Transcript CHAPTER 5 REQUIREMENTS FOR INFECTION

CHAPTER 5
REQUIREMENTS FOR INFECTION
© Professor P. M. Motta et al / Science Photo Library
WHY IS THIS IMPORTANT?
• This chapter introduces the mechanisms
involved in the infectious disease process.
• Understanding the requirements for infection
is critical to understanding prevention and
treatment of disease.
• Four of the five requirements for infection will
be discussed in this chapter.
OVERVIEW
REQUIREMENTS FOR A
SUCCESSFUL INFECTION
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•
•
•
•
Entry – getting in
Establishment – staying in
Defeat the host defenses
Damage the host
Exit the host and be
transmitted to another host
1) Entry
2) Colonization
3) Immune evasion
4) Growth / replication
5) Exit / disease
transmission
PORTALS OF ENTRY
(GETTING IN)
• Any point at which pathogens can
enter is called a portal of entry.
Entry via broken skin is referred to as
Parenteral inoculation.
PORTALS OF ENTRY
(GETTING IN)
MUCOUS MEMBRANES
• Mucous membranes are in direct contact with
the external environment.
• They allow pathogens to gain access into the
body.
• They are found in the:
– Respiratory tract
– Gastrointestinal tract
– Genitourinary tract
THE RESPIRATORY TRACT
• This is the most
favorable portal of
entry to pathogens
because we have to
breathe continuously.
• Pathogens can be
found on droplets of
moisture as well as
on dust particles.
THE GASTROINTESTINAL (GI) TRACT
• This is the second most favorable portal of entry for
pathogens since we have to eat and drink regularly.
• It has many barriers to infection but is still the entry point
for many pathogens.
THE GI TRACT
• The GI tract is also an important portal of exit.
– Pathogens can be found in fecal material after
leaving the body.
• The fecal-oral route of contamination is very
important in the infection process.
THE GI TRACT
• Helicobacter pylori infects the stomach and duodenum
of the small intestine.
• It survives the acidic environment of the stomach by
producing an alkaline halo around itself.
• It takes up residence in the mucus that lines the stomach
and duodenum.
• Infection with H. pylori is a known risk factor for
stomach and duodenal ulcers.
THE GENITOURINARY TRACT
• This portal of entry is more complicated than the
ones previously discussed.
• Urinary tract infections (UTIs) are more common in
women than in men.
• These types of infections cause major problems in
hospitals and clinical settings.
• Diseases of the reproductive tract are usually
sexually transmitted and are also part of this portal
of entry.
SKIN
• The skin is the largest organ in the body.
• The large surface area of the skin provides a
vast area through which microorganisms may
enter the body.
• Many microorganisms reside on the skin.
• Skin provides an impermeable barrier to most
microbes and must be broken to allow entry.
THE PARENTERAL ROUTE
• The term parenteral route refers to breaks in the
skin which permit entry of microorganisms.
• The parenteral route depends on injections, cuts,
or wounds, and surgical procedures to provide an
entry point.
• Insect bites can also allow entry of microbial
organisms.
• Insect transfer is referred to as vector
transmission.
ESTABLISHMENT
(STAYING IN)
• After entry into the host, pathogens must find a
way to stay in the body.
• Pathogens use structures, such as capsules or
fimbriae to attach to the surface of cells or tissues.
ESTABLISHMENT
(STAYING IN)
• Pathogens can use adhesins (glycolipids or
glycoproteins) to adhere to tissue.
• An example of this is the plaque found on
teeth.
– Plaque forms when a pellicle coats the tooth and
bacteria subsequently adhere to it.
– As many as 300 to 400 different types of bacteria
will adhere to each other building a biofilm on the
tooth. This is the plaque.
ESTABLISHMENT
(STAYING IN)
Spirochetes like
Treponema pallidum
(the causative agent
of syphilis)
corkscrew into
tissues.
© CDC/ Dr. David Cox
INCREASING THE NUMBERS
• Increasing the number of pathogens can
establish the infection in the host.
• Rapid growth and increased numbers of
pathogens can happen very quickly.
– Some pathogens can double their numbers in as
short a period as twenty minutes.
– An organism that doubles every twenty minutes
will become 1 x 1021organisms in just 24 hours.
• Some pathogens are more
infectious and virulent than others.
