21 Host-Microbe Interactions, Part II: Pathogenic Interactions

Question 1

Define “pathogen”:

Answer 1

A microbe that can cause an infection and disease

Question 2

Define “primary” pathogen:

Answer 2

A pathogen that almost always causes a disease when present

Question 3

Define “opportunistic” pathogen. Who might be affected by these?

Answer 3

A pathogen that needs help to cause disease

An immunocompromised pt may be infected by opportunistic pathogens

Question 4

Define virulence:

Answer 4

A QUANTITATIVE measure of disease-causing ability (as measured by mortality rate, disease severity, etc.)

Question 5

A low-virulence microbe causes…

Answer 5

1. mild symptoms

2. no long-term effects

Question 6

A high-virulence microbe causes…

Answer 6

1. severe symptoms

2. high death rate

Question 7

What’s a virulence factor?

Answer 7

Any microbial product or structure that is REQ’D for it to cause disease

Question 8

What’s one way to quantify virulence of a microbe?

Answer 8

Look at the NUMBER of organisms needed to cause a disease > lower numbers = higher virulence

Question 9

Does a lower LD50 indicate higher virulence or lower virulence?

Answer 9

It indicates a higher virulence

Question 10

How can you determine whether a particular microbial component is a “virulence factor”?

Answer 10

Cause a microbe to become deficient in a particular component via mutation, and test whether it can still cause disease?

Question 11

Define localized infection:

Answer 11

When a microbe is restricted to a certain site in the body

Question 12

Define systemic infection:

Answer 12

When a microbe has spread throughout the body

Question 13

Define “asymptomatic (subclinical) infection”:

Answer 13

Infection w/ no obvious symptoms (or symptom so mild that they can escape diagnosis)

Question 14

Terms ending in “-emia” indicate…

Answer 14

the presence of a microbe in the bloodstream

Question 15

Terms ending in “-itis” indicate…

Answer 15

inflammation of (usually due to a microbe)

Question 16

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?

Answer 16

1. Be transmitted to and enter a suitable host
2. Avoid being removed after entry (via attachment)
3. Migrate to a site within host that can support growth
4. Overcome host defences and multiply at the preferred site
5. 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.

Question 17

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.

Answer 17

F

Bacterial virulence factors are req’d at each of the five steps

Question 18

Pathogen’s point of entry is partly determined by…

Answer 18

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

Question 19

T or F: Most pathogens have only ONE preferred portal of entry into the host.

Answer 19

T

Question 20

Most common portals of entry? (2)

Answer 20

1. Conjunctival membranes

2. Various body “tracts” (e.g. respiratory, uro-genital, intestinal, etc.)

Question 21

Define “infectious dose”:

Answer 21

of organisms needed to start an infection

Question 22

Name two specific ways the host can expel bacteria:

Answer 22

Mechanical actions, such as…

1. Urination
2. Gut peristalsis

Question 23

How do bacteria attach to host tissues to avoid being expelled? (3)

Answer 23

1. Pili (most common)
2. Bacterial cell surface proteins
3. Capsular polysaccharides

Question 24

T or F: Migration is an OPTIONAL process during the 5-step infection cycle of a bacteria.

Answer 24

T

Question 25

Another name for "migration" (of bacteria inside host).

Answer 25

"Invasion"

Question 26

What does bacterial invasion/migration (step 3) require?

Answer 26

Bacterial tissue-degrading ENZYMES that allow the bacteria to penetrate through cells

Question 27

List the strategies a bacteria uses to grow and survive inside the host? (2)

Answer 27

1. Obtain nutrients from the host | 2. Evade host's immune system

Question 28

List two ways bacteria can evade the immune sys of a host:

Answer 28

1. Bacterial capsule: blocks phagocytosis | 2. Bacterial "toxins": kills phagocytes and other host cells

Question 29

What stage of the bacterial infection cycle is absolutely required if the pathogenic bacteria is to have long-term survival?

