Allergies Flashcards
Define hypersensitivity
The antigen-specific immune responses that are either inappropriate or excessive and result in harm to the host
The underlying mechanisms are those employed by the host to also fight infection.
Common features of hypersensitivity?
Sensitisation phase - on first encounter with the antigen. No clinical manifestation because don’t have the antibodies. Begin producing the antibodies
Effector phase - clinical pathology upon re-exposure to the same antigen
Describe a type I (immediate) hypersensitive reaction
Happens in
Describe type II hypersensitivity reactions
Antibody mediated
Within 5-12 hours
IgM and IgG are directed against the cell membrane/surface
Describe type IV hypersensitivity reactions
24-48 hours
Environmental infectious agents and self-antigens
Not antibody mediated
Cell mediated
Describe type III hypersensitivity reactions
Immune complex mediated to soluble antigens
3-8 hours
Symptoms of a type I reaction?
Hives
Itchiness
Red face/skin
Swollen lips
Pathophysiology of a type I reaction?
Anaphylaxis caused by immune response
IgE binds to antigen which activates receptors on the mast cells and basophils
Cause release of granule contents including histamine and chemokines
Cause different clinical symptoms depending on where they are released.
What do histamine and chemokines do depending on where they are released in a type I reaction?
Contraction of bronchial smooth muscle
Vasodilation
Increased fluid leakage from capillaries
Depress action of heart muscle
How do you get the anaphylaxis when not caused by immune response?
Due to an agent that directly damages mast cells and basophils
Causes de granulation
Caused by contrast medium for X Rays, opioids, temperature, vibration
How are skin prick tests for allergies done?
Small amounts of suspected allergens are introduced to the skin
Use histamine as a positive control
If patient is allergic, beg a visible inflammatory reaction
-slight reddening or wheel and flare
How does the allergen cause a reaction in skin prick tests?
Binds to mast cells in the epidermis to trigger a local reaction
- dilation
- increased permeability
How does manifestation of an allergic reaction in the face occur?
Mast cells are activated in the deep dermis
Angioedema happens
Can be fatal if it affects upper respiratory airways
Can affect eyes, lips, tongue
Systemic manifestation of an allergic reaction?
When mast cells are activated systemically
- hypotension due to fluid loss
- CVS collapse
- angioedema
- wheezing
- generalised urticaria
Difference between urticaria and angioedema?
Urticaria is swelling of the superficial part of the skin - hives or rash
Angio-oedema occurs when deeper tissues in the dermis and subcutaneous tissue are involved and become swollen
How does administration of adrenaline treat anaphylaxis?
Reverses peripheral vasodilation
Less oedema
Reverses airways obstruction
Increased force of myocardial contraction
Inhibits mast cell activation by β2 receptors
What else needs to be done while treating anaphylaxis?
Monitor pulse, BP, ECG, oximetry
How to diagnose an allergy?
Clinical history - atopy, allergens, seasonality, route of exposure
Blood tests - serum allergen-specific IgE, serum mast cell tryptase, histamine (indicates systemic de granulation)
Skin prick tests
Challenge tests for food and drug allergies
Management of allergies?
Allergen avoidance and elimination Education - recognise symptoms, how to use EPIPEN Median alert identification bracelet Drugs Allergen desensitisation
What drugs can be used in the management of allergies?
Antihistamines
Corticosteroids
Anti IgE/IgG
Injectable adrenaline in an EPIPEN (0.5mg)
How is allergen desensitisation done?
Administration of increasing doses of allergen extracts over years
Given by injection or drops/tablets under the tongue (sublingual)
What are challenge tests?
To work out what the person is allergic to
Done in a hospital with resuscitation equipment near by
Small amounts of different allergen are given, see if there is a reaction
What are the mechanisms of type II hypersensitive reactions?
Antibody-dependent activation of complement
Antibody-dependent cell-mediated cytotoxicity
Antibody-mediated modulation of cellular function
What are some examples of type II reactions affecting function?
Grave’s disease - anti-thyroid stimulating hormone receptor Ab
Myasthenia gravis - anti-acetylcholine receptor Ab
Pernicious anaemia - anti-intrinsic factor Ab or anti-gastric parietal cells
Symptoms of pernicious anaemia?
Paraesthesia
Numbness
Cognitive changes
Visual disturbance
What are some type II reactions leading to tissue damage?
Good-pasture’s syndrome: anti-glomerular basement membrane -> glomerulonephritis and lung haemorrhage
Haematological disease
- Rhesus haemolytic anaemia
- Autoimmune haemolytic anaemia
- Transfusion reactions
How can rhesus haemolytic anaemia happen and what is the pathology?
Rh +ve father
Rh -ve mother carries Rh +ve fetus and antigens can enter the maternal blood during delivery
Mother produces anti-Rh antibodies
Another Rh+ fetus will cause anti-Rh Abs to cross the placenta and damage fetal RBCs
How is rhesus haemolytic anaemia tested for?
Direct/indirect Coomb’s test
Give some examples of type III hypersensitivity diseases
Rheumatoid arthritis - anti-rheumatoid factor IgG
Glomerulonephritis (infectious) - bacterial endocarditis/hep B
SLE
Damage caused by deposition of immune complexes in tissues
Give some examples of conditions associated with type IV hypersensitivity
Associated with granuloma formation
- TB
- Leprosy
- Schistosomiasis
- Sarcoidosis
- Type 1 diabetes
- Hashimoto’s thyroiditis
- RA (IgG)
- Coeliac disease
Complications of coeliac disease?
Hyposplenism
Lymphoma