• We use the terms ID50 and LD50 to
characterize these differences
between pathogens.
INCREASING THE NUMBERS
• ID50 = infectious dose 50%
– The number of organisms required for 50% of the
host population to show signs of infection.
• LD50 = lethal dose 50%
– The number of organisms required to kill 50% of a
host population.
INCREASING THE NUMBERS
• Binary fission is the form of reproduction seen
in most bacteria.
One cell divides to yield two.
Two divide to become four and so on.
The number of bacteria can increase
very quickly.
INCREASING THE NUMBERS
• In viral infections, the number of viruses increases even
more dramatically.
• Virally infected cells will lyse (burst) and this releases
millions of viral particles.
– Each particle can infect a new cell.
– Each newly infected cell will produce millions of viral
Attachment
particles.
Infection
Release of
Viral Particles
(Cell Death)
Assembly of Viral Particles
Biosynthesis
DEFEATING THE HOST DEFENSES
• The body possesses powerful defense mechanisms.
• Pathogens must avoid, evade, or compromise these
defenses in order to survive and thrive.
• Pathogens can defeat host defenses in 2 ways:
– Passive defense – using built-in structures found on the
pathogen cell.
– Active defense – attacking the host defenses
VIRULENCE FACTORS
• Pathogens use virulence factors as part of the
infection process.
– They allow pathogens to survive and thrive in the
host.
– They make harmless organisms dangerous and
make dangerous organisms deadly.
PASSIVE DEFENSE:
Capsules
The main passive defense mechanism is the bacterial
capsule which inhibits phagocytosis by host cells.
• Cell wall
componentsDEFENSE:
can also contribute
passive
PASSIVE
CelltoWalls
defense.
– M proteins are found in the cell wall of streptococcus.
• They increase virulence by increasing adherence to host cells
• They can also inhibit phagocytosis.
• Can also cause toxic shock
-Protein A found on Staphylococcus aureus binds the “tail
end” of host antibodies to evade detection
PASSIVE DEFENSE:
Cell Walls
• Another method of passive defense is through
components of the bacterial cell wall.
– Mycolic acid is a waxy material found in the cell
walls of Mycobacterium species.
• It can inhibit phagocytosis and the entry of antibiotics.
ACTIVE
DEFENSES:
Enzymes
• Active
bacterial defenses
involve the
production of
extracellular enzymes which can:
– Increase protection against host defenses (e.g. coagulase).
– Enable the spread of infection by attacking and killing
host defensive cells (e.g. staphlyokinase).
•
•
•
•
•
EXAMPLES OF BACTERIAL
DEFENSIVE ENZYMES
Leukocidins – destroy white blood cells.
Hemolysins – attack red and white blood cells.
Coagulase – causes the formation of fibrin clots.
Kinases – break down fibrin and destroy clots.
Hyaluronidase and collagenase – break down connective
tissue and collagen
HIDING
FROM
THE
HOST
DEFENSE
• Pathogens can hide in host cells to avoid
the host immune response.
– Viruses are obligate intracellular parasites
and can easily enter host cells.
– Some bacteria use the host cell cytoskeleton
(microtubules and microfilaments) to get
into and move around a host cell.
– Other bacteria reside in phagocytic vesicles.
DAMAGING THE HOST
• Most of the damage to a host can be divided
into two causes:
– Damage that occurs because pathogens are present
and active. (Virulence)
– Damage that occurs because of host defense
mechanisms. (Collateral damage from the host
immune response)
DAMAGING THE HOST
• Damage to the host committed by the pathogen
can be direct or indirect
– Direct damage
• Is obvious and includes the destruction of host cells or
tissues
• Is usually controlled by the host immune response.
– Indirect damage
• Involves systemic infection as a result of toxin
production by the pathogen.
BACTERIAL TOXINS
• Bacterial toxins are:
– toxic
– Soluble in aqueous solutions
– Easily diffusible into blood and lymph which
causes distal pathology.
BACTERIAL TOXINS
• Bacterial toxins can produce fatal outcomes in
patients.
• They produce common symptoms such as fever,
shock, diarrhea, cardiac and neurological trauma,
and the destruction of blood vessels.
• There are 2 types of toxins:
– Exotoxins
– Endotoxins
EXOTOXINS
• Exotoxins are produced by and exported from certain
pathogens and then enter host cells.
