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3s2: Infection and Immunity > Week 9 > Flashcards

Week 9 Flashcards

1
Q

What are the process required for disease?

A

Gain access to the host - contamination
Adhere to the host - adherence
Replicate on the host - colonization
Invade tissues - invasion
And produce toxins, proteins or other agents that cause host harm - damage

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2
Q

What are types of skin infections?

A

Dermatitis
Necrotizing fasciitis

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3
Q

What are types of eye infections?

A

Conjunctiva - conjunctivitis
Eye lids - blepharitis
Cornea - keratitis

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4
Q

What are types of ear and upper respiratory infections?

A

Ears - Otitis media
Upper respiratory - rhinosinusitis pharyngitis, diptheria

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5
Q

What are types of lower respiratory infections?

A

Pneumonia Tuberculosis, pertussis Legionnaires disease

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6
Q

What are types of urogenital and reproductive tract infections?

A

Cystitis, pyelonephritis, glomerulonephritis

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6
Q

What are types of digestive tract and oral cavity infections?

A

Digestive tract - gastroenteritis diarrheal disease
Oral cavity - gingivitus

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7
Q

What are types of circulatory infections?

A

Sepsis toxic shock syndrome, endocarditis, pericarditis, rheumatic fever, infectious arthritis

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8
Q

What are types of nervous infections?

A

Meningitis, tetanus, botulism

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9
Q

What are the two major gram-positive genera?

A

Staphylococcus
Streptococcus

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10
Q

How can you differentiate between the two staphylococcus?

A

Coagulase
Coagulase postive - Staphylococcus aureus
Coagulase negative - Other staphylococci eg Staphylococcus epidermidis and S. capitis

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11
Q

What is an overview of Staphylococcus aureus?

A

Golden staph
Hemolytic
Causes clots (fibrin)
Serious invasive disease E.g. staphylococcal toxic shock

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12
Q

What is an overview of other staphylococcus?

A

Harmless when outside of body
Does not have coagulase enzyme

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13
Q

What is the difference between alpha, beta and gamma heolysis?

A

alpha-hemolytic streptococcal colonies are surrounded by a small zone of hemolysis
Beta-hemolyticstreptococci show a larger well defined clear zone of hemolysis around the colony
Gamma-hemolytic streptococci have no effect on the red blood cells

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14
Q

What are examples of alpha hemolytic steptococcus?

A

Streptococcus pneumoniae

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15
Q

What are examples of gamma hemolytic steptococcus?

A

Enterococcus faecalis
Enterococcus faecium

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16
Q

What are examples of beta hemolytic steptococcus?

A

Streptococcus pyogenes,
Streptococcus Agalactiae

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17
Q

What is an global burden of human gram postive bacterial infections?

A

Staphylococcus aureus 1,105,000 deaths
Streptococcus pneumoniae 829,000 deaths
Streptococcus agalactiae 320,000 deaths
Enterococcus faecalis 220,000 deaths
Enterococcus faecium 219,000 deaths
Streptococcus pyogenes 198,000 deaths

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18
Q

What is an overview of Staphylococcus aures?

A

Gram positive, non motile, coagulase positive, catalase positive coccoid bacterium
Phylum: Firmicutes
Order: Bacillales
Family: Staphylococcaceae

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19
Q

Where is Staphylococcus aures found?

A

Commonly found: Upper respiratory tract (nose, 20-40% of humans), skin, throat, intestine

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20
Q

How severe is Staphylococcus aures antibiotic resistance?

A

Serious threat for antimicrobial resistance (CDC, USA)
Methicillin resistant Staphylococcus aureus (MRSA)

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21
Q

What is an overview of mild staphylococcus aures infection?

A

Mild skin and soft tissue infections, ear (otitis)

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22
Q

What is an overview of severe staphylococcus aures infection?

A

Lower respiratory infections,
Bacteremia and septicaemia
Staphylococcal toxic shock syndrome
Osteomyelitis and septic arthritis
Pneumonia and endocarditis

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23
Q

What is an overview of the pathogenic potential of staphylococcus aures?

