Final Flashcards
1
Q
Salmonella Cell Biology
A
Gram -
Rod-like
Motile
2
Q
Salmonella diseases
A
Gasteroenteritis (typhimurium)
Typhoid fever (typhi)
Arthritis (Reiter’s syndrome)
3
Q
(S) SPI1
A
- Encodes T3SS ex. SopE
- Important for invasion of intestinal epi cells
- induces strong inflamm response via NAIP/NLRC inflammasome
- injects bacterial effector into host cytosol to initiate trigger mechanism via actin poly
4
Q
(S) SPI2
A
- Encodes T3SS ex. SifA
- Invasion of macrophages
- Important for intracellular growth
5
Q
(S) SopE
A
- mediates nt activation and exchange of Rho (GEF)
- short half life
- induces membrane ruffling
6
Q
(S) SipA
A
- binds directly to actin
- decreases [critical] for poly
- inhibits depoly
7
Q
(S) SptP
A
- blocks actin poly
- longer half-life than SopE
- reverses effects of SopE
- SopE+SptP=no ruffling
- SopE alone = no ruffling
- SptP alone = loss of F-actin
8
Q
(S) SifA
A
- virulence
- Sif formation
- SifA reside in vacuole
- SifA- released into cyto
9
Q
(S) Sif
A
Salmonella induced filament
- allows creation of own niche in vacuole
- SPI2- fail to induce Sifs
10
Q
(S) PhoP
A
- Two component regulatory system to control virulence
- regs LPS modifications
- changes expr >200 genes
- antimicrobial peptide resistance
- SPI2 activation
- PhoP- does not immunize
11
Q
(S) Prgs
A
PhoP repressed genes
12
Q
(S) Pags
A
PhoP activated genes
13
Q
(S) PhoQ
A
- two component reg system to control virulence
- bacterial PRR such that AMPs =PAMPs
14
Q
(S) PhoPc
A
- constitutively active = locked in active configuration
- no Prgs expr, only Pag
- virulence same as PhoP-
- PhoPc immunizes mice
15
Q
(S) Salmonella typhi vaccine
A
- Salmonella LPS has galactose
- vaccine is gal auxotroph
- bac are grown w gal, WT LPS syn
- in vivo, no gal, only rough LPS syn
16
Q
(S) Typhoid toxin - makeup
A
- 1 subunit homology CDT
- 2 subunits homology PT
- CDT= DNAse –>apop
- PT, PltA=pertussis-like toxin A –>ribosylation
17
Q
(S) Typhoid toxin - mechanism
A
-induces cell arrest in G0-G1 phase
18
Q
(S) Typhoid toxin - secretion
A
- made by bac growing in SCV
- assembled in periplasm
- secreted into lumen of SCV with help of TtsA
19
Q
(S) Typhoid toxin - export
A
- vesicle-carrier intermediates
- cannot intoxicate cell in which it is produced bc Ab to toxin protects cell
20
Q
(S) Rab29 and Rab31
A
- GTPases
- required for typhoid toxin export
21
Q
(S) Rab32
A
- GTPase
- prevents S. typhi from growing in non-human macrophages
- mediates anti-bac defense mechanism
22
Q
(S) GtgE
A
- T3SS in S. typhimurium
- protease that cleaves Rab32 (with SopD as GAP) and prevents recruitment to vacuole
- expr of GtgE allows S. typhi to grow in macrophages
23
Q
(S) Nramp
A
- manganese transporter
- makes 129 mice resistant to S. typhimurium
- starves bac of Mn2+ needed to grow
24
Q
(S) Aerobic vs fermentation
A
- 129 can transmit (supershedder) bc wins competition in gut w microbiota
- ttr gene cluster allows use of tetrathionate as e- acceptor
- tetrathionate req Cybb
25
(S) Cybb
- phagocyte oxidase
- makes tetrathionate for respiration
- produced by neutrophils that swarm gut during infection
26
(S) NAIP/NLRC4
- inflammasome
- activated by SPI1 inj of flagellin, needle and rod components
- caspase 1 cleaves pro-IL1 = IL1 --> neutrophil recruitment
27
(S) Outcompete microbiota
Salmonella➔SPI-1➔flagellin, rod, needle➔NAIP/NLRC4➔Caspase-1➔IL-1➔ neutrophil recruitment to gut➔inflammation➔ conversion of thiosulfate to tetrathionate➔ consumption of tetrathionate by ttr+ Salmonella➔ replication of Salmonella to high numbers in the gut➔ lots of bacteria shed in feces➔ transmission
28
(LP) Cell Biology
- gram -
- motile
- functionally obligate, but not technically
29
(LP) Disease
- replicates in alveolar macrophages
- inflammatory pneumonia
- no human --> human transmission
- high LD50
30
(LP) Dot/lcm T4SS
- Dot= defective for organelle transport
- Icm= intracellular multiplication
- main virulence factor
- used to inject effectors which create LCV
- targets host processes (generalist)
- T4SS = T3SS but can secrete nucleic acids
31
(LP) LCV
- legionella containing vacuole
- has ribosomes on surface
- takes 4h to form
32
(LP) effectors
- more than any other bac
- functional redundancies
- generalist ie provides diversity
33
(LP) B6 macrophages
- LP cannot replicate
- pyroptosis
- NAIP5 uses caspase-1 to cleave and activate pore-forming gasdermin D
34
(LM) Cell Biology
- cytosolic
- gram +
- Low G+C
- grows rapidly
- saprophyte
- food-borne pathogen
35
(LM) Disease
- infects adherent cells and macrophages
| - pregnant women and immunocompromised
36
(LM) Life cycle
- phagocytosis
- phagosome rupture
- bac surrounded by actin cloud/tail
- propelled from cell into listeriopod which is engulfed by neighbouring cells
37
(LM) LLO
- CDC family
- essential for pathogenicity
- encoded by hly gene
- allows escape from phagosome
38
(LM) PEST
- targets proteins for degradation in cyto so they don't lyse PM
- inactivation by phosphorylation or ubiquitinylation which targets for degradation by proteosome
