L27 & 28

Question 1

What is a principal pathogen?

Answer 1

Likely to cause disease

In population sub-set that is otherwise normal

Question 2

What is an opportunistic pathogen?

Answer 2

Unlikely to cause disease

Needs some defect in adaptive/innate immunity to create infection

Question 3

What are the 4 points of Koch’s postulates?

Answer 3

= how we know microbes are the cause of a disease

1. X is found in all diseased people, but not in healthy people
2. X gets isolated and grown in culture
3. X is reproduced if put into susceptible animals
4. X can be isolated from the experimentally infected animals

Question 4

What are the 3 points of Koch’s MOLECULAR postulate?

Answer 4

= shows which factor of a microbe is important for creating disease phenotype

1. X gene that causes phenotype is also associated with pathogenic strains
2. Inactivation of X gene ↓virulence
3. Restore X gene fxn re-establishes virulence

Question 5

Define virulence, LD50, and ID50.

Answer 5

Virulence = tendency of an organism to cause disease
LD50 = lethal dose = amt of microbe that kills 50% of at risk population 
ID50 = dose to infect 50% of at risk pop

Question 6

Explain how disease reflects survival strategy.

Answer 6

If microbe could survive asymptomatically, it probably would
Instead symptoms reflect how the microbe must be multiplying and transmitting

Question 7

What are 3 changes to a microbe that would indicate emergence of new infections?

Answer 7

1. Shorter generation time - more replication (error prone), more changes to genotype, varied phenotypes
2. • new genetic elements (transposons)
3. Change in vector distribution

Question 8

What is the mechanism of Salmonella?

Answer 8

Normal commensals make SH2 = inflammation in response to presence of Salmonella (you think would be a normal/good immune response…)
Gut conditions SH2 –> S2O3 (thiosulfate)
Salmonella S2O3 –> S4O6 = its electron acceptor
- Created inflammation to use for its own survival

Question 9

What molecules are required for microbe establishment in the host?

Answer 9

Adherence molecules = adhesins
EX: e.coli w/ fimbrae
Also depends on the host receptor molecules present (host polymorphisms)

Question 10

How does N.meningitidis evade host immunity?

Answer 10

Binds factor H (complement breakdown)

Net: unregulated complement activation –> vascular damage

Question 11

What are the 2 mechanisms of cell invasion?

Answer 11

Zipper - binds to cytoskeleton receptors –> host surrounds & engulfs microbe
1. Invasin + beta integrins
2. Internalin + cadherin (Ca2+ dep)
Trigger - microbe binds cell signaling proteins –> engage actin cytoskeleton –> ruffling to engulf organism

Question 12

What are type 3 secretion systems?

Answer 12

How gram neg can inject virulence factors into host cytoplasm (membrane pin pricks)

Question 13

What is proptosis? Which organisms use this for avoiding phagocytosis?

Answer 13

Caspase programmed cell death –> ↑immune response to the site –> inflammation
Salmonella & Shigella
Normal tissue damage as bystander of inflam also allows more microbe entry

Question 14

How does Tersinia block phagocytosis?

Answer 14

YopH

Dephosphorylates focal adhesion molecules –> no anchoring –> no phagocytosis

Question 15

How does staph aureus block Ab mediated death?

Answer 15

Binds Fc region of IgG
Abs facing the wrong way:
- No opsonization
- Inactivate B cells

Question 16

What are 2 ways that microbes scavenge iron?

Answer 16

Siderophores

Transferrin binding protein

Question 17

What are examples of microbes that cause direct vs indirect damage to the host?

Answer 17

Direct: exotoxins
- Enter host cells to cause damage
Indirect: superantigens & endotoxin
- Endotoxin = lipid A potion of LPS (gram neg)

Question 18

How does diphtheria toxin work?

Answer 18

Toxin peptide cleaved –> A & B
B binds EGFRs - uptake into vacuoles - acidifies - B forms pore
A enters through pore & is enzymatically active
Stops protein synthesis –> cell death

Question 19

What is the mechanism of shiga toxin?

Answer 19

A & B subunits
B transported into ER
Inactivates 28S ribosomal subunit = no protein synthesis
Cell death, esp @ endothelium –> clotting

Question 20

What is the mechanism of TSS toxin? What disease results?

Answer 20

Cross links to activate T cells w/o MHC/antigen

Scarlet fever

Question 21

What happens with LPS binds TLR4?

Answer 21

↑NFkB
T cell activation w/ ↑antigen presentation
Massive cytokine release –> septic shock

Question 22

Walk through the entry, adherence, avoidance, and damage caused by Neisseria meningitidis.

Answer 22

Entry = mouth
Adherence = pili, opa proteins
Avoidance = fH binding, capsule, antigenic variance
Damage = LPS, complement activation