Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BABS3081 > Mid Sem - Important questions > Flashcards

Mid Sem - Important questions Flashcards

1
Q

What are the 3 steps in basic mechanisms of pathogenesis (strep)

A
  1. Invade and spread through tissue
  2. Production of toxins
  3. Provoke an autoimmune response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Explain how Strep invades tissue

A
  • bind to extracellular matric components or specific receptors
  • M protein attaches to keratinocytes in skin infection, delete C1 and C2 repeats, membrane cofactor protein CD46 is the receptor for M protein
  • Many other adhesions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Explain how strep evades phagocytic cells

A
  • evades recognision through proteases
    • protect strep from interacting with phagocytic cells by using C5a peptidase (serine protease which degrades C5a, a complement component that recruits and activates phagocytic cells)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How does Strep spread in tissue?

A
  • secrete digestive enzymes
  • Pus from strep is thin and runny because DNA and gibrin are degraded
  • Streptokinase activates protein plasminogen to plasmin which dissolves fibrin clots. 2 types (SLO and SLS), SLO is oxygen sensitive and enhances haemolysis under anaerobic conditions, SLS is oxygen stable and is non immunogenic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the hallmarks of toxin mediated disease?

A
  • Damage at sites distinct from primary site of infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How can strep produce toxin mediated disease?

A
  • exotoxins (Strep pyrogenic exotocins SPE, Spe A-J excluding D,E,I)
  • superantigens stimulate T cell proliferation (up to 20%)
  • also induce release of cytokines leading to inflammation and septic shock
  • responsible for the rash in scarlet fever as it has a direct effect on the capillary bed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the hallmarks of autoimmune based disease

A
  • unrelated disease post infection e.g. rheumatic fever
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How can strep produce autoimmune based disease?

A
  • antigenic mimicry (strep antigens hsare epitopes with human tissues, antibodies cross react with host tissue leading to damage)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the different adhesion factors and their associated gene (staph)

A
  • Fibronectin Binding Protein A (fnpA)
  • Fibronectin Binding Protein B (fnpB)
  • Collagen Binding Protein (can)
  • Fibrinogen Binding Protein (fbpA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

List the different invasion factors and their associated gene (staph)

A
  • Alpha (hla), beta (hlb), gamma (hlgA,B,C), delta (hld) haemolysin
  • Hyaluronidase (hysA)
  • Staphylokinase (sak)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe what alpha toxin (haemolysin) is, its potency and structure/how it works (staph)

A
  • Responsible for haemolysis, highest potency in damaging membrane
  • Monomer binds to membrane and forms heptamer with a central pore causing leaking of cellular content
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Explain the mechanism of action of B haemolysin, how is it encoded? (staph)

A
  • Damages membranes rich in sphingomyelin (not common in humans)
  • Encoded by a lysogenic bacteriophage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Explain the structure of delta haemolysin and its role (staph)

A

Very small peptide toxin (26 amino acids), regulatory role

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Explain what Gamma haemolysin is and the difference between its 2 components (staph)

A
  • Fast (HlgA, HlgB) and slow components (HlgC), slow is non toxic
  • Responsible mainly for severe necrotizing skin infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is Hyaluronidase and what does it do? (staph)

A
  • Enzyme for hyaluronic acid
    • This breaks down connective tissues and allows for
      dissemination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is Staphylokinase and what does it do? How is it encoded?

A
  • Plasminogen activator
  • Same as streptokinase
  • Encoded by lysogenic bacteriophages
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

List the different evasion factors and the gene that encodes them (staph)

A
  • Coagulase (coa)
  • Clumping factor (clfA)
  • Protein A (spa)
  • Leukocidin (lukR)
  • Super Oxide Dismutase (sod)
  • Catalase (katA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is Coagulase, what forms is it in and what is its mechanism of action? (staph)

A
  • 2 forms, Free and cell associated
  • Works by coagulating fibrogen to form fibrin which can be used to wall off infection and at as a barrier to PMNs
  • Forms Abscess
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is Protein A and how does it lead to evasion (staph)

