What is the purpose of the respiratory system?
- Transfer O2 from the environment to RBC’s
- Transfer CO2 from the blood to the air
- Regulate acid-base balance
Describe the bronchial system:
Bronchioles divide 22 in total.
What are the characteristics asthma?
- variable air flow obstruction
- inflammation and remodelling
- hyperresponsive
- thickening of basement membrane (airway wall remodelling)
- inflammatory cell infiltrate permeates the sub mucus a generates the airway wall remodelling leading to airflow obstruction:
- reduced airflow on expiration
- reduced FEV1 to <80%.
- measured in spirometry
- Occlusion of the airway by airway mucus
How id asthma tested for?
Breath in salt water and cough out sputum
What occurs when allergic (allergic and non-allergic aviation pathway)?
- Eosinophilic inflammation induced by allergen species and non-allergen-specific pathways.
- Allergens picked up by dendritic cells, presented to naïve T cells in airway submucosa where they’re presented to a T cell and stimulates B-cells which provide IGE and call mast cells
- Mast Cells: can then create a production of mucus and draw eosinophils to the airway.
What is the role of IgE?
- Mast cells bind IgE
- IgE –> lowest serum concentration of all antibodies
- Dominantly tissue bound to F(CE)R1 on mast cells and basophils.
- F(CE)R1 receptor density strongly correlated with F2-4, IgE.
What are some asthma triggers?
- Air pollution
- Allergens
- Exercise
- Viral infections: responsible for 78% of asthma addmissions to hosptials in chidlren, 70% in adults (flu most common).
- Cigarettes
- asthma thunderstrom
Impact of pollen in causing asthma:
- contains male gametes and consists of showering plants
- plants use either the wind or animals (or both) to carry pollen between individuals
- a fine powdery substance produced by plants in their process of sexual reproduction.
- contains the gametes, pollen itself isn’t the gametes.
- grasses are wind pollinated
How do you count pollen?
- Machine collects pollen in through a vacuum at the same rate humans breath
- sticky slide collects the pollen grains.
- pollen grains are stained and counted.
What is thunderstorm asthma?
- 10th wettest spring on record.
- Causes:
- high levels of grass pollen
- dusty thunderstorms - causes fragmentation of pollen molecules as they can be respired.
Do mast cells and histamine die?
No, release over a peroid of time, resynthesise their mediators and re-package them into granules.
What is the role of IgE in the response to allergens?
- IgE can bind to the high-affinity F(CE)R1 receptor on mast cells waiting to encounter allergens sensitive to them.
Why do we have mast cells?
Protective role:
1. certain bacteria
2. certain viruses
3. certain parasitic worms (IgE also important)
4. some cancers
5. Last defence/immune (surveillance)
6. Certain venoms.
How did allergies arise?
Hygiene hypothesis:
- cleanily westernised lifestyle caused a decreased encounter w/ organisms (e.g. farm animals) that woudl have pushed immune systems certain ways.
- immune system isn’t redirected producing IgE instead.
Old friends/microbiota hypothesis:
- used to having organisms around us
- entire microbiome considered in the environment
Epithelial barrier hypothesis:
- exposure to chemicals leads to damage of the epithelium in turn triggering T(c) type immunity.
What are some features of useful medicine?
- effective: have therapeutic action for which they are indicated.
- convenient: once a day tablet
- well-tolerant: slow side effects
- safe
- not too expensive
How do medicines act in the body?
- drugs bind to proteins that are called receptors.
- drugs that stimulate the receptor protein function are called agonists!
- drugs that bind to the active site of the receptor protein but do NOT stimulate the protein function are called antagonists!
What other medicines also protect against inflammation?
Cortisol and adrenaline
Talk about agentist response
What is high-throughput screening?
- brute force method
- very large compound library
- 10^5-10^6 distinct chemicals
- measure effect in high density plates
- program robots to do the repetitive work of adding solutions and measuring responses.
- HTS = provides starting point: medicinal chem and pharm generate structure-activity relationships and molecular models
What are biological medicines? Give examples.
-
What is hay fever?
- allergic rhinitis
- sympomatic inflammation of the nose induced by allergen inhalation by sensitive individuals.
- early/immediate allergic response (IgE crosslinking, degranulation, oedema).
- late-phase: reponse (4-8hrs post, nasal congestion).
- primary effect = worse on repeat.
How is Hay Fever Diagnosed?
- Clinical history
- Aeroallergen skin prick testing
- specific IgE testing/RAST
How is hay fever treated?
- minimization/avoidable
- intranasal corticosteroids
- thunderstorm asthma education if rye grass pollen sensitized.
- allergen immunotherapy
- treating other diseases
What is asthma?
- inflammatory disease of the lungs.
- variable airflow obstruction due to smooth muscle bronchoconstriction.
-
Reproduction26
-
Respiration24
-
Seeding27
-
Excretion22
-
Movement25
-
Fossil Records16
-
Evolution8
-
Hardy-Weinberg Theorem8
-
Natural Selection12
-
Mutations11
-
Gene Flow0
-
Molecular Genetics0
-
Life's complexity0
-
Metabolism0
-
When bodies fall apart0
-
Receiving Information0
-
Receiving Signals0
-
Transferring Information0
-
Fever and Thermoregulation23
-
Mitochondrial Disease1
-
Brain Development0
-
Gastroenteritis and Typhoid21
-
Asthma29