• They are among the most lethal substances known.
• They are usually an enzymatic protein soluble in the blood
and lymphatic system.
EXOTOXINS
• Exotoxins rapidly diffuse into tissues where
they inhibit metabolic function.
• They are usually produced as pro-enzymes.
• Many genes that code for toxins are carried on
plasmids or spread by phages.
Phage encoded toxins:
•Cholera toxin
•Diphtheria toxin
•Botulinum toxin
•Shiga toxin
•Staphylococcal exfoliative toxin
and enterotoxins
•Streptococcus pyrogenic toxin
Plasmid encoded toxins:
Anthrax toxins
Clostridium enterotoxins
EXOTOXINS
• There are 3 types of exotoxins:
– Cytotoxins – kill cells
– Neurotoxins – interfere with neurological signaling
– Enterotoxins – affect the lining of the digestive
system.
EXOTOXINS
EXOTOXINS:
Anthrax Toxin
• Anthrax toxin is a cytotoxin.
• It is produced by Bacillus anthracis (a grampositive rod commonly found in pastures).
• It is made up of three parts which are:
– Produced separately within the pathogen
– Assembled outside the anthrax organism cell wall.
• It increases vascular permeability in host cells.
EXOTOXINS:
Diphtheria Toxin
• Diphtheria toxin is a cytotoxin.
• It is produced by Corynebacterium
diphtheriae.
• It is first produced in an inactive form.
• It inhibits protein synthesis in the host.
• A single molecule can kill a host cell.
EXOTOXINS:
Diphtheria Toxin
• The structure of diphtheria toxin is well
studied and composed of 2 chains called α and
β (A-B toxin).
• The β chain binds to the target cell and
facilitates the entry of the α chain.
• The α chain causes inhibition of protein
synthesis.
EXOTOXINS:
Botulinum Toxin
• Botulinum toxin is a neurotoxin.
• It is produced by Clostridium botulinum.
• There are seven forms of this toxin, all of
which inhibit the release of the
neurotransmitter acetylcholine.
– This disrupts neurological signaling of the skeletal
muscle.
– This disruption causes paralysis.
EXOTOXINS:
Tetanus Toxin
• Tetanus toxin is a neurotoxin.
• It is produced by Clostridium tetani.
• It causes loss of skeletal muscle control.
– Prevents muscle relaxation
– Causes uncontrollable convulsive muscle
contractions
– Lock jaw is an early symptom
EXOTOXINS:Vibrio Toxin
• Vibrio toxin (also known as cholera toxin) is an
enterotoxin.
• It is produced by Vibrio cholerae.
• It has a 2 chain polypeptide structure
– The β chain binds to the target cell
•The release of large
– The α chain causes cells to release large amounts of
amounts
of electrolytes
electrolytes.
causes potentially lethal
diarrhea and vomiting.
EXOTOXINS:
S. aureus Toxin
• Toxic shock syndrome is caused by the
enterotoxin from Staphylococcus aureus.
• This condition causes excessive loss of
electrolyte fluids.
• The loss of the fluids leads to hypotensive
shock.
ENDOTOXINS
• The damage to the host caused by endotoxins is very
different from the damage caused by exotoxins.
• Endotoxins are part of Gram-negative cell walls and
are released on the death of the host.
– Endotoxins are released in the form of Lipid A.
EXOTOXINS AND ENDOTOXINS
ENDOTOXINS
• Endotoxins cause the following symptoms:
–
–
–
–
–
Chills
Fever
Aches
Muscle weakness
Large amounts of endotoxins can cause
disseminated intravascular clotting (DIC).
ENDOTOXINS
• Exotoxins can elicit an immune response.
• Endotoxins do not elicit an immune response.
• Endotoxins can contaminate materials and
equipment.
• There are tests for endotoxin contamination.
VIRAL PATHOGENIC EFFECTS
• Viral host cell damage is referred to as a
cytopathogenic effect (CPE).
• The cytopathogenic effect of viruses occurs in
three ways:
– From viral overload
– From cytocidal effects (killing of host cells)
– From noncytocidal effects (damage caused by host
defense)
• Viral cytopathology can be seen
microscopically.
– Viral inclusions such as Negri bodies
can be seen in rabies infections.
– The presence of syncytia (large fused
cells)