Di - Micro + Immuno Exam I: Bacterial Pathogenesis

Front 1

What is Pathogenicity?

Back 1

Ability to infect a susceptible host: requires the microorganism to survive and replicate within (colonize) the host

Front 2

What is Virulence?

Back 2

Ability to cause harm to the infected host: requires the microorganism to possess “virulence factors”, e.g. toxins, that damage the host

Front 3

What is an ID-50?

Back 3

dose of a pathogen that will infect 50% of a population

Front 4

What is a virulence factor?

Back 4

A virulence factor is a component or trait of a pathogen that allows it to cause disease in a susceptible host

Front 5

The T3S “injectisome” functions as what?

Back 5

a "hypodermic syringe"

Front 6

Pathogenicity is thought to be acquired in _____ _____ rather than through gradual evolution

Back 6

quantum leaps

Front 7

The Shigella virulence plasmid encodes a complete...

Back 7

T3S pathway and many of the T3S effectors

Front 8

The locus of enterocyte effacement “LEE” is a genomic ______ ______ that encodes a T3S system and intimin (eae), both required for enteropathogenic E. coli virulence.

Back 8

pathogenicity island

Front 9

What are Falkow’s Postulates?

Back 9

1. The gene(s) encoding the phenotype should be associated with pathogenic strains

2. Inactivation of the gene(s) results in a reduction in virulence.

3. Restoration of the gene(s) into the avirulent mutant reestablishes virulence.

Front 10

Diabetic Nephropathy -
What is it
How to prevent

Back 10

Glomerular sclerosis
mesangial expansion
=> glomerular HTN, dec. in GFR, nephrotic syndrome,
microalbuminuria, RF

to prevent -
ACE inhib
control BP
control glucose

Front 11

What are Fimbriae?

Back 11

Filamentous proteins on the surface of bacterial cells that may behave as adhesins for specific adherence

Front 12

Type 1 fimbriae (pili) bind specifically to what?

Back 12

mannose terminated glycoproteins on eukaryotic cell surfaces

Front 13

What bacterium causes dental caries and uses glycosyl transferase adhesins to attach to Salivary glycoprotein receptors on the pellicle of a tooth?

Back 13

Streptococcus mutans

Front 14

Streptococcus salivarius uses what adhesin to attach to the Buccal epithelium of the tongue?

Back 14

Lipoteichoic acid

Front 15

EPEC adhere to ______ ________

Back 15

Cellular “pedestals”

Front 16

What are the differences between cell invasins and tissue invasins?

Back 16

Tissue invasins promote cell destruction and spread of the organism

Cell invasins promote internalization of the pathogen into a cell, e.g. Yersinia invasin and Listeria internalin

(Some do both!)

Front 17

The periodontal pathogen Porphyromonas gingivalis
has an ______ _______

Back 17

internalin homolog

Front 18

macropinocytosis, also known as __________, is induced by effectors secreted Salmonella

Back 18

“membrane ruffling”

Front 19

Which are more potent, endotoxins or exotoxins?

Back 19

endotoxins

Front 20

What is Septic shock?

Back 20

Associated with overwhelming infection resulting in vascular system failure with sequestration of large volumes of blood in capillaries and veins; activation of complement and kinin systems and the release of histamines, prostaglandins, and other mediators may be involved

Front 21

What is Endotoxemia?

Back 21

Endotoxin in the blood

Front 22

Endotoxin activity
is carried by...

Back 22

Lipid A

Front 23

Endotoxin is
released upon
lysis or through
__________ of outer
membrane vesicles

Back 23

“blebbing”

Front 24

What are the effects of endotoxin?

Back 24

Binds to specific receptors on macrophages, B lymphocytes and other cells
- Stimulates release of lymphokines (e.g., IFN-g, IL-1, TNF-a, IL-6, histamine, prostaglandins)
- Stimulates growth of B cells (mitogenic) 

Fever (Pyrogenicity):
- Any elevation of the body temperature above normal; functions to speed up immune reactions and to slow bacterial growth 

Activation of alternative complement pathway

Front 25

Leukopenia followed by leukocytosis can occur as part of the circulatory system effects of _____

Back 25

endotoxin

Front 26

What are the two broad classes of exotoxins?

Back 26

Intracellular Targets
- A-B dimeric exotoxins (B, binding; A, active)
- B associated with absorption to cell surface and transfer of A across membrane
- once internalized, A enzymatically disrupts cell function
- Receptor-mediated endocytosis (exotoxin internalization)
- ADP-ribosylation of intracellular target host molecule

Cellular Targets
- Cytolytic exotoxins (usually degradative enzymes) or cytolysins
- hemolysis, tissue necrosis, may be lethal when administered intravenously

Front 27

What are the Three Major Types of Bacterial Cytolysins Based on Mechanism of Action?