Answer 29

The bacteria should be able to exit the host and transfer to a new host to repeat the cycle

Question 30

Respiratory pathogenic exit routes include...(2)

Answer 30

1. mucus | 2. saliva

Question 31

Intestinal pathogenic exit routes include...(1)

Answer 31

feces

Question 32

Sexually-transmitted pathogenic exit routes include...(2)

Answer 32

1. semen | 2. vaginal discharge

Question 33

T or F: The number of pathogens infecting a host is usually more than the number of pathogens exiting the host.

Answer 33

F Infection usually starts w/ smaller numbers of pathogens. Large numbers of bacteria are usually released.

Question 34

Is exiting from the host a passive process that results from bacterial numbers reaching a critical amount? Or exiting the host an active process?

Answer 34

Active - Bacteria want to be released so that they can spread to other hosts

Question 35

How do bacterial pathogens damage the host?

Answer 35

1. As a result of the host's immune response to the pathogen | 2. As a direct result of the pathogen's actions

Question 36

What're bacterial toxins?

Answer 36

Bacterial products which either... a. physically damages a host cell, or b. alters the host cell's metabolism

Question 37

Bacteria can damage the host directly via two types of bacterial toxins:

Answer 37

1. Endotoxins | 2. Exotoxins

Question 38

What're bacterial endotoxins?

Answer 38

Lipopolysaccharides (Lipid A part, specifically)

Question 39

Lipopolysaccharides are found in Gram ____ bacteria only.

Answer 39

negative

Question 40

When does the Lipid A component of the LPS get released?

Answer 40

When the bacteria die and their cells break apart

Question 41

T or F: LPS from diff gram neg bacteria differ in their ability to cause a biological effect in the host.

Answer 41

F All LPS has the same biological effect regardless of which gram neg species it comes from.

Question 42

What specifically occurs in the host in response to LPS? (2)

Answer 42

1. LPS causes immune sys to increase cytokine production. (Interleukin 1 > acts on hypothalamus > causes fever; TNF > lowers bp > shock) 2. Blood coagulation pathway gets activated and complement proteins get recuited

Question 43

Overall, what is the name of the complication that can occur due to LPS?

Answer 43

Toxic Shock

Question 44

Current limit of endotoxin in IV solns? (Note: This is considered "sterile")

Answer 44

0.25 endotoxin units (EU)/mL of IV soln

Question 45

What is the maximum human "pyrogenic dose"?

Answer 45

5 endotoxin units (EU) per kilogram | 5 EU/kg

Question 46

How can endotoxin be detected?

Answer 46

By using the "Limulus amoebocyte lysate" (LAL) assay > Amoebocytes will CLOT when exposed to LPS

Question 47

Amoebocytes used in the Limulus amoebocyte lysate assay (to detect LPS) is extracted from...

Answer 47

Limulus horseshoe crab

Question 48

What is the sensitivity of amoebocytes when detecting LPS?

Answer 48

0.05 endotoxin units (EU)/mL sensitivity

Question 49

T or F: Autoclaving is usually enough to destroy LPS.

Answer 49

F Autoclaving = 120ºC > not hot enough

Question 50

Two ways to remove LPS from biologicals after manufacture?

Answer 50

1. Heat to 250ºC for 30 min (autoclaving isn't enough) | 2. Affinity matrixes > immobilized resins that bind LPS

Question 51

Nonpyrogenic preparations do not contain _____ in enough quantities to cause fever

Answer 51

LPS

Question 52

What're exotoxins?

Answer 52

Toxic PROTEINS secreted by bacteria as they grow

Question 53

T or F: Large amts of exotoxin are needed to be potent.

Answer 53

F Exotoxins are highly potent in small amts

Question 54

When exotoxins act on eukaryotic cells, what can happen?

Answer 54

1. They can KILL the cell | 2. They can alter the METABOLISM of the cell

Question 55

Three general types of exotoxins produced by bacteria. What do each of them do?