A

Acute, recurrent, chronic or persistent disease
Large array of virulence factors & immune evasion factors
Evades adaptive immune responses; no protective immune
responses, recurrent infection,
No vaccines currently available

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24
Q

What are the main ways for staphylococcus aures death?

A

Top 3: Pneumonia, bloodstream and intra-abdominal

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25
Q

What is an overview of the virulence factor coagulase?

A

Stimulates blood clotting

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26
Q

What is an overview of blood clotting?

A

Fibrinogen
Thrombin is the enzyme that cleaves fibrinogen to form fibrin polymers
Fibrin readily polymerises to make fibrin polymers
Factor XIIIa covalently links the mesh together

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27
Q

What is an overview of the properties of fibrin fibres?

A

Fibrin polymers are viscous like honey
Greater extensibility than spider silk
Fibrin fibers make up the protein mesh that makes blood clots strong

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28
Q

How is thrombin activated?

A

Exists as inactive prothrombin
Proteolytic cleavage of prothrombin by cleaving extra domain off allowing it to bind to activation site

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29
Q

How does coagulase function?

A

Staph coagulase has a domain which mimics the self activation domain
Activating Staphylothrombin induced clotting
Makes microenviroment surrounded by fibrin-based psudocapsule protecting from threats such as immune cells and certain antibiotics

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30
Q

What is an overview of a major clinical test to identify Staphylococcus species?

A

Coagulase test
Place solution of glass slide or tube and if coagulase is present clots form
Ie differentiating between Staphylococcus epidermis and S. aureus

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31
Q

What is an overview of alpha-toxin?

A

Pore-forming toxin
Apart of the haemolysin family
Binds to membrane and inserts

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32
Q

What is an overview of alpha-toxin mechanism?

A

S. Aureus secretes α-toxin
Binds to ADAM10 receptor on erythrocytes
This forms a partial pore
Oligomerisation of partial pores making pore structure with 7 of them needed

33
Q

What is an overview of alpha-toxin function?

A

Enables destruction of the host membrane
Allows scavenging of cytosolic contents by S. aureus
S. aureus has multiple PFTs that target different receptors on different cell- types

34
Q

What are mechanisms that Staphylococcus aureus can use to evade innate immune system?

A

SEIW – staphylococcal superantigen
SEIX – staphylococcal enterotoxin-like toxin X (inhibits phagocytosis)
Eap – Extracellular adhesin protein
Nuc – staphylococcal nuclease (prevents netosis)

35
Q

What are neutrophil extracellular traps?

A

Protein and DNA matrices
Expelled from dying / activated neutrophils during NETosis
Very sticky substance, captures pathogens and aids in removal
Promoted by certain inflammatory signals like IL

36
Q

How does NETs occur?

A

Emits nuclease chopping up DNA destablising extracellular net
Using chopped up DNA and ATP, adenosine synthase, chops off phosphate drops from ATP, ADP and AMP producing deoxyadenosine, which triggers apoptosis

37
Q

How can Staphylococcus aureus circumvent adaptive immuntiy?

A

Secrete SplB and Aurovision to nullfiy complement proteins by degradation
Sbi – staphylococcal immunoglobulinbinding protein via Fc region of IgGs with high affinity via two surface exposed globular domains allow it to resist opsonophagocytosis

38
Q

What is an overview of Streptococcus pneumoniae?

A

Gram positive, non motile, non spore forming diplococcoid bacterium, alpha haemolytic, competent (takes up DNA)
Phylum: Firmicutes
Order: Lactobacillales
Family: Streptococcaceae

39
Q

Where is Streptococcus pneumoniae commonaly found?

A

Commonly found: Upper respiratory tract (nose, 20-40% of humans), skin, throat, intestine

40
Q

What is an overview of asymptomatic coloniser of respiratory tract and nasal cavity?