39
(LM) prfA
- tx factor for operator binding of operon
- plasmids 10x less virulent bc 30 copies of plasmid incr # binding sites and sequester prfA so other virulence factors are not tx
- contains ActA, actin motility
40
(LM) Murine model
- mice immunized w LM resistant to LM, S and BCG 1-2 weeks later
- after 1 month, only resistant to LM
- non-specific immunity from macrophage activation
- specific immunity from CD8/4 T cells
- Ab plays no role
41
(LM) Reason for potent immunity
- entry and growth w/in AG presenting cells
- MHC class 1 pathway
- induction of innate immunity that promotes CMI
- lack of cell death
- lack of suppressive cytokines that block CMI
42
(LM) IFN-beta
- primary host gene induced
| - STING activation necessary
43
(LM) MDR
- multidrug resistance transporters
- play role in active efflux of antibiotics and toxic compounds
- repressed by TetR (tetracycline repressor)
- export c-di-AMP that activates STING and produces IFNB
44
(LM) c-di-AMP
- activates STING--> IFNB
| - when injected into tumor, induces tumor-specific CD8 that eliminate tumor
45
(LM) Vaccine vector
- highly manipulatable
- infects Ag presenting cells w/o killing
- potent inducer of CD8
- attenuated mutants (ActA-) retain immunogenicity and can be safely administered
- not neutralized by vector-specific immunity
46
(LM) actin based motility
- Actin poly essential
- inhib by cytochalasin D
- ActA req for motility
47
(LM) ActA
- In PrfA regulon
- has sec signal and TM domain (polar localization)
- activates Arp2/3 at bac surface by imitating WASP
48
(LM) Cofilin and capping prot
Cofilin = depolymerizing
| Capping prot = limits actin assembly to new filaments
49
(T) Cell Biology
-gram variable (+)
-non-motile
-thick, waxy coat
-mycolic acid and lipids
- thicker than normal g+
-acid-fast stain sp for
mycobac
50
(T) Disease
- infection via aerosol
- replication primarily in lungs
- bloody cough, weight loss, nausea, fever
51
(T) Antibiotics
- Isoniazid (INH)
| - Rifampin (RIF)
52
(T) Antibiotic resistance
- MDR TB (multiple drug resistant)
- resistant to INH and RIF
- curable w 2 yrs treatment
- XDR TB
- extensively resistant
- often not curable
53
(T) ESX-1
- T7SS
- disrupts/punctures phagosomal membrane
- req for intracellular replication and virulence
- arrests phagosome maturation
- provokes IFN response
54
(T) BCG
- attenuated mycobacterium
- given to children to protect against TB meningitis (not pulmonary)
- lacks ESX-1
- cures bladder cancer b/c incr in TNF
55
(T) Infection
- 1st 3wks unchecked
- CD4 and IFNG critical
- latent phase
- granulomas, stable standoff
- bac replication is balanced
- active phase
- extensive bac replication
- high inflamm & tissue destruction
56
(T) Granuloma
- method for body to contain bac it can't eliminate
- good sites for bac replication
- dead cells in center provide food for replication
57
(T) Central paradox
- The immune response is required to control bacterial replication (immunodeficiency in CD4 T cells or IFNɣ results in susceptibility to MTB)
- Immunopathology ultimately causes lung destruction and death (and enhances bacterial replication and transmission)
58
(T) IFN-G
- Important host factor to control MTB replication
- Induces Autophagy, Antimicrobial peptides, Nitric oxide
- Humans deficient for IL-12 or IFN-G signaling are highly susceptible for mycobacterial infection
- HIV induces decreases in DC4 count correlate with susceptibility to TB
- Majority antigen-specific T cells isolated from a TB patient produce IFN-G upon stimulation
59
(T) iNOS
- inducible nitric oxide synthase
- induced by IFN-G
- mediates resistance to MTB
60
(T) TNF-a
- Treated with anti-TNF-a causes 4-5x more incident of TB
| - Also causes a greater risk of disseminated and extrapulmonary disease
61
(T) CD8 Tcells
-CD8 T cell knockout causes a greater increase in TB infection
62
(T) IL-1
- IL-1 deficiency causes increased susceptibility to TB
| - No clear answer as to what IL-1 does to protect against TB
63
(T) Type I IFN
- Increased levels causes susceptibility to TB
- controls viral infections by inducing an anti-viral state to block viral replication
- confuses the immune system by inducing an anti-viral state rather than anti-bacterial immune response and increases susceptibility to TB
- HDT therapy inhibits type I IFN and promotes TB resistance (Expensive to administer)
- TB induces Type I IFN via activation of cGAS STING pathway
64
(T) Diagnosis
- Active TB
- X-ray
- Smear test
- Specific but not sensitive test that gives a rapid and inexpensive answer
- Culture test
- Tb grown in media. Slower and more difficult than smear (but more sensitive)
- Latent TB
- Tuberculin skin test
- Cannot be tested in individuals vaccinated with the BCG vaccine
- PDD is injected into the skin (purpified protein derivative)
- Bump forms on skin due to immune response
- Large bumps means infected with TB
- IFN-G release assay
- IGRA detects interferon gamma produced by T cells in response to MTB
- Does not give false positives
