BB5MOP - Week 19

What causes CF?

Autosomal recessive disorder inherited from parents.

Where is the CFTR protein found and what does CFTR do?

1. Found in lining of the airways of the lungs.

2. Regulates Cl- movement, affecting water movement and cilia beating.

What is the consequence of a malfunctioned CFTR protein?

1. Less Cl- movement, so less water in the airway surface fluid (ASF).

2. Thicky sticky mucus interferes with cilia beating, difficult to clear bacteria so easy to cause infection.

What are Toll-like receptors (TLRs)?

Recognise pathogen-associated-molecular patterns (PAMPs).

What are antimicrobial peptides?

Natural antibiotics produced by the body.

What does secretory IgA do?

Prevent bacteria from attaching to the cell lining.

What happens to TLRs in CF airways?

1. TLR is altered, increasing TLR2 recognizing gram positive bacteria, increased inflammation.

2. Decrease in TLR4, less able to detect bacteria and affect molecules that regulate inflammation.

What happens to antimicrobial peptides in CF airways?

Less effective, lysozymes become less effective.

What happens to secretory IgA in CF airways?

Reduced and broken down by enzymes.

What happens in CF airways, in relation to neutrophils?

1. Neutrophils are in high numbers, cannot do their function.

2. Cannot do chlorination, mucus traps neutrophils preventing movement.

3. Release of neutrophil elastase attacking complement proteins instead of pathogen.

What happens to macrophages in CF airways?

Less effective at phagocytosis, issues with TLR4 and MHC Class 2 presentation.

What do CF macrophages release?

Release pro-inflammatory molecules contributing to chronic inflammation in lungs.

What does P. aeruginosa isolation agar (PIA) enhance the production of?

Production of pyocyanin.

What are the virulence mechanisms that P. aeruginosa uses?

1. Flagella

2. Modifying LPS

3. Siderophores

4. Pyocyanin

5. Elastase B

6. Biofilm

Describe the mechanism of flagella in P. aeruginosa infection.

Binding to mucin MUC1, activating TLR5, but pathogen evolved to evade TLR5 activation.

Describe the mechanism of modifying LPS in P. aeruginosa infection.

Pathogen can modify its own LPS.

Describe the mechanism of siderophores in P. aeruginosa infection.

Compete for ions which are needed for bacterial growth.

Describe the mechanism of pyocyanin in P. aeruginosa infection.

Inhibits cilia from beating and induces neutrophil apoptosis and function.

Describe the mechanism of elastase B in P. aeruginosa infection.

Degreades lysozymes and complement components.

Describe the mechanism of biofilm in P. aeruginosa infection.

Forms biofilm encased in matrix to protect it from immune cells.