A

27-65% of children, 10% of adults are carriers
Primary cause of community acquired pneumonia
Also causes bronchitis, rhinitis, acute sinusitis, otitis
media, conjunctivitis
Meningitis, sepsis, osteomyelitis, septic arthritis, brain abscesses, endocarditis, peritonitis, pericarditis, cellulitis
100 different serotypes, large array of virulence factors

41
Q

What makes up Streptococcus pneumoniae deaths?

A

Mostly pneumonia but of bloodstream and meningitis

42
Q

What are virulence factors for colonisation of Streptococcus pneumoniae?

A

Ply – pneumococcal lysin (pore forming)
Pilus – adherence with epithelia
Cell wall – anchor for surface proteins
Capsule – immune evasion

43
Q

What is an overview of Streptococcus pneumoniae vaccines?

A

There are currently 4 conjugate vaccines that cover up to 23 capsular types of S. pneumoniae

44
Q

What is an overview of Streptococcus pneumoniae cell wall?

A

Polysaccharide that is made in cell then exported and attached
Interferes with host defences
Protects cells from opsonization
Strengthens cells from environmental stress

45
Q

What is an overview of Lancefield streptococci

A

Rebecca Lancefield identified Human pathogenic: group A streptococci ‘strep throat’ and Bovine pathogenic: group B streptococci

46
Q

What is an overview of Streptococcus agalactiae?

A

Gram positive, non motile, non spore forming streptococcal bacterium, beta haemolytic, commensal and opportunistic pathogen
Phylum: Firmicutes
Order: Lactobacillales
Family: Streptococcaceae
Group B Step

47
Q

Where is Streptococcus agalactiae found?

A

Commonly found: humans, milk, cows, fish, raw seafood
Asymptomatic coloniser of genitourinary tract and gastrointestinal tract

48
Q

What is an overview of Streptococcus agalactiae genitourinary tract and gastrointestinal tract infection?

A

25% of adult women, 10% of male adults are carriers
Vertical transmission from mother to baby occurs during birth

49
Q

What are the impacts of Streptococcus agalactiae genitourinary tract and gastrointestinal tract infection?

A

Primary cause of often fatal neonatal infections, such as meningitis, sepsis, pneumonia in infants < 3 months old
One of the leading cause of death and morbidity in newborn infants
Elderly and immunocompromised at risk from invasive disease
10 different serotypes, large array of virulence factors

50
Q

What are the impacts of in utero Streptococcus agalactiae infection?

A

Fatal demise
Still birth
Early-onset sepsis

51
Q

What are the impacts of perinatal Streptococcus agalactiae infection?

A

Early-onset sepsis
Neonate colonized
Lead to late-onset

52
Q

What are the impacts of postnatal Streptococcus agalactiae infection?

A

Asymptomatic colonization
Risk of late-onset disease

53
Q

What areas are most at risk regions of Streptococcus agalactiae?

A

UK
South Africa
USA
Also the best countries at recognising it so skewed

54
Q

What are the burdens of Streptococcus agalactiae?

A

Healthcare burden
Agriculture burden
Aquaculture burden

55
Q

What are the main deaths for Streptococcus agalactiae?

A

Main ones are pneumonia and bloodstream infections

56
Q

What is an overview of Streptococcus agalactiae non-protein cyto-toxin?

A

Rhamnolipid - granadaene
Not fully known how but believed to be a pore forming molecule

57
Q

What is an overview of Enterococcus faecalis?

A

Gram positive, non motile, non spore forming, facultative anaerobe, ovoid bacterium
Phylum: Firmicutes
Order: Bacillales
Family: Enterococcaceae

58
Q

Where is Enterococcus faecalis found?

A

Commonly found: GI tract, urinary tract, catheter associate
Frequent colonizer of the GI and urinary tract, highly adaptable

59
Q

What is an overview of Enterococcus faecalis pathogen?

A

Difficult to treat, requires intravenous multi-antibiotic
approach
Also causes wound infections (surgery), bacteremia and sepsis, endocarditis, peritonitis

60
Q

What is an overview of Enterococcus faecalis infection?