A

Surface of staph aureus coated with protein A, has high affinity for Fc region of IgG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What proteins lead to toxin mediated diseases and what genes encode for them (staph)

A
  • TSST-1 (tstH)

- Enterotoxins A, B, C1-3, D, E, H (entA-H)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is TSST-1 and what is its mechanism of action? Which condition is it synthesised in, Aerobic or Anaerobic? (staph)

A

Protein responsible for Toxic shock syndrome, works by entering blood stream through tampon, Aerobic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is a pathogenicity island (staph)

A

A region of coding which determines virulence factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the difference between an antigen and a super antigen? (staph)

A

Super antigen also releases excess IL2 production, stimulated TNFa and induces shock as it can activate up to 20% of T cells whereas a normal antigen can only activate roughly 0.001%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the difference between Staph. Aureus and Strep. Pyogenes when causing Toxic Shock Syndrome

A

TSST-1 is from Staph aureus and enters blood stream through tampon, Strep pyogenes enters bloodstream as a whole bacteria and produces Spe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Explain the mechanism of action of Staph Food Poisoning

A

Enterotoxins injested, acts on receptors in gut initiating Emetic reflex after 4-6 hrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are examples of acquired virulence factors? How are they acquired? (staph)

A
  • Penicillin, Methicillin, vancomycin Resistance

- Acquired through use of antibiotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are potential risk factors for Uncomplicated and Complicated UTI’s?

A
  • Uncomplicated: Female gender, Older age, younger age

- Complicated: Indwelling catheters, Immunosuppression, Urinary tract abnormalities, Antibiotic Exposure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the most common bacteria in UTI’s?

A

UPEC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are host defence mechanisms that aim to prevent bacterial colonization of the urinary tract (mechanical and biological processes)

A 
- Mechanical
		○ Flushing urine
		○ Sphincter action
		○ Epithelial cell shedding
	- Biological
                ○ Immune system
30
Q

What are the initial events of UPEC infection? (what are the 2 requirements)

A
  • First requirement: Source of urinary pathogenic E.coli

- Second requirement: Entry into and colonization of the vagina and or the urethra

31
Q

Explain the importance of adhesion in UPEC

A

Adhesion important since there is constant discharge

32
Q

What is the mechanism of action for different Pili? (UPEC)

A
  • Type 1 pili (fimbrae) are produced by most strains of E.coli and bind to mannose residues attached to uroplakins (which are secreted by uro-epithelial cells).
    ○ Uroplakins over 90% of apical surface of
    mammalian uro-epithelium
    ○ Type 1 pili has Fim H (adhesion tip), Fim zG
    and Fim F (structural proteins) as well as Fim
    A (encodes Pilus rod)
  • P-pili are primarily associated with UPEC strains and recognize the same receptor using globobiose (a pap gene cluster) which encodes proteins for the synthesis and assembly of p pili
  • P-pili undergo phase variation
33
Q

What is the mechanism of action for non p-pili UPEC strains

A
  • Non p-pili UPEC use a variety of other adhesions such as afimbral adhesions
    ○ Receptor for Afa adhesion is unknown
    ○ Dr adhesion recognizes Dr blood group
    antigen
34
Q

Explain what Phase variation is (UPEC)

A
  • Changes occur in response to multiple environmental signals such as temperature, level of glucose, concentration of certain amino acids
  • May allow evasion of host immune response
35
Q

What are Siderophores? How do siderophores compete with the mammalian immune system and bacteria? (UPEC)

A
  • Siderophores are proteins used to retrieve and compete for iron which is vital for bacteria
  • Enterobactin removes iron from transferrin, this is intercepted by siderocalin which means bacteria have to produce alternative siderophores such as salmochelin
36
Q

How does UPEC colonization lead to the strong inflammatory response responsible for signs and symptoms of UTI’s

A

LPS from bacteria cause inflammatory response as well as the P-pili on the outer surface

