Lecture 8- allergy and asthma Flashcards
Which of these correctly describes what biologic drugs are?
Drugs based on molecules made by living organisms
What process enables cells to migrate into tissues from the blood?
Trans-endothelial migration
Which of these statements about cytokine receptor signalling is correct?
Cytokine binding to the receptor triggers phosphorylation of Janus Kinases
Some cytokines are used in a ‘paracrine’ manner - i.e. used by the same cell that make them
But most cytokines act on other cells
The receptors they bind to all send positive signals to the nucleus.
Depending on the cytokine, this may increase or decrease the immune response
See the Molecular Immunology lecture for revision
Which of these statements about costimulatory molecules is correct?
They enhance the signals delivered through the T cell receptor
what is an allergic disorder?
An inappropriate immunological response to a harmless stimuli
E.g. pollen, house dust mite
Can affect different areas of the body depending on exposure
Atopic eczema
Asthma
Allergic rhinitis (e.g. hay fever)
Food allergy
In an extreme form
Anaphylaxis
Acute severe asthma
what is an atopy?
the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma and atopic dermatitis (eczema).
what is immediate hypersensitivity?
Happen in minutes to hours
Usually mediated by IgE
Examples - hay fever, food allergies
what is delayed type hypersensitivity?
Happen over a longer period of time - 2-3 days
Usually mediated by T cells
Examples include response to poison ivy
what are allergic responses?
memory responses
1. Allergen penetrates epithelial cell barrier
2. Activated DCs move to lymphoid organs carrying the allergen
3. DCs activate allergen specific T cells
4. T cell proliferate
5. CD4 T cell help B cell make IgE that can bind to the allergen
6. T and B cells migrate out of the lymph node
7. T & B cells migrate to tissue and some become resident. IgE bind to tissue mast cells
what are the consequences of histamines?
Increase vascular permeability leading to swelling
Itch
Smooth muscles: contraction -leading to difficulty in breathing
Increased heart rate
Increased gastric acid secretion
Can reduce effects of allergies with over the counter anti-histamines
what is an epipen?
Epinephrine (adrenaline) device that enables rapid delivery and counters the systemic effects of histamine release including vasoconstriction
what is allergic rhinitis?
Generally, responds to antihistamine treatment
The causative allergen is often known e.g., pollen, house dust mite
May be seasonal (intermittent) or present all year round (persistent)
Generally, affects the upper respiratory tract
what is asthma?
2/3 of rhinitis patients also have asthma
Effects the lower airways
No treatment benefit with antihistamines
Allergic trigger sometimes known e.g., cat dander
Can range from mild to severe symptoms
Severe asthma can be fatal
what are symptoms of asthma?
Asthma is a chronic disease characterised by cough, shortness of breadth, and chest tightness
In childhood onset asthma associated with atopy, virus infection. Increased risk if born by Caesarean section or antibiotic use at young age
Exposure to a trigger leads to reversible airway obstruction
Triggers can be allergens, but also environmental changes, e.g. cold air
Characterised by immune cell infiltration to the airways and increased mucous production
These symptoms can be treated with corticosteroids
Permeant compromised airway result from airway remodelling including thickening of basement membrane and fibrosis
These changes cannot be reversed
what are treatments for type 2 high asthma?
Inhaled corticosteroids
Very effective anti-inflammatory agent
Prevent asthma deaths
Reduce hospital admissions
Prevent hospital readmissions
Reduce inflammatory molecules in vivo
The best strategy we have at present to treat airways inflammation
Steroids induce eosinophil apoptosis
Particularly effective in combination with long acting beta agonists that relax airway smooth muscle cells
can B cells switch their constant domains?
On naïve B cells (and some memory B cells)
and On activated/memory B cells after class switching
what is type 2 high asthma?
Trigger: Allergens
Release of cytokines including IL-33
Type 2 High Asthma
Immune infiltrate is dominated by Th2 cells, eosinophils and IgE bound mast cells
Associated with allergic responses
Often associated with early age onset
Can be treated by steroids and biologics
Eosinophils & other type 2 cells
Release of type 2 cytokines that drive, smooth muscle contraction and mucous production
what is type 2 low asthma?
Trigger: Cigarette smoke, Viruses, Pollution
Epithelial cell damaged: Produce chemokine to attract neutrophils and cytokines including IL-1b and IL-6.
Type 2 Low Asthma
Immune infiltrate is dominated by neutrophils
More often late onset and linked to obesity
Unlikely to respond to steroids
neutrophils - Produce reactive oxygen species and elastase that cause epithelial cell damage and mucous release
what is mast cell degranulation
drives allergy symptoms
Allergen - e.g. animal dander, house dust mite antigen, pollen, insect bite
Allergen cross links IgE bound to mast cells
Mast cell ‘degranulates
Histamine release, Can have local and/or systemic effects
what are the Major effects on vascular systems and lungs during anaphylaxis?
1 - endothelial permeability fluid extravasation endema formation
2 - drop in blood pressure
3 - peripheral vasodilation reduction of venous return
4 - broncho / Faso constriction of pulmonary and coronary arteries
5 - anaphylactic shock and patient death
