Lectures 1-4 Host Defence in the lung Flashcards
Aetiology Definition
The cause, set of causes, or manner of causation of a disease
Pathogenesis
The origin and development of a disease.
The cellular events and reactions and other pathologic mechanisms occurring in the development of disease.
Name the structures involved in breathing
§ cavities Pharynx (throat) Larynx (voice box) Trachea (windpipe) Bronchi (>3mm) Bronchioles (<3mm) Alveoli (air sacs)
Characteristics of an Obstructive vs. Restrictive condition
Obstructive -
Reduction in air flow
Hard to exhale air (air will remain in lungs after full expiration)
Due to:
Inflammation
Excess mucus
Airway narrowing (smooth muscle tightening)
Restrictive - Reduction in lung volume Hard to inhale air (cannot fully expand lungs) Due to: Lung scarring fibrosis Extra-parenchymal problems
Obstructive conditions - Examples and characteristics
Chronic obstructive pulmonary disease (COPD); Asthma; Bronchitis; etc.
Reduction in air flow
Hard to exhale air (air will remain in lungs after full expiration)
Due to:
Inflammation
Excess mucus
Airway narrowing (smooth muscle tightening)
Restrictive conditions - Examples and characteristics
Interstitial lung disease (ILD); Sarcoidosis; etc.
Reduction in lung volume
Hard to inhale air (cannot fully expand lungs)
Due to:
Lung scarring
fibrosis
Extra-parenchymal problems
What are the classifications of respiratory disease?
Obstructive conditions; restrictive conditions; Infectious, environmental and other disease; vascular disease
Examples of infectious/ environmental disease, Examples of vascular disease
Viral & bacterial infections (Rhinovirus, Tuberculosis, Pneumonia); Asbestosis; Particulate pollutants; etc.
Pulmonary oedema; Pulmonary hypertension; etc.
Environmental factors influencing respiratory disease
11,000 litres air every day
Inhalation exposures - allergens, microbes, aerosolised toxins (tobacco smoke, air pollutants)
Affect vulnerable individuals – spatially (geography), temporally (age), circumstance (comorbid disease, nutrition, economics, race, genetics)
Genetic factors influencing respiratory disease
Monogenic diseases (single gene defects) Polygenic diseases
Gene-environment interactions - lung diseases are not usually single entities
Monogenic diseases - Examples and definition
Rare diseases attributable to genetic variants with large effects
Cystic fibrosis
CFTR
Cl- ion transport
Autosomal recessive
Alpha-1 antitrypsin deficiency
SERPINA1
Serine protease inhibitor
Autosomal recessive
Kartagener’s syndrome (immotile cilia)
DNAI1
Dynein arm, Ciliary function
Autosomal recessive
Hereditary Pulmonary Arterial Hypertension (HPAH)
BMPR2
BMP-signalling, endothelial dysfunction, smooth muscle proliferation
Autosomal dominant
Chronic granulomatous disease
CYBB
Component of phagocyte oxidase complex
Autosomal recessive
Polygenic diseases - examples and definition
Complex disease controlled by two or more genes at different loci on different chromosomes
Asthma
Chronic Obstructive Pulmonary Disease (COPD)
Asthma Genetic Mutations
TLR2, TLR4 ( Pathogen Recognition/ innate immunity),
IL10 (anti-inflammatory), IL4, IL4R (Th2 response, IgE recognition),
IL13 (mucosal production/ IgE production),
IL2R orIL18R (T cell proliferation, Th1 response).
Linkage vs. Association studies?
Linkage studies are performed in families: these are based on the tendency of genetic loci or alleles that are physically close to one another on a chromosome to be inherited together (this is known as genetic linkage).
Association studies begin with the polymorphism or mutation rather than with the disease. They are typically based on a case (people with the disease) –control (healthy subjects) design, in which SNPs are tested for association with a specific phenotype or disease. In single-candidate gene association studies, only one or a few SNPs near or in the gene under study are investigated for association with the disease of interest, based on an a priori hypothesis concerning the possible function and role of the particular gene. In genome-wide association studies, hundreds of thousands of SNPs across the entire human genome are genotyped and tested for association with the phenotype or disease of interest in hundreds or thousands of individuals.
Key points : Innate Immune system
First line of defence, remains unchanged from birth, evolutionarily conserved, recognition of invading pathogens and activation of antimicrobial response. The innate immune system is also implicated in the development of some human disease and is emerging as a critical regulator of human inflammatory disease