37
Q

List and describe the different UPEC exotoxins

A
  • A Haemolysin (HylA)
    ○ Lyses erythocytes
    ○ Contributes to inflammation, tissue injury and
    impaired immune responses
    ○ At high levels lyses host cells, at low levels
    stimulated cytokines and superoxide
    production by renal cells
    § Leads to kidney damage and
    inflammation
  • Cytotoxic necrotizing factor CNF1
    ○ Modules polymorphonuclear leukocyte
    function
    ○ Facilitates UPEC survival during the cause
    inflammatory response
38
Q

What are virulence factors associated with more serious UPEC infection

A
  • Capsular polysaccharide (K antigen)

- Protects bacterium from phagocytosis and serum killing -> impaired host defence

39
Q

Explain the sequence of events in the bladder in those with

UPEC UTI infections as well as advantages of each stage

A
  • Binding: binds and invades superficial epithelial cells of bladder mediated by type 1 pili via FimH
    • Invasion: Attachment of UPEC, invasion of epithelial cell, localized actin rearrangement
      ○ Membrane engulfs bacteria, UPEC grow rapidly and divide.
      ○ Formation of intracellular bacterial communities (IBCs)
      § Advantage: hide and survive
    • Middle IBC’s
      ○ Many biofilm properties
      § Community behaviour
      § Associated with long-term pesistence
      § Resistance to antibiotics
      § Resistance to human immune effects
      ○ Phenotypic switch, shortening of bacteria
    • Late IBC’s
      ○ Bacteria on edge of biofilm detach and differentiate into typical rod shape
      ○ Become highly motile
    • Late IBC’s and fluxing
      ○ Motile bacteria swim to edge of cell and burst out into bladder lumen (fluxing)
      Leads to spread over epithelium and reattachment at different points
40
Q

Why is UPEC persistence high in the bladder?

A

The fluxing cycle may invade and remain dormant for months making it undetected and hard to know when it is completely gone

41
Q

How is EPEC defined? (by the presence of…)

A

Presence of LEE and Bfp

42
Q

What is the difference between a typical EPEC and an atypical EPEC?

A

Typical EPEC has bfp atypical does not

43
Q

How does EPEC attach and efface lesions? (3 stages)

A
  • Stage 1: Non-intimate association via bundle forming pili
    ○ Bacterial cells aggregate together
  • Stage 2: Type 3 secretion of Tir and other effectors
    ○ Assembly of Type III secretion system which
    leads to intimate adherence
    Stage 3: Intimate adherence, Attaching and Effacing lesion
44
Q

What is a Bundle forming pili? How is It regulated? What is it’s importance in virulence (EPEC)

A
  • Mediates bacterial-bacterial interaction -> forming of microcolonies
  • Transcription of bfp regulated by Per A
  • Encoded by PerABC operon on EAF plasmid
  • Per B and C required for full transcriptional activation of the bfp gene cluster
  • Importance in virulence: mediated initial adherence to host through n-acetyl-lactosamine receptors on host cell
45
Q

What does each Lee operon encode? (EPEC)

A
  • LEE1-3
    ○ Encodes type 3 secretion system (TTSS) for
    translocating bacterial proteins towards the
    enterocyte
  • LEE4
    ○ Encodes esp genes (EPEC secretion proteins)
    espADB encode for translocator proteins that form
    a conduit through which T3SS delivers effector
    proteins to host cell
  • LEE5
    ○ Encodes genes necessary for bacterium-host cell
    intimate adhesion (eae: encodes adhesin intimin,
    tir: Translocated intimin receptor)
46
Q

How do EPEC secrete effector proteins into host cells using the T3S system?

