Hypersensitivity Flashcards
What is hypersensitivity?
A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign agent
What is an allergen?
An antigen that causes allergy
What is type 1 hypersensitivity?
An allergy
Is intolerance different to allergy?
yes as there is no immunological reaction
Why is type 1 hypersensitivity sometimes called ‘immediate hypersensitivity’?
As it occurs rapidly in response to an allergen
What is type 1 hypersensitivity mediated by?
IgE
What is meant by the term ‘atopy’?
When an individual has a genetic predisposition for allergy
Type 1 hypersensitivity can lead to anaphylaxis. What is this?
An acute, serious allergic response
What are examples of inhaled materials that can cause an allergic reaction?
- Plant pollens
- Dander off of animals
What are examples of injected materials that can case an allergic reaction?
- Insect venoms
- Drugs
What are examples of ingested materials that can cause an allergic reaction?
- Food
- Orally administered drugs
What are examples of contacted materials that can cause an allergic reaction?
- Plant leaves
- Metals
What are haptens?
- Small molecules, which when combined with a larger molecule such as a carrier protein, can elicit the production of antibodies that can elicit an immune response
- Some drugs can act as haptens and induce antibody-mediated allergic reactions
What does IgE do?
- IgE producing B cells are activated during sensitisation (first exposure)
- IgE binds to Fc receptor on mast cells or CD63 on basophils
- IgE recognises allergen and next exposure binds rapidly causes immediate degranulation (elicitation)
What are examples of cutaneous (skin) atopy - wheal & flare?
- Urticaria (itchy rash)
- Allergic rhinitis (hay fever)
- Atopic dermatitis (allergic eczema)
- Asthma (lower respiratory tract)
- Food allergies (i.e. proven immunological response - not intolerance)
What is systemic anaphylaxis?
- Anaphylactic shock (mast cells degranulate all over the body)
- Three potential fatal reactions:
- Laryngeal oedema - suffocation
- Bronchiole constriction - Suffocation
- Peripheral oedema - Fluid loss from blood vessels causes hypotension (abnormally low blood pressure) and heart attack
What 4 tests can you use for type 1 allergy testing?
- Skin prick test
- Blood test
- Patch test
- Food challenge
Explain the procedure for a type 1 allergy skin prick test?
- First test to be done when looking for an allergen
- Results within about 20 minutes
- Skin pricked with a tiny amount of the suspected allergen
- Skin around the prick will become itchy, red and a wheal will appear
What is a type 1 allergy blood test?
- Specific IgE test
- Measures blood IgE antibody levels in response to allergen
What is a type 1 allergy patch test?
- tests if skin reaction due to contact with specific allergen
- Small amount of allergen added to metal discs taped to your skin for 20 mins and reaction monitored
What is a type 1 allergy food challenge?
- Diagnose food allergy
- Subject given gradually increasing amounts of the suspected food to which they are allergic and their reaction monitored
- Can only test one food at each appointment
- Has to be conducted in an ITU setting (danger to patient)
What are the possible treatments of a type 1 allergy?
- Avoid allergen (reaction can get worse with exposure)
- Drugs
- Immunological treatment
What drugs can be used to treat type 1 allergies?
- Anti-histamines - compete with histamine for receptors
- Hydrocortisone - block histamine synthesis
- Cromoglycate - Stabilises mast cells - stops histamine release
- Epinephrine - best immediate treatment for anaphylactic shock
- Reverses effects of granules
- Quick action but short duration
What is immunological treatment - hypo-sensitisation?
- repeat injections of allergen
- May work by shifting from IgE to IgG production
What do anti-histamines do?
- Target receptors
- Histamine receptors are never on or off: they switch between the 2 states
- When add histamine - pushes receptor to active form
- When add blockers (inverse agonists) - pushes it back to inactive form
What is meant by a biphasic anaphylactic response?
- Recurrences several hours after resolution of initial symptoms
- Should observe patients for up to 12 horse after patient recovery from initial episode (another flare could be fatal if patient doesn’t have another EpiPen)
What are the functions of epinephrine?
- Increases peripheral vascular resistance
- Improves blood pressure and coronary perfusion
- Reverses peripheral vasodilation
- Decreases angioedema
- Causes bronchodilation
- Increases intracellular cAMP in mast cells and reduces release of inflammatory mediators
What do type 2 hypersensitivity reactions involve?
- Involves activation of complement by IgG or IgM binding to an antigen cell (cell surface antigens)
In type 2 hypersensitivity what are cells lysed by?
- Membrane attack complex formation (complement)
- Antibody dependent cell mediated cytotoxicity (NK cells)
What is a haemolytic transfusion reaction?
- Giving the patient the wrong blood type
- IgM isohemagglutinins bind red blood cells activating complement
- Rapid intravascular lysis and hemaggluination
- Can cause renal failure and death
What is the treatment and prevention of haemolytic transfusion reaction?
- Treatment is to stop transfusion immediately and give diuretics
- Prevention is by cross-matching (blood type)
What are type 3 hypersensitivity reactions?
- Reactions against soluble antigens circulating in serum
- Antibody-antigen immune complexes are deposited in organs:
- Activate compliment
- Induce neutrophil recruitment
- Cause inflammatory damage
Give examples of type 3 hypersensitivity reactions?
- Arthritis
- Serum sickness
- Oral erythema multiforme
What is an arthus reaction and what is the process of this?
- Intradermal injection of antigen or vaccination
- Antigen-antibody complexes deposited in localised blood vessel walls
- Localised vasculitis response
- Complement activation:
- C3a/C5a chemotactic for neutrophils
- Frustrated phagocytes bind C3b on complexes but can’t phagocytose so dump granules causing damage
- Causes degranulation of mast cells
What is serum sickness?
- A systemic arthus reaction
- Antibody-antigen complexes circulate and lodge in many different tissues
What are the symptoms of serum sickness?
- Vasculitis
- Rash
- Fever
- Joint pain/swelling
What is oral erythema multiform characterised by?
Crusty blistering of oral mucosa
What is oral erythema multiform caused by?
Deposition of immune complexes (IgM) in the microvasculature of the oral mucous membrane
- Can be caused by hypersensitivity to drugs
What are type 4 hypersensitivity reactions caused by?
- T cell mediated hypersensitivity (no antibodies)
- Localised T cell reaction at site of encounter of contact antigens (contact dermatitis)
- Includes both CD4+ (inflammation induced damage) and CD8+ (direct damage of cells)
Why are type 4 hypersensitivity reactions sometimes called ‘delayed hypersensitivity’?
It takes time to recruit T cells
What type of test can be used to determine type 4 hypersensitivity reactions?
- Patch test
- Left for 48 hours then look for results
Type 4 hypersensitivity reactions have a role in which systemic diseases?
- TB
- Chron’s
- Sarcoidosis