Hypersensitivity And Allergy Flashcards by Anas A

Describe appropriate immune tolerance, in terms of what it occurs in response to and what it involves.

Appropriate immune tolerance occurs to self, and to foreign harmless proteins.
Involves antigen recognition and generation of regulatory T cells and regulatory antibody (IgG4) production.

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What are hypersensitivity reactions usually mounted against?

Harmless foreign antigens
Autoantigens
Alloantigens

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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

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Describe the mechanism of type 1 hypersensitivity?

On 1st antigen exposure you get sensitisation – IgE is produced, which binds to mast cells and basophils

On subsequent antigen exposure, antigen cross-links the IgE on the mast cells causing degranulation and release of inflammatory mediators

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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 (Ab mediated blood cell destruction) e.g. autoimmune haemolytic anaemia, thrombocytopenia, neutropenia

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State the type of antibody responsible for the different organ specific autoimmune diseases.

Myasthenia gravis (Anti-acetylcholine R Ab)
Glomerulonephritis (Anti-glomerular basement membrane Ab)
Pemphigus vulgaris (Anti-epithelial cell cement protein Ab)
Pernicious anaemia (Intrinsic factor blocking Abs)

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2 Tests for specific autoantibodies?

Immunofluorescence

ELISA e.g. Cyclic Citrullinated Peptide Abs for Rheumatoid Arthritis

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What is type 3 immune complex mediated hypersensitivity characterised by?

Formation of Antigen-Antibody complexes in blood
Immune complexes deposit in blood vessels/tissues => complement and cell activation => activation of other cascades e.g. clotting => tissue damage (vasculitis)

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Give some examples of diseases caused by delayed type hypersensitivity.

Chronic graft rejections
Graft-versus-host disease
Coeliac disease

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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

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What are three important cytokines released by Th2?

IL-4
IL-5
IL-13

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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

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State four features of inflammation. What are the signs?

Vasodilatation
Increased vascular permeability
Inflammatory mediators & cytokines
Inflammatory cells & tissue damage

Redness
Heat
Swelling
Pain

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What is atopy?

A form of allergy in which there is a hereditary or constitutional tendency to develop hypersensitivity reactions in response to allergens

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How common is atopy?

Very common – about 50% of young adults in the UK

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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

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Among which age group is atopy most common?

Teens

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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) ```