A
  • Inner and outer ring components assembled
  • EscF polymerized and assembled into outer and inner rings
  • EspA filament secreted via type 3 secretion system and attached to the tip of the needle
  • Formation of a hollow filament
  • Translocation effector proteins enter into host cell
47
Q

What is the role of T3SS in intimate adherence? (EPEC)

A
  • Intimin used to cause intimate binding, however there is no natural receptor for it
  • Tir (translocated intimin receptor) is translocated into host cell via T3SS and acts as a receptor for intimin
48
Q

How does Tir activate an actin signaling cascade? (EPEC)

A
  • Tir becomes tyrosine phosphorylated in host cell plasma membrane
  • Binds to adaptor protein
    ○ Nck
  • Nck recruits N-WASP or a WIP-N-WASP complex
    ○ Triggers activation of the Arp2/3 complex
  • Actin is assembled in a pedestal formation
49
Q

How does EPEC cause diarrhea?

A
  • Damage to absorptive apical surface causes failure to absorb water
  • Injected effector proteins disrupt tight junctions
    ○ Increases permeability of mucosal enterocyte tight
    junctions
    ○ Activation of NFkb
    ○ Activation of IL-8 cytokine
  • Recruitment of polymorphonuclear neutrophils (PMNs)
50
Q

Explain the pathogenesis of EHEC

A
  • Similar to EPEC
  • LEE pathogenicity island present
  • Forms A&E lesions
  • Produces large amounts of shiga-like toxin which acts on sites remote from intestine
51
Q

Explain EHEC and adhesion?

A
  • No bfp
    ○ Uses wide variety of adhesions
  • Mediate similar binding and actin rearrangements as EPEC
  • Use Intimin (eae) adhesion to intimately attach to host cells
52
Q

Explain actin signalling cascade activated by EHEC during pedestal formation

A
  • Tir localizes to the plasma membrane
    ○ NOT tyrosine phosphorylated
  • Tir binds IRTKS/IRSp53
  • The EHEC effector EspFu links complex to N-WASP
  • N-WASP stimulates Arp2/3 nucleation of actin
    Pedestal formation
53
Q

What toxin does EHEC produce? What are the 2 immunologically distinct types and how do they differ?

A
  • Shiga-like toxins
  • Stx1, st2
    ○ Stx2 is associated with severe human disease
54
Q

Explain the structure of Shiga-like toxins (EHEC)

A

Ab5 type toxin, active part central with b part surrounding

55
Q

What is the receptors for Shiga-like toxins (EHEC)

A

Gb3

56
Q

Explain the mechanism of action of Stx toxin (EHEC)

A
  • In kidney B subunit of toxin binds to Gb3 which is expressed on cell surface
  • Shiga-like toxin damages blood vessels and kidney cells
  • Action of damage is:
    ○ External toxin enters clathrin coated pit
    ○ Coated vesicle is formed
    ○ Fusion of lysosome with coated vesicle
    ○ Toxin is processed in cytosol
    ○ A1 cleaves 70S ribosomes which inhibits protein
    synthesis
57
Q

What are the major virulence factors of ETEC?

A
  • Adhesion
  • Heat labile toxins (LT)
  • Heat stable toxins (ST)
58
Q

How do ETEC establish adhesion?

A
  • Type 1 Fimbriae
59
Q

Explain the structure and the mechanism of action of Heat labile toxins (LT) (ETEC)

A
  • LT: 2 forms, LT-1 and LT-II
  • Structurally, antigenically and functionally related to cholera toxin
  • Increases Cellular cAMP leading to reduced water absorption (ADP ribosylating toxin)
    ○ AB5 toxin (a peptide in middle, 5 binding peptides surrounding it)
    ○ Attach to host GM1 ganglioside receptor in lipid rafts
    ○ A protein brought closer to host surface and internalized into host cell
    ○ Once inside, A protein breaks into 2 subunits and A1 subunit is activated
    ○ A1 subunit hydrolyses NAD -> A1-ADP-Ribose + Nicotinamide
    ○ A1 uses ADP-ribose to ribosylate Gsa which creates GDP and shifts ATP to cAMP, activating cAMP dependent protein kinase A
    ○ Protein kinase A activates cystic fibrosis transmembreane conductance regulator (CFTR chloride channel) which leads to increased chlorice ion secretion, decreased uptake of NaCl through inhibition and leads to ion imbalence which causes fluid loss due to osmotic pressure
60
Q

