29 Questions
What is the primary cause of cystic fibrosis?
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
What role does the CFTR protein play in the body?
Regulating chloride and water transport across cell membranes
What is the consequence of the misfolded CFTRΔF508 protein being retained in the endoplasmic reticulum (ER)?
Dysfunctional chloride and water transport
What effect does altered ion transport due to dysfunctional CFTR protein have on airway surface?
Dehydration of the airway surface, leading to production of thick and sticky mucus
What is the role of neutrophils in the immune response?
Neutrophils are crucial in the immune response, particularly against bacterial infections
What leads to impaired ion transport and mucus accumulation in cystic fibrosis (CF)?
Dysfunctional CFTR gene
What is a consequence of sustained inflammatory response in CF?
Recruitment of neutrophils to affected sites
What do activated neutrophils release to combat pathogens?
Reactive oxygen species (ROS), proteases, and toxic granule contents
What do toxic granule contents released by activated neutrophils cause?
Direct damage to host tissues, including the epithelial lining of the airways
What contributes to a remodeling process in the airways in CF?
Chronic and repetitive cycles of inflammation and tissue damage
What is the gold standard for diagnosing cystic fibrosis?
Sweat chloride test
Which test is relevant for monitoring CF patients but not directly used for diagnosing CF?
White blood cell count
Which therapeutic approach aims to address the underlying genetic defect in CF?
$CFTR$ modulators like Ivacaftor
What contributes to the resolution of acute P. aeruginosa infection in cystic fibrosis?
$TLR$ signaling
What is a common feature of blood tests in cystic fibrosis due to chronic respiratory infections?
$Neutrophil$ increase
Which therapeutic approach aids in digestion and nutrient absorption for CF patients with pancreatic insufficiency?
$Enzyme replacement therapy with pancreatic enzymes$
What is the role of neutrophils in clearing P. aeruginosa infection?
Contribute to resolution of infection through phagocytosis and antimicrobial mechanisms
What do pro-inflammatory cytokines contribute to in response to P. aeruginosa infection?
Inflammatory response and activation of immune cells for defense
What are therapeutic approaches for managing symptoms, preventing complications, and improving overall quality of life for CF patients aimed at?
Achieving better quality of life despite no cure for CF
What is used as part of airway clearance techniques for CF patients?
Airway clearance techniques
What is the most common CF-causing mutation?
Deletion of a single amino acid at position 508 in the CFTR protein
What contributes to chronic inflammation in the airways of CF patients?
Continuous recruitment of immune cells and chronic infections
What is the consequence of impaired mucociliary clearance in CF?
Accumulation of mucus and pathogens, creating an ideal environment for bacterial colonization
What is the impact of the misfolded CFTRΔF508 protein on cellular function?
Induces stress on the endoplasmic reticulum, contributing to cellular dysfunction
Which cytokines are commonly elevated in the airways of individuals with CF?
$IL-6$, $IL-8$, and $TNF-α$
What do elevated cytokine levels often correlate with in individuals with CF?
$Severity$ of lung disease
What role do neutrophils and macrophages play in the airways of CF patients?
Release inflammatory cytokines such as IL-6
What is the consequence of abnormal ion transport across cell membranes due to mutated CFTR protein?
Disrupts normal hydration of mucus
What triggers an immune response in the airways of individuals with CF?
The presence of microbes
Study Notes
Inflammation and Immune Response in Cystic Fibrosis
- Cystic fibrosis (CF) is primarily caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to impaired chloride and water transport across cell membranes.
- The most common CF-causing mutation is the deletion of a single amino acid at position 508 in the CFTR protein (CFTRΔF508), resulting in defective CFTR protein synthesis and ion imbalance in various organs.
- Impaired mucociliary clearance in CF allows mucus and pathogens to accumulate, creating an ideal environment for bacterial colonization, particularly by opportunistic pathogens like Pseudomonas aeruginosa.
- CF patients are also susceptible to fungal infections, further contributing to airway inflammation.
- The presence of microbes triggers an immune response, leading to the recruitment of neutrophils and macrophages to the airways, releasing inflammatory cytokines such as IL-6.
- Chronic infections and continuous recruitment of immune cells contribute to chronic inflammation in the airways, leading to tissue damage and remodeling.
- The misfolded CFTRΔF508 protein induces stress on the endoplasmic reticulum, contributing to cellular dysfunction, and affects calcium homeostasis in epithelial cells, potentially contributing to inflammation.
- The mutated CFTR protein, especially CFTRΔF508, leads to impaired chloride secretion and abnormal ion transport across cell membranes, disrupting the normal hydration of mucus and leading to the production of thick and sticky mucus in various organs.
- The abnormal mucus in the airways becomes a breeding ground for bacteria and other pathogens, triggering an inflammatory response involving the release of cytokines and other immune signaling molecules.
- Pro-inflammatory cytokines, such as IL-6, IL-8, and TNF-α, are commonly elevated in the airways of individuals with CF, contributing to chronic inflammation and airway obstruction.
- Elevated cytokine levels, especially IL-6 and IL-8, often correlate with the severity of lung disease in CF and are associated with acute exacerbations.
- Cytokine levels, particularly in bronchoalveolar lavage fluid or sputum samples, are sometimes used as biomarkers to assess disease activity and response to treatment, leading to the exploration of anti-inflammatory strategies as potential therapeutic interventions.
Learn about the role of neutrophils in the immune response and how their dysregulated activity contributes to tissue damage and remodeling in cystic fibrosis.
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