21 Host-Microbe Interactions, Part II: Pathogenic Interactions Flashcards
Define “pathogen”:
A microbe that can cause an infection and disease
Define “primary” pathogen:
A pathogen that almost always causes a disease when present
Define “opportunistic” pathogen. Who might be affected by these?
A pathogen that needs help to cause disease
An immunocompromised pt may be infected by opportunistic pathogens
Define virulence:
A QUANTITATIVE measure of disease-causing ability (as measured by mortality rate, disease severity, etc.)
A low-virulence microbe causes…
- mild symptoms
2. no long-term effects
A high-virulence microbe causes…
- severe symptoms
2. high death rate
What’s a virulence factor?
Any microbial product or structure that is REQ’D for it to cause disease
What’s one way to quantify virulence of a microbe?
Look at the NUMBER of organisms needed to cause a disease > lower numbers = higher virulence
Does a lower LD50 indicate higher virulence or lower virulence?
It indicates a higher virulence
How can you determine whether a particular microbial component is a “virulence factor”?
Cause a microbe to become deficient in a particular component via mutation, and test whether it can still cause disease?
Define localized infection:
When a microbe is restricted to a certain site in the body
Define systemic infection:
When a microbe has spread throughout the body
Define “asymptomatic (subclinical) infection”:
Infection w/ no obvious symptoms (or symptom so mild that they can escape diagnosis)
Terms ending in “-emia” indicate…
the presence of a microbe in the bloodstream
Terms ending in “-itis” indicate…
inflammation of (usually due to a microbe)
All bacterial pathogens must complete a series of steps in order to successfully infect and cause disease. What’re these steps?
Which step is optional?
During which steps does the host begin to show symptoms of disease?
- Be transmitted to and enter a suitable host
- Avoid being removed after entry (via attachment)
- Migrate to a site within host that can support growth
- Overcome host defences and multiply at the preferred site
- Exit host and transfer to a new host to repeat the cycle
Step #3 is optional.
Symptoms of disease are noticed in steps 3-5.
T or F: Bacterial virulence factors are req’d at only ONE of the five steps required for bacteria to successfully infect a host and cause disease.
F
Bacterial virulence factors are req’d at each of the five steps
Pathogen’s point of entry is partly determined by…
the mechanism of transmission
e.g. if the mechanism of transmission is via food and water, then the point of entry is usually the intestinal tract
T or F: Most pathogens have only ONE preferred portal of entry into the host.
T
Most common portals of entry? (2)
- Conjunctival membranes
2. Various body “tracts” (e.g. respiratory, uro-genital, intestinal, etc.)
Define “infectious dose”:
of organisms needed to start an infection
Name two specific ways the host can expel bacteria:
Mechanical actions, such as…
- Urination
- Gut peristalsis
How do bacteria attach to host tissues to avoid being expelled? (3)
- Pili (most common)
- Bacterial cell surface proteins
- Capsular polysaccharides
T or F: Migration is an OPTIONAL process during the 5-step infection cycle of a bacteria.
T
Another name for “migration” (of bacteria inside host).
“Invasion”
What does bacterial invasion/migration (step 3) require?
Bacterial tissue-degrading ENZYMES that allow the bacteria to penetrate through cells
List the strategies a bacteria uses to grow and survive inside the host? (2)
- Obtain nutrients from the host
2. Evade host’s immune system
List two ways bacteria can evade the immune sys of a host:
- Bacterial capsule: blocks phagocytosis
2. Bacterial “toxins”: kills phagocytes and other host cells
What stage of the bacterial infection cycle is absolutely required if the pathogenic bacteria is to have long-term survival?
The bacteria should be able to exit the host and transfer to a new host to repeat the cycle
Respiratory pathogenic exit routes include…(2)
- mucus
2. saliva
Intestinal pathogenic exit routes include…(1)
feces
Sexually-transmitted pathogenic exit routes include…(2)
- semen
2. vaginal discharge
T or F: The number of pathogens infecting a host is usually more than the number of pathogens exiting the host.
F
Infection usually starts w/ smaller numbers of pathogens. Large numbers of bacteria are usually released.
Is exiting from the host a passive process that results from bacterial numbers reaching a critical amount? Or exiting the host an active process?
Active - Bacteria want to be released so that they can spread to other hosts
How do bacterial pathogens damage the host?
- As a result of the host’s immune response to the pathogen
2. As a direct result of the pathogen’s actions
What’re bacterial toxins?
Bacterial products which either…
a. physically damages a host cell, or
b. alters the host cell’s metabolism
Bacteria can damage the host directly via two types of bacterial toxins:
- Endotoxins
2. Exotoxins
What’re bacterial endotoxins?
Lipopolysaccharides (Lipid A part, specifically)
Lipopolysaccharides are found in Gram ____ bacteria only.
negative
When does the Lipid A component of the LPS get released?
When the bacteria die and their cells break apart
T or F: LPS from diff gram neg bacteria differ in their ability to cause a biological effect in the host.
F
All LPS has the same biological effect regardless of which gram neg species it comes from.
What specifically occurs in the host in response to LPS? (2)
- LPS causes immune sys to increase cytokine production.
(Interleukin 1 > acts on hypothalamus > causes fever; TNF > lowers bp > shock) - Blood coagulation pathway gets activated and complement proteins get recuited
Overall, what is the name of the complication that can occur due to LPS?