A

Establishes strong biofilms, often with other microbes (polymicrobial)
Multi-drug resistance, including Vancomycin-resistant Enterococcus (VRE)

61
Q

What is an overview of Enterococcus faecalis vs Enterococcus faecium?

A

Some factors are shared eg EsP, eDNA and Atla
E. faecalis well studied with numerous factors involved in complex biofilm formation
E. faecium less well studied, only a number of known factors involved
Despite differences, both cause similar numbers of cases/deaths

62
Q

How can Enterococcus faecalis prevent disease outbreak in host?

A

Produces antibacterial molecules which inhibit Streptoccocus mutants from forming biofilms
Produces anti fungal molecule which inhibit Candida albicans from forming biofilms

63
Q

How can Enterococcus faecalis increase disease outbreak in host?

A

Promote joint biofilm with S. aureus and E. coli
S. aureus can get VAN A gene from these biofilms to circumnavigate antibiotics

64
Q

What are the main Enterococcus faecalis and Enterococcus faecium deaths?

A

Peritoneal and intra-abdomina and bloodstream

65
Q

What is an overview of Streptococcus pyogenes?

A

Gram positive, non motile, non spore forming, aerotolerant, coccoid bacterium
Group A strep
Phylum: Bacillota (synonym Firmicutes)
Order: Bacillales
Family: Enterococcaceae
Often why people take strepsils

66
Q

Where is Streptococcus pyogenes commonaly found?

A

Commonly found: skin, throat

67
Q

What is an overview of Streptococcus pyogenes infection?

A

Superficial: Pharyngitis, Scarlet Fever, Impetigo
Sequelae: Rhuematic fever, rheumatic heart
disease, post-streptococcal glomerulonephritis
Other associated: otitis media, sinusitis, meningitis, endocarditis, pneumonia, peritonitis, osteomyelitis

68
Q

What is an overview of invasive Streptococcus pyogenes infection?

A

Invasive: Bacteremia, cellulitis, puerperal sepsis, necrotizing fasciitis, streptococcal toxic shock syndrome

69
Q

What are major Streptococcus pyogenes virulence factors?

A

M protein and capsule facilitate adhesion to epithelia
Streptococcal pyrogenic exotoxin B (SpeB) induce epithelial cell death for invasion of deeper underlying tissue
S. pyogenes eludes these mechanisms by e.g. disrupting Neutrophil extracellular traps (NETs)
Secretes enzymes to degrade IgG

70
Q

What are antibiotics that Streptococcus pyogenes resist?

A

Macrolides
Tetracyclines
Fluoroquinolones
B-lactams
Sulfamethoxazole

71
Q

What is an overview of Streptococcus pyogenes vaccines?

A

NO vaccines available, yet
Most dont fail before making it to phase 2

72
Q

What is an overview of Streptococcus pyogenes deaths?

A

Vast majority are skin infections next biggest being bloodstream deaths

73
Q

What is an overview of Streptococcus in news?

A

Increased in schools
Large increase in scarlet fever but 30 died in 2 months at end of 2022 though small subpopulation

74
Q

What is an overview of Clostridioides difficile?

A

Obligate anaerobe (only grows in the absence of oxygen), urgent threat due to antimicrobial resistance. Lives in the intestines and colon

75
Q

What is an overview of Clostridioides difficile infection?

A

Usually takes hold in patients already taking antibiotic treatment for something else (nosocomial pathogen)
Causes life-threatening diarrhea in weakened and immunocompromised patients
Difficult to treat due to resistance mechanisms
Significant healthcare burden

76
Q

What are examples of other notable gram-negative pathogens?

A

Listeria monocytogenes
Chlamydia species
Other staphylococci – S. epidermidis, S. haemolyticus (Coagulase-negative Staphylococcus (CoNS)
Other streptococci – S. mutans, S. mitis

77
Q

What are urgent threat Gram postive bacteria?

A

Clostridiodes difficule

78
Q

What are serious threat Gram postive bacteria?

A

Vancomycin-resistant enterococci
Methicillin-resistant Staphyloccus aureus

79
Q
A

3s2: Infection and Immunity (12 decks)

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