Answer 55

1. CYTOTOXINS > blocks protein synthesis in eukaryotic cells > CELL DEATH 2. ENTEROTOXINS > causes hypersecretion of water from intestinal cells > DIARRHEA 3. NEUROTOXINS > interfere w/ NTs in nerves > MUSCLE PARALYSIS

Question 56

Name a toxin that is used therapeutically.

Answer 56

Botulinum Toxin (BoTox)

Question 57

Why can exotoxins act at sites far removed from the site of original infection?

Answer 57

Bc exotoxins = soluble, and thus can be carried by the bloodstream to diff sites throughout the body

Question 58

T or F: Exotoxins (but NOT endotoxins) can be chemically inactivated.

Answer 58

T

Question 59

What's the name of an inactivated exotoxin?

Answer 59

"Toxoid"

Question 60

T or F: If a bacteria produces endotoxins, then it won't produce exotoxins.

Answer 60

F Exotoxin production and endotoxin production are not mutually exclusive

Question 61

What type of bacteria can release endotoxins (lipid A) in the host?

Answer 61

Gram negative

Question 62

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.

Answer 62

positive

Question 63

T or F: Endotoxins are produced and released by bacteria, whereas exotoxins are liberated when the bacterium dies and the cell wall breaks apart.

Answer 63

F Other way around (Exotoxins = released, endotoxins = liberated after gram neg bacterial cell death)

Question 64

Endotoxin chemical composition = _____ Exotoxin chemical composition = ______

Answer 64

lipopolysaccharide protein

Question 65

"Bacterial pathogenicity is a multi-factorial process". What does this statement mean?

Answer 65

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]

Question 66

Why doesn't everyone respond to the same pathogen in the exact same way?

Answer 66

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

Question 67

Methods for lab diagnosis of bacterial infections:

Answer 67

1. Gram stain + microscopy 2. Methods NOT requiring growth (Serological tests, nucleic acid amplification tests) 3. Methods req'ing growth ("bacterial culture") 4. Other tests that may (or may not) be performed (antibiotic susceptibility testing, bacterial enumeration, genetic analysis for comparing diff strains)

Question 68

Advantages and disadvantages w/ gram stains.

Answer 68

1. Fast and easy | 2. Not v. sensitive

Question 69

What're gram stains good for?

Answer 69

For specimens that should be STERILE

Question 70

When're gram stains not useful?

Answer 70

If lots of normal flora are present

Question 71

Why don't diagnostic labs do gram stains on feces?

Answer 71

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

Question 72

What do serological tests (ELISA assays) look for? What's a disadvantage of them?

Answer 72

Antibodies in the blood of a pt that're produced against a specific bacteria Disadvantage: Doesn't distinguish b/w current and past infections

Question 73

What do nucleic acid amplification tests (NAAT) look for?

Answer 73

DNA sequences associated w/ diff bacteria

Question 74

PCR tests are best for...

Answer 74

1. bacteria that cannot be detected by other methods | 2. situations where other methods are too slow

Question 75

What do non-growth methods of bacterial detection require?

Answer 75

That we know exactly what bacterial species to look for.

Question 76

T or F: Non-growth methods of bacterial detection can answer the question, "Are there bacteria present?"

Answer 76

F

Question 77

T or F: Non-growth methods of bacterial detection can answer the question, "Is E. coli O157 present?"

Answer 77

T

Question 78

Among the methods for lab diagnosis of bacterial infections, which one can be used to screen for many diff bacterial species at once?

Answer 78

Bacterial cultures (methods req'ing growth)

Question 79

Among the methods for lab diagnosis of bacterial infections, which one cannot be used to screen for many diff bacterial species at once?

Answer 79

Methods that don't require bacteria growth for diagnosis (ELISA assays, NAATs)

Question 80

Most often used diagnostic method in microbio labs?

Answer 80

Methods req'ing growth ("bacterial culture")

Question 81

What type of assay is done for testing antibiotic susceptibility?

Answer 81

Disk diffusion assay

Question 82

What's genetic analysis useful for?

Answer 82

Tracking outbreaks or identifying sources of infection