin
A-B toxins
B portion of the toxin binds to the host cell and determines which
cell type the toxin will work on ; A portion is the enzymatic portion
that causes the damage.
Membrane damaging toxins
damage cell membranes causing them to lyse; hemolysins and phospholipases
Hemolysins
membrane damaging toxins that disrupt RBC membranes
Phospholipases
remove the phosphate heads from lipid bilayer, cause cell to lyse
Superantigens
exotoxins that avoid the specificity of the T cell response; bind
with a T cell receptor already bound to MHC II molecule; triggers a
mass release of cytokines from the T cell; stimulates 1 in 5 T cells;
massive release of cytokines causes systemic reaction with fever,
nausea, vomiting, shock, organ failure and possible death.
Toxic Shock Syndrome
ex. superantigen exotoxin; associated with Tampon use; S. aureus
grows in air pockets, causes TSST-1 (not septic shock but similar
symptoms); now sterilize with UV light radiation in manufacturing.
Endotoxin
is LPS of outer membrane of gram negative organisms. Lipid A portion
is toxogenic; symptoms are due to a large innate immune response; only
occurs if gram negative organism is broken down and LPS released into
host's system. Not a problem if LPS is intact/alive Gram neg. organism
Response to wide spread gram neg. infection in the blood
Generalized inflammation all over the body, causes leaky vessels,
clots in tissue to wall off infection widespread, dramatic drop in BP,
fever, etc; called septic shock and can be fatal; can also occur from
intestinal area surgeries
Damage due to antibodies
Antigen-antibody complexes and Cross-reactive antibodies
Antigen-antibody complexes
as antibodies bind antigen, they tend to clump together via
agglutination; if they are cleared fast enough by macrophages, they
settle in kidneys and joints which cause local inflammation that can
damage host tissues; can cause arthritis and kidney function/damage
Cross-reactive antibodies
occasionally antibodies made to foreign molecules will also
accidentally bind to our own self molecules causing an autoimmune response.