Pathophysiology of Respiratory Diseases I Flashcards
What is Asthma?
A chronic inflammatory condition typically categorised by episodes of reversible airflow limitation and bronchial hyperresponsiveness, where the patient experiences difficulty breathing (dyspnoea)
Describe the inflammatory/immune system component of the pathology of asthma
Individual develops a hypersensitivity to a specific stimulus ,e.g. allergen such as pollen, causing an inflammatory response upon subsequent exposures to that stimulus.
Describe the airway component of the pathophysiology of asthma
The allergen-induced inflammation release mediators that affect cellular function and produce limitations in tissue function (i.e. airflow), resulting in the generation of symptoms such as coughing, dyspnoea, excess mucus.
What happens to the airways during an asthma attack?
Inflammation of the airways generates pathological changes, mainly airway smooth muscle contraction and mucus hypersecretion, which reduce the size of the airway lumen and so increase airway resistance and decrease airflow.
Describe the sensitisation stage of allergic asthma
the immune system first encounters the allergen and develops an adaptive (antibody and lymphocyte mediated) immune response
Describe the allergic response stage of allergic asthma
Where the allergen is subsequently re-encountered, triggering the adaptive response previously primed during sensitisation. This generates an inflammatory response within the airways, producing symptoms.
Once the allergen is inhaled and enters the airway tissue, parts of the innate immune system such as the epithelium are stimulated to release pro-inflammatory mediators….what happens next?
Allergen is then encountered by APCs such dendritic cells and macrophages. The antigen is then engulfed and processed. An antigen is displayed on the surface of the APC
The antigen on the APC is presented to a naïve T helper cell with an appropriate T cell receptor….what happens next?
Activation of the T cell will enable it to mature into a Th2 cell. This will then interact with a B cell which will initiate proliferation and production of IgE antibodies that bind to the allergen antigen
The IgE antibodies produced then circulate and bind (via their heavy chain/Fc region) IgE receptors on granulocytes such as mast cells….what does this allow?
When IgE is bound to its receptor in this way, the light chain/Fab region is still displayed, enabling antigen binding.
How do Beta-2 agonists induce ASMC relaxation via AC & PKA
Beta-2 agonist binds to beta-2 adrenoceptor which is a Gs protein coupled receptor. This causes an increase in Adenylyl Cyclase (AC) which causes ATP->cAMP which causes an increase in PKA which results in a decrease in Ca2+ mobilisation and sensitivity which causes muscle relaxation.
How do corticosteroid drugs reduce asthmatic inflammation?
Corticosteroid diffuses through cell membrane and binds to glucocorticoid receptor. This drug-receptor complex translocates to the nucleus and binds to DNA and affects transcription resulting in an altered transcription gene as corticosteroids increase or decrease expression of the specific gene e.g. increase anti-inflammatory genes. The gene is then translated into a protein.
What do T helper 2 cells do?
Stimulates B cells to produce IgE.
Releases cytokines that coordinate response
(eosinophil proliferation & migration to
airways)
Produces IL-4, IL-5, IL-13
What do B-cells do?
Production of antibodies that bind allergen
Produce IgE antibodies
What do Mast cells do?
Allergen-induced degranulation (allergen
binds IgE-FCERI receptor complex)
Produces leukotrienes and prostaglandins
What do Eosinophils do?
Cytokine-induced degranulation (release of
inflammatory/cytotoxic mediators)
Produces ROS, proteolytic enzymes, leukotrienes