Explain the structure and mechanism of action of Heat stable toxins (ST) (ETEC)

A
  • ST structurally distinct from LT
    ○ Small cysteine-rich peptide
    ○ Mimic human signaling peptide
    § Uroguanylin
    § Guanylin
    ○ ST binds to Guanylyl cyclas C receptor located in the apical membrane of host cell
    ○ Guanylyl cyclas regulated intracellular cGMP
    ○ ST leads to increase in cGMP which activates PKG and phosphorylates CFTR leading to loss of fluid
61
Q

What is the difference between toxigenic infection and invasion? (ETEC)

A
  • Toxigenic infection is when bacteria is on the outside of the cell and toxins are used to disrupt normal function
  • Invasion is when bacteria enters cell and destroys it
62
Q

How does EAEC differ from ETEC?

A
  • EAEC does not have LT or ST

- Forms stacked brick formation on cell

63
Q

Explain the pathogenesis of EAEC (5 steps)

A
  • Aggregation of EAEC
  • Adherence to GI epithelium using aggregative adherence fimbriae
  • Stimulation of mucus production and biofilm formation
  • Release of toxins and damage to epithelium
  • Biofilm maturation
64
Q

Explain how EAEC achieves adherence

A
  • Aggregative adherence fimbriaea (AAF)
  • 4 variants which are encoded on large virulence plasmid
  • Interaction between bacteria and cell give stacked brick phenotype
  • Fibronectin, laminin and type 4 collagen proteins used to bind to ECM
  • Dispersin covers cell surface to prevent self-interactions
65
Q

What is the structure, motility and can shigella ferment lactose?

A
  • Gram negative rod
  • Non motile
  • Non fermentation of lactose
66
Q

What is the invasion strategy of shigella?

A
  • Enters M cell and is taken up by a macrophage
  • Kills macrophage (apoptosis) and enters epithelial cells from the sub-mucosal layer
  • Also sends IL-1B to epithelial cells which allow for bacteria to be taken in
67
Q

What are the genes in a shigella flexnerii pathogenicity island?

A
  • Type III secretion system
    ○ Spa - surface presentation of antigen
    ○ Mxi - membrane excretion of invasion plasmid antigen
  • Invasion plasmid antigen (Ipa)
68
Q

How does Shigella Flexnerii invasion work? What are the key proteins and their role?

A
  • When there is contact of shigella to host cell, Mxi-spa apparatus is activated which delivers bacterial invasins (Ipa) into the host cell
  • Multiple genes help with this (in slides)
  • Attachment and entry of Ipa protein leads to extensive cytoskeletal rearrangement
    ○ Pseudopod formation
    ○ Engulfment of shigella (entry into epithelial cell)
    ○ Escape vacuole (IpaB/C) (Multiplication)
69
Q

How does Shigella spread cell to cell?

A

Actin based motility

70
Q

Explain Actin based motility (shigella)

A
  • Production of IcsA which encodes an outer membrane protein
    ○ This protein is localised at pole of bacterium, expression directs actin based motility, deposition of F actin confers a motive force to bacteria which leads to intracellular spread
  • The amount of IcsA on the surface of shigella determines whether tail assembly occurs (lots of IcsA leads to assembly of actin tail and movement)
71
Q

Summarise the intracellular life of shigella

A
  • Bacteria is internalized in primary vacuole
    • Secretion of bacterial escape proteins
    • Disruption of vacuole membrane
    • Actin polymerization and replication
    • Cell protrusion
    • Internalization in secondary vacuole
    • Secretion of bacterial escpae proteins
    • Disruption of - double-membrane vacuole
  • Replication in cytosol
72
Q

What are some challenges faced when dealing with Shigella

A
  • Shigella has multiple drug resistances

- S Flexneri can undergo serotype switching which makes it difficult to combat

BABS3081 (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions