Hypersensitivity and Allergy Flashcards
What are hypersensitivity reactions usually mounted against?
Harmless foreign antigens
Autoantigens
Alloantigens
What are the four type of hypersensitivity reaction?
Type 1 – immediate hypersensitivity
Type 2 – antibody-mediated cytotoxicity
Type 3 – immune complex mediated
Type 4 – delayed cell mediated
Describe the mechanism of type 1 hypersensitivity?
On 1st exposure you get sensitisation – IgE is produced, which binds to mast cells and basophils
On subsequent exposure, antigen cross-links the IgE on the mast cells causing degranulation and release of inflammatory mediators
What types of diseases are examples of type 2 hypersensitivity?
Organ specific autoimmune diseases: e.g. myasthenia gravis, glomerulonephritis, pemphigus vulgaris, pernicious anaemia
Autoimmune cytopenias e.g. autoimmune haemolytic anaemia, thrombocytopenia, neutropenia
What are the consequences of immune complex formation in type 3 hypersensitivity?
Immune complexes deposit in tissues and activate complement and cause cell recruitment
This can cause tissue damage
Give some examples of diseases caused by delayed type hypersensitivity.
Chronic graft rejections
Graft-versus-host disease
Coeliac disease
Describe the mechanism of delayed type hypersensitivity.
The transient/persistent antigen is presented to T cells, which then activate macrophages and CTLs
Activated macrophages produce TNF-alpha, which is responsible for much of the tissue damage
What are three important cytokines released by Th2?
IL-4
IL-5
IL-13
What is the difference between the antigens involved in type 2 and type 3 hypersensitivity?
Type 2 – insoluble antigens (cell surface or matrix bound antigens)
Type 3 – soluble antigens
What is atopy?
A form of allergy in which there is a hereditary or constitutional tendency to develop hypersensitivity reactions in response to allergens
How common is atopy?
Very common – about 50% of young adults in the UK
List some genetic risk factors of atopy.
About 80% of atopics have a family history
The genetic component is polygenic but genes of the IL-4 cluster and genes on chromosome 11q have been linked to atopy
Among which age group is atopy most common?
Teens
Describe the gender difference in asthma
Males – asthma in childhood is more common
Females – asthma in adulthood is more common
What other environmental factors affect atopy?
Family size, infections, animals, diet
What type of hypersensitivity is responsible for anaphylaxis, urticaria and angioedema?
Type 1 hypersensitivity
What type of hypersensitivity is responsible for chronic urticaria?
Type 2 hypersensitivity
What type of hypersensitivity is responsible for asthma, rhinitisand eczema?
Type 1 and type 4 hypersensitivity
Describe sensitisation in atopic airway disease.
T cells are naïve before they have seen their antigen
Once the T cells are exposed to the antigen by APCs, they can become Th1 cells (producing IFN-gamma), T regs or Th2 cells Th2 cells lead to the activation of B cells and the production of IgE antibodies
Describe what happens in second exposure to the allergen.
In second exposure, the allergens are presented by APCs to memory Th2 cells, which then release IL-5, which causes eosinophil degranulation
Th2 cells also release IL-4 and IL-13, which stimulate production of IgE by plasma cells
The antigens crosslink the IgE on the surface of mast cells causing degranulation
What percentage of blood leukocytes are eosinophils?
2-5%
Describe the appearance of the nucleus of eosinophils.
Bilobed
What receptors do mast cells have on their cell surface?
IgE receptors
What mediators are released by mast cells?
Preformed: histamines, cytokines, toxic proteins
Newly synthesised: leukotrienes, prostaglandins
What percentage of blood leukocytes are neutrophils?
55-60%
What three processes cause airway narrowing in an acute asthma attack?
Vascular leakage leading to airways wall oedema
Mucus secretion fills up the lumen
Smooth muscle contraction around the bronch
Describe the changes seen in a patient with chronic asthma.
The lumen of the airway is narrowed and the airway wall is grossly thickened
There will be cellular infiltration by Th2 lymphocytes and eosinophils
There will be smooth muscle hypertrophy, mucus plugging, epithelial shedding and subepithelial fibrosis
State some important clinical features of asthma.
Chronic episodic wheeze Bronchial hyperresponsiveness Cough Mucus production Breathlessness Reduced and variable peak expiratory flow (PEF)
What can allergic eczema lead to sensitisation of?
House dust mites – their proteins can get through dry, cracked skin
What type of hypersensitivity is food allergy?
Type 1 hypersensitivity (IgE)
What are the symptoms of a mild reaction to a food allergy?
Itchy lips and mouth
Angioedema
Urticaria
What are the symptoms of a severe reaction to a food allergy?
Nausea
Abdominal pain
Diarrhoea
Anaphylaxis
What is anaphylaxis?
Severe generalised allergic reaction
What is anaphylaxis caused by?
Generalised degranulation of IgE sensitised mast cells
State some symptoms of anaphylaxis.
Itchiness around mouth, pharynx and lips Swelling of the lips and throat Wheeze, chest tightness, dyspnoea Faintness, collapse Diarrhoea and vomiting
How can you test for allergies?
Skin prick test
What is the emergency treatment of anaphylaxis?
Adrenaline
Describe the step-by-step treatment of asthma.
Step 1: short acting beta 2 agonist (e.g. salbutamol)
Step 2: low-moderate dose inhaled steroids (e.g. beclomethasone, budesonide, fluticasone)
Step 3: add long acting beta 2 agonist or a leukotriene receptorantagonist + high dose inhaled corticosteroids
Step 4: add courses of oral steroids
What are the two types of immunotherapy that are used to develop tolerance in patients?
Subcutaneous immunotherapy (SCIT) Sublingual immunotherapy (SLIT)
