Bacterial infections

Question 1

innate immune reponse to bacterial infections

Answer 1

EXTRACELLULAR BACTERIA:
- complement activation -> alternative or lectin pathway, opsonisation, phagocytosis and lysis, inflammation and leukocyte activation
- phagocytosis -> direct or indirect recognition, degradation is oxygen dependent or independent

INTRACELLULAR BACTERIA:
- neutrophils and macrophages, NK cell activation
- e.g. Salmonella: LPS and lipopeptide over TLR4/2, Flagellin over TLR5 and NLRC4, MyD88 mediated signalling, macrophage recruitment but salmonella replication in SCV

Question 2

Adaptive immune response to bacterial infections

Answer 2

INTRACELLULAR BACTERIA:
- Ab are inefficient
- TH1 release IFNg to activate macrophages
- TH17 secrete IL17 to recrut neutrophils
- CTLs kill directly

in chronic infections pathogens can be contained by T and B cells in granuloma

Question 3

Bacterial virulence factors

Answer 3

surface proteins
extracellular products
morphological changes
assortment (biofilm formation)

Question 4

Surface virulence factors
Staphylococcus aureus

Answer 4

Surface:
- SpA: binds Fc of Ab, or binds/masks Fab region as superantigen causing B cell apoptosis
- ClfA: clumping factor binds fibrinogen, internalization via integrin -> adhesion and intracellular relocation
- FnBP: fibronectin, internalization via intergin -> adhesion and intracellular relocation
- Capsule: inhibits phagocytosis

Question 5

extracellular virulence factors
Staphylococcus aureus

Answer 5

• direct tocins: haemolysins, enterotoxins (e.g. PVL causing detsruction, necrosis and inflammation)
• immunological active components: TSST-1 causing toxic shock syndrome
• coagulase or staphylokinase: influence adhesion or invasion

Question 6

Virulence factors Staphylococcus aureus

Answer 6

• Surface: SpA, ClfA, FnBP, capsule
• extracellular products: toxins, immunological active (TSST-1), adhesion & invaion (coagulase)
• morphological changes -> SCV
• Biofilm formation

Question 7

VIrulence factors Staphylococcus epidermidis

Answer 7

• Biofilm formation
• PGA: inhibits phagocytosis
• PSM: lysis of white and red blood cells
• Enterotoxins, lipases and proteases

Question 8

PGA

Answer 8

virulence factor staphylococcus epidermidis
inhibits phagocytosis

Question 9

PSM

Answer 9

virulence factor Staphylococcs epiermidis
lysis of white and red blood cells

Question 10

SpA

Answer 10

protein A
Surface virulence factor Staphylococcus aureus

binds Fc of Ab, or binds/masks Fab region as superantigen causing B cell apoptosis

Question 11

ClfA

Answer 11

Clumping factor A
Surface virulence factor Staphylococcus aureus

clumping factor binds fibrinogen, internalization via integrin -> adhesion and intracellular relocation

Question 12

FnBP

Answer 12

fibronectin-binding protein
Surface virulence factor Staphylococcus aureus

internalization via intergin -> adhesion and intracellular relocation

Question 13

Virulence factors Escherichia coli

Answer 13

many different types with different virulence factors

enteroinvasive, enteropathogenic, enterotoxigenic, enteroagregative, uropathogenic and enterohaemoragic

EHEC: adherance via intimin -> destruction of microvilli
EHEC (& STEC) produce Shiga toxin -> splits rRNA
- causes HUS and complement activation
- leads to damage of endothel, especially in renal capillaries
- uremia and renal failure
- haemolysis, haemolytic anemia dn thrombopenia due to complement activation

Question 14

MIC

Answer 14

minimal inhibitory concnetration
prevents growth for 24h in nutrient solution

Question 15

MBC

Answer 15

minimal bactericidal concentration
reduces number of viable bacteria in 24 hors by 3 tenth powers

Question 16

clinical resistance

Answer 16

MIC is higher than clinical applicable dose

Question 17

Resistance (scientific)

Answer 17

bining of drug to target is prevented by e.g. modifications

Question 18

Tolerance

Answer 18

MBC more than 32x MIC (usually 2-4x)
bindig of drug to target is possibel but additional changes reduce efficacy
tolerant bacteria are “persisters”

Question 19

Persisters
definition and elimination

Answer 19

“persisters” -> susceptible but MBC is unapplicable due to tolerance (MBC > 32x MIC)
can loose tolerant phenoytpe in therapy-free interval due to loss of selective pressure

Elimination: therapy-free intervals to increase susceptibility, finding time interval is individual and difficult

Question 20

post-antibiotic or post-antiseptic effect

Answer 20

delayed growth after removal of AB after application of sub-lethal doses
leads to a REFRACTORY PERIOD in which application of AB has no effect!
important to time AB adminstration intervals