Toxic Shock
Current limit of endotoxin in IV solns? (Note: This is considered “sterile”)
0.25 endotoxin units (EU)/mL of IV soln
What is the maximum human “pyrogenic dose”?
5 endotoxin units (EU) per kilogram
5 EU/kg
How can endotoxin be detected?
By using the “Limulus amoebocyte lysate” (LAL) assay > Amoebocytes will CLOT when exposed to LPS
Amoebocytes used in the Limulus amoebocyte lysate assay (to detect LPS) is extracted from…
Limulus horseshoe crab
What is the sensitivity of amoebocytes when detecting LPS?
0.05 endotoxin units (EU)/mL sensitivity
T or F: Autoclaving is usually enough to destroy LPS.
F
Autoclaving = 120ºC > not hot enough
Two ways to remove LPS from biologicals after manufacture?
- Heat to 250ºC for 30 min (autoclaving isn’t enough)
2. Affinity matrixes > immobilized resins that bind LPS
Nonpyrogenic preparations do not contain _____ in enough quantities to cause fever
LPS
What’re exotoxins?
Toxic PROTEINS secreted by bacteria as they grow
T or F: Large amts of exotoxin are needed to be potent.
F
Exotoxins are highly potent in small amts
When exotoxins act on eukaryotic cells, what can happen?
- They can KILL the cell
2. They can alter the METABOLISM of the cell
Three general types of exotoxins produced by bacteria. What do each of them do?
- CYTOTOXINS > blocks protein synthesis in eukaryotic cells > CELL DEATH
- ENTEROTOXINS > causes hypersecretion of water from intestinal cells > DIARRHEA
- NEUROTOXINS > interfere w/ NTs in nerves > MUSCLE PARALYSIS
Name a toxin that is used therapeutically.
Botulinum Toxin (BoTox)
Why can exotoxins act at sites far removed from the site of original infection?
Bc exotoxins = soluble, and thus can be carried by the bloodstream to diff sites throughout the body
T or F: Exotoxins (but NOT endotoxins) can be chemically inactivated.
T
What’s the name of an inactivated exotoxin?
“Toxoid”
T or F: If a bacteria produces endotoxins, then it won’t produce exotoxins.
F
Exotoxin production and endotoxin production are not mutually exclusive
What type of bacteria can release endotoxins (lipid A) in the host?
Gram negative
Although exotoxins can be produced by both gram negative and positive bacteria, it’s mostly produced inside of gram _____ bacteria as part of their growth and metabolism.
positive
T or F: Endotoxins are produced and released by bacteria, whereas exotoxins are liberated when the bacterium dies and the cell wall breaks apart.
F
Other way around (Exotoxins = released, endotoxins = liberated after gram neg bacterial cell death)
Endotoxin chemical composition = _____
Exotoxin chemical composition = ______
lipopolysaccharide
protein
“Bacterial pathogenicity is a multi-factorial process”. What does this statement mean?
Diff virulence factors are needed to complete each step of the bacterial infection 5-step process.
[This means that one virulence factor is needed to enter the host, while a diff virulence factor is needed to overcome the host’s immune response]
Why doesn’t everyone respond to the same pathogen in the exact same way?
Because the host-pathogen interaction is multi-dimensional > differences in host, envir, and microbes can cause a diff in how two ppl respond to the same pathogen
Methods for lab diagnosis of bacterial infections:
- Gram stain + microscopy
- Methods NOT requiring growth (Serological tests, nucleic acid amplification tests)
- Methods req’ing growth (“bacterial culture”)
- Other tests that may (or may not) be performed (antibiotic susceptibility testing, bacterial enumeration, genetic analysis for comparing diff strains)
Advantages and disadvantages w/ gram stains.
- Fast and easy
2. Not v. sensitive
What’re gram stains good for?
For specimens that should be STERILE
When’re gram stains not useful?
If lots of normal flora are present
Why don’t diagnostic labs do gram stains on feces?
Bc normal feces has lots of bacteria present as part of its normal flora > it won’t help you in identifying the pathogenic bacteria present
What do serological tests (ELISA assays) look for?
What’s a disadvantage of them?
Antibodies in the blood of a pt that’re produced against a specific bacteria
Disadvantage: Doesn’t distinguish b/w current and past infections
What do nucleic acid amplification tests (NAAT) look for?
DNA sequences associated w/ diff bacteria
PCR tests are best for…
- bacteria that cannot be detected by other methods
2. situations where other methods are too slow
What do non-growth methods of bacterial detection require?
That we know exactly what bacterial species to look for.
T or F: Non-growth methods of bacterial detection can answer the question, “Are there bacteria present?”
F
T or F: Non-growth methods of bacterial detection can answer the question, “Is E. coli O157 present?”
T
Among the methods for lab diagnosis of bacterial infections, which one can be used to screen for many diff bacterial species at once?
Bacterial cultures (methods req’ing growth)
Among the methods for lab diagnosis of bacterial infections, which one cannot be used to screen for many diff bacterial species at once?
Methods that don’t require bacteria growth for diagnosis (ELISA assays, NAATs)
Most often used diagnostic method in microbio labs?
Methods req’ing growth (“bacterial culture”)
What type of assay is done for testing antibiotic susceptibility?
Disk diffusion assay
What’s genetic analysis useful for?
Tracking outbreaks or identifying sources of infection