Back 27

1. Hydrolyze membrane phospholipids (phospholipases); e.g. Clostridium; Staphylococcus 

2. Thiol(-SH)-activated cytolysins alter membrane permeability by binding to cholesterol; e.g. streptolysin O of Streptococcus; tetanolysin of Clostridium 

3. Detergent-like activity on cell membranes; rapid rate of lysis; e.g. Staphylococcus

Front 28

The Anthrax toxin has Three separate proteins:
1. Protective antigen (PA);
2. Edema factor (EF);
3. Lethal factor (LF)

What are the combinations they can be in, and what are the specific effects?

Back 28

EF + PA = increase in cAMP level resulting in edema (fluid accumulation)

LF + PA = death of host cells and ultimately death of host

Front 29

What does the Shiga toxin do?

Back 29

inhibits protein synthesis in humans

B-subunit binds to Gb3 glycolipid receptor; A-subunit prevents binding of aminoacyl-transfer RNA by cleaving 28S rRNA from 60S ribosomal subunit

Front 30

What does the Cholera toxin cause?

Back 30

profuse diarrhea

activates adenylate cyclase, resulting in increased cAMP and profuse diarrhea with outpouring of electrolytes (Na, K, bicarb), ultimately resulting in hypovolemic shock and death if no fluid/electrolyte replacement therapy

Front 31

What does the tetanus toxin cause?

Back 31

migrates from peripheral nerves to CNS pre-synaptic nerve endings, where it accumulates in vesicles and blocks the release of transmitters resulting in continuous stimulation of muscles, resulting in spastic paralysis with trismus (lockjaw) and spasms

Front 32

What do the botulinum toxins cause?

Back 32

inhibits release of acetylcholine at myoneural (muscle-nerve) junctions resulting in flaccid paralysis and death

Front 33

What does the Pertussis toxin cause?

Back 33

hypersecretion of mucus and paroxysmal cough and also inhibits leukocyte chemotaxis and activity

Front 34

Which toxin binds to elongation factor-2, inhibiting protein synthesis?

Back 34

Diphtheria toxin

Front 35

Heat-labile enterotoxins are Similar or identical to what other toxin?

Back 35

cholera toxin

Front 36

Heat-stable enterotoxins are similar or identical to what other toxin?

Back 36

cholera toxin, but with increased levels of cGMP leading to hypersecretion

Front 37

antiphagocytic substances include:

Back 37

1. Capsule (S. pneumoniae, H. influenzae, etc.)

2. K antigen (E. coli)/Vi antigen of S. enterica Typhi)

3. M protein/fimbriae (Group A Strep)

4. Protein A (S. aureus)

5. Slime layer (Pseudomonas)

6. O antigen (LPS of E. coli)

7. Agressins. "shooting first"

Front 38

After being phagocytized, parasites may avoid phagocytic killing by what methods?

Back 38

1. inhibiting phagolysosome fusion (Salmonella, Legionella, Chlamydia)

2. Surviving inside the phagolysosome (B. anthracis, M. tuberculosis, S. aureus)

3. Escaping from the phagosome (Rickettsia

Front 39

What are the Two major mechanisms by which pathogens escape the immune response?

Back 39

1. Antigen mimicry: The pathogen is naturally coated with antigens closely related to host constituents or “borrows” host constituents to coat itself with such that the immune system cannot distinguish between self and the pathogen

2. Antigenic variation: the pathogen changes its antigenic coat periodically to evade the ongoing immune response

Front 40

What 3 criteria define antigenic variation?

Back 40

1. avoidance of immune or niche selection, e.g. immune evasion, adaptation

2. multiphasic

3.gene conversion

Front 41

True/False?
Variation of an antigen within a species always occur by phase variation

Back 41

False


Variation of an antigen within a species DOES NOT always occur by phase variation, for example:
environmental regulation
Mutation

(Phase variation does not necessarily involve antigens)

Front 42

Most phase variation phenomena involve ______ structures

Back 42

surface

Front 43

Historically, phase variation was recognized by variation of _____ _____ (e.g. opacity) or of easily measurable phenotypes (e.g. motility)

Back 43

colony morphology

Front 44

Of the opaque vs transparent colony phenotypes of Group B Strep, which binds better to a susceptible cell?

Back 44

Transparent

Front 45

Concerning pili, phase variation mostly affects transcription at _______ ________

Back 45

major promoter

Front 46

glycosyl-transferases or sialyl-transferases are Enzymes that modify side groups of O-antigen. How are they able to produce variation?

Back 46

Phase variation

Front 47

In relation to phase variation, why are regulatory proteins advantageous?

Back 47

only one gene needs to phase vary to affect the expression of many genes

Front 48

_____ ______ is a widespread adaptation mechanism used whenever a bacterial population needs to produce variants at high frequency to survive

Back 48

Phase variation

Front 49

True/False?

Phase variation is always reversible

Back 49

True

Front 50

The Genetic basis of phase variation involves what mechanisms?

Back 50

Short sequence repeats and slipped-strand misrepairing

Homologous recombination

Site-specific recombination: Inversion of a DNA element. Insertion and excision of DNA elements

Front 51

What are the three levels of pilus variation in Neisseria gonorrhoeae?

Back 51

1. Transcriptional regulation: through PilA and PilB activator proteins.

2. Pilus subunit recombination

3. slipped-strand misrepair in pilC (tip adhesin)