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3s2: Infection and Immunity > Week 9 > Flashcards

Week 9 Flashcards

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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
What are the main ways for staphylococcus aures death?
Top 3: Pneumonia, bloodstream and intra-abdominal
25
What is an overview of the virulence factor coagulase?
Stimulates blood clotting
26
What is an overview of blood clotting?
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
27
What is an overview of the properties of fibrin fibres?
Fibrin polymers are viscous like honey Greater extensibility than spider silk Fibrin fibers make up the protein mesh that makes blood clots strong
28
How is thrombin activated?
Exists as inactive prothrombin Proteolytic cleavage of prothrombin by cleaving extra domain off allowing it to bind to activation site
29
How does coagulase function?
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
30
What is an overview of a major clinical test to identify Staphylococcus species?
Coagulase test Place solution of glass slide or tube and if coagulase is present clots form Ie differentiating between Staphylococcus epidermis and S. aureus
31
What is an overview of alpha-toxin?
Pore-forming toxin Apart of the haemolysin family Binds to membrane and inserts
32
What is an overview of alpha-toxin mechanism?
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
What is an overview of alpha-toxin function?
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
What are mechanisms that Staphylococcus aureus can use to evade innate immune system?
SEIW – staphylococcal superantigen SEIX – staphylococcal enterotoxin-like toxin X (inhibits phagocytosis) Eap – Extracellular adhesin protein Nuc – staphylococcal nuclease (prevents netosis)
35
What are neutrophil extracellular traps?
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
How does NETs occur?
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
How can Staphylococcus aureus circumvent adaptive immuntiy?
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
What is an overview of Streptococcus pneumoniae?
Gram positive, non motile, non spore forming diplococcoid bacterium, alpha haemolytic, competent (takes up DNA) Phylum: Firmicutes Order: Lactobacillales Family: Streptococcaceae
39
Where is Streptococcus pneumoniae commonaly found?
Commonly found: Upper respiratory tract (nose, 20-40% of humans), skin, throat, intestine
40
What is an overview of asymptomatic coloniser of respiratory tract and nasal cavity?
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
What makes up Streptococcus pneumoniae deaths?
Mostly pneumonia but of bloodstream and meningitis
42
What are virulence factors for colonisation of Streptococcus pneumoniae?
Ply – pneumococcal lysin (pore forming) Pilus – adherence with epithelia Cell wall – anchor for surface proteins Capsule – immune evasion
43
What is an overview of Streptococcus pneumoniae vaccines?
There are currently 4 conjugate vaccines that cover up to 23 capsular types of S. pneumoniae
44
What is an overview of Streptococcus pneumoniae cell wall?
Polysaccharide that is made in cell then exported and attached Interferes with host defences Protects cells from opsonization Strengthens cells from environmental stress
45
What is an overview of Lancefield streptococci
Rebecca Lancefield identified Human pathogenic: group A streptococci ‘strep throat’ and Bovine pathogenic: group B streptococci
46
What is an overview of Streptococcus agalactiae?
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
Where is Streptococcus agalactiae found?
Commonly found: humans, milk, cows, fish, raw seafood Asymptomatic coloniser of genitourinary tract and gastrointestinal tract
48
What is an overview of Streptococcus agalactiae genitourinary tract and gastrointestinal tract infection?
25% of adult women, 10% of male adults are carriers Vertical transmission from mother to baby occurs during birth
49
What are the impacts of Streptococcus agalactiae genitourinary tract and gastrointestinal tract infection?
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
What are the impacts of in utero Streptococcus agalactiae infection?
Fatal demise Still birth Early-onset sepsis
51
What are the impacts of perinatal Streptococcus agalactiae infection?
Early-onset sepsis Neonate colonized Lead to late-onset
52
What are the impacts of postnatal Streptococcus agalactiae infection?
Asymptomatic colonization Risk of late-onset disease
53
What areas are most at risk regions of Streptococcus agalactiae?
UK South Africa USA Also the best countries at recognising it so skewed
54
What are the burdens of Streptococcus agalactiae?
Healthcare burden Agriculture burden Aquaculture burden
55
What are the main deaths for Streptococcus agalactiae?
Main ones are pneumonia and bloodstream infections
56
What is an overview of Streptococcus agalactiae non-protein cyto-toxin?
Rhamnolipid - granadaene Not fully known how but believed to be a pore forming molecule
57
What is an overview of Enterococcus faecalis?
Gram positive, non motile, non spore forming, facultative anaerobe, ovoid bacterium Phylum: Firmicutes Order: Bacillales Family: Enterococcaceae
58
Where is Enterococcus faecalis found?
Commonly found: GI tract, urinary tract, catheter associate Frequent colonizer of the GI and urinary tract, highly adaptable
59
What is an overview of Enterococcus faecalis pathogen?
Difficult to treat, requires intravenous multi-antibiotic approach Also causes wound infections (surgery), bacteremia and sepsis, endocarditis, peritonitis
60
What is an overview of Enterococcus faecalis infection?
Establishes strong biofilms, often with other microbes (polymicrobial) Multi-drug resistance, including Vancomycin-resistant Enterococcus (VRE)
61
What is an overview of Enterococcus faecalis vs Enterococcus faecium?
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
How can Enterococcus faecalis prevent disease outbreak in host?
Produces antibacterial molecules which inhibit Streptoccocus mutants from forming biofilms Produces anti fungal molecule which inhibit Candida albicans from forming biofilms
63
How can Enterococcus faecalis increase disease outbreak in host?
Promote joint biofilm with S. aureus and E. coli S. aureus can get VAN A gene from these biofilms to circumnavigate antibiotics
64
What are the main Enterococcus faecalis and Enterococcus faecium deaths?
Peritoneal and intra-abdomina and bloodstream
65
What is an overview of Streptococcus pyogenes?
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
Where is Streptococcus pyogenes commonaly found?
Commonly found: skin, throat
67
What is an overview of Streptococcus pyogenes infection?
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
What is an overview of invasive Streptococcus pyogenes infection?
Invasive: Bacteremia, cellulitis, puerperal sepsis, necrotizing fasciitis, streptococcal toxic shock syndrome
69
What are major Streptococcus pyogenes virulence factors?
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
What are antibiotics that Streptococcus pyogenes resist?
Macrolides Tetracyclines Fluoroquinolones B-lactams Sulfamethoxazole
71
What is an overview of Streptococcus pyogenes vaccines?
NO vaccines available, yet Most dont fail before making it to phase 2
72
What is an overview of Streptococcus pyogenes deaths?
Vast majority are skin infections next biggest being bloodstream deaths
73
What is an overview of Streptococcus in news?
Increased in schools Large increase in scarlet fever but 30 died in 2 months at end of 2022 though small subpopulation
74
What is an overview of Clostridioides difficile?
Obligate anaerobe (only grows in the absence of oxygen), urgent threat due to antimicrobial resistance. Lives in the intestines and colon
75
What is an overview of Clostridioides difficile infection?
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
What are examples of other notable gram-negative pathogens?
Listeria monocytogenes Chlamydia species Other staphylococci – S. epidermidis, S. haemolyticus (Coagulase-negative Staphylococcus (CoNS) Other streptococci – S. mutans, S. mitis
77
What are urgent threat Gram postive bacteria?
Clostridiodes difficule
78
What are serious threat Gram postive bacteria?
Vancomycin-resistant enterococci Methicillin-resistant Staphyloccus aureus
79

3s2: Infection and Immunity (12 decks)

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