Hypersensitivity and Allergy Flashcards by Georgia Leggett

What are hypersensitivity reactions usually mounted against?

Harmless foreign antigens (allergy)
Autoantigens (AI disease)
Alloantigens (Graft rejection)

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What are the 4 types 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

1st exposure: sensitisation: IgE is produced, which binds to mast cells + basophils
2nd exposure: antigen cross-links the IgE on mast cells causing degranulation + release of inflammatory mediators

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Give examples of Type 2 hypersensitivity diseases

Organ specific AI diseases: myasthenia gravis, glomerulonephritis, pemphigus vulgaris, pernicious anaemia
AI cytopenias: AI haemolytic anaemia, thrombocytopenia, neutropenia

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What are the consequences of immune complex formation in type 3 hypersensitivity?

Immune complexes deposit in tissues, activate complement + cause cell recruitment + activation
Can cause tissue damage e.g. SLE

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3 examples of diseases caused by Th1 cell mediated delayed type hypersensitivity.

Chronic graft rejections
Graft-versus-host disease
Coeliac disease

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Describe the mechanism of Th1 and cytotoxic T cell mediated delayed type hypersensitivity.

Transient/ persistent antigen is presented to T cells, which then activate macrophages + CTLs
Activated macrophages produce TNF-alpha, which is responsible for much of the tissue damage

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What are 3 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)

Type 3: soluble antigens

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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?

Common ~50% of YAs in the UK

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Genetic risk factors of atopy

~80% of atopics have a family history

Genetic component is polygenic but genes of IL-4 cluster + 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

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What 4 other environmental factors affect atopy?

Family size (higher in small families)
Infections (early life infections protect)
Animals (early exposure protects)
Diet

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What type of hypersensitivity is responsible for anaphylaxis, urticaria and angioedema?

Type 1 hypersensitivity

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What type of hypersensitivity is responsible for chronic urticaria?

Type 2 hypersensitivity

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What type of hypersensitivity is responsible for asthma, rhinitis and eczema?

Type 1 + type 4 hypersensitivity

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Describe sensitisation in atopic airway disease.

Naive T cells are exposed to the antigen by APCs
Differentiate into: Th1 cells (producing IFN-gamma), T regs or Th2 cells
Th2 cells produce IL4 +13 leading to B cell activation
B cells differentiate into plasma cells which produce IgE antibodies specific to antigen

Describe what happens in 2nd exposure to the allergen in atopic airway disease

Allergens are presented by APCs to memory Th2 cells, which release IL-5, causing eosinophil degranulation
Th2 cells also release IL-4 + IL-13, which stimulate production of IgE by plasma cells
Antigens crosslink the IgE on the surface of mast cells causing degranulation

What percentage of blood leukocytes are eosinophils?

0-5%

Describe the appearance of eosinophils.

Bi-lobed nucleus

Contains large granules of toxic proteins

What receptors do mast cells have on their cell surface? What does cross linking of these receptors result in?

IgE receptors

Mediator release

What mediators are released by mast cells?

Preformed: histamines, cytokines, toxic proteins

Newly synthesised: leukotrienes, prostaglandins

What percentage of blood leukocytes are neutrophils? Describe the appearance of neutrophils

55-60% Multi-lobed nucleus Granules containing digestive enzymes

What 3 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 bronchi

Describe 5 changes seen in a patient with chronic asthma.

Airway lumen is narrowed + wall is grossly thickened: Cellular infiltration by Th2 lymphocytes + eosinophils Smooth muscle hypertrophy Mucus plugging Epithelial shedding Subepithelial fibrosis

State 6 important clinical features of asthma.

``` Chronic episodic wheeze Bronchial hyper-responsiveness Cough Mucus production Breathlessness Reduced + variable peak expiratory flow (PEF) ```

What can allergic eczema lead to sensitisation of?

House dust mites: their proteins can penetrate dry, cracked skin

3 symptoms of a mild reaction to a food allergy

Itchy lips + mouth Angioedema Urticaria

4 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 5 symptoms of anaphylaxis.

``` Itchiness around mouth, pharynx + lips Swelling of the lips + throat Wheeze, chest tightness, dyspnoea Faintness, collapse Diarrhoea + vomiting ```

How can you test for allergies?

Skin prick test

What is the emergency treatment of anaphylaxis?

EpiPen + kit Adrenaline Antihistamine Steroid

Describe the step-by-step treatment of asthma.

Step 1: short acting B-2 agonist (e.g. salbutamol) Step 2: low-moderate dose inhaled steroids (e.g. beclomethasone) Step 3: add long acting bronchodilators or a leukotriene receptor antagonist + high dose inhaled steroids Step 4: add courses of oral steroids

What are the 2 types of immunotherapy that are used to develop tolerance in patients?

``` Subcutaneous immunotherapy (SCIT) Sublingual immunotherapy (SLIT) ```

What common feature is present in all hypersensitivity reactions? What causes this and what are the clinical signs?

``` Inflammation Vasodilation causes increased blood flow Increased vascular permeability Inflammatory mediators + cytokines Inflammatory cells + tissue damage Redness, Heat, Swelling, Pain ```

List 4 diseases where type 1 sensitivity plays a key role

Anaphylaxis Asthma Rhinitis Food allergy

What are the 4 most commonly effected tissues in type 3 hypersensitivity reactions?

Renal Skin Joints Lung

Which hypersensitivity states are neutrophils particularly important in?

Virus induced asthma Severe asthma Atopic eczema

List 4 symptoms of allergic rhinitis

Sneezing Rhinorrhoea Itchy nose + eyes Nasal blockage, sinusitis, loss of smell/ taste

What are 3 treatment options for allergic rhinitis?

Anti-histamines Nasal steroid spray Cromoglycate

What are the treatment options for eczema?

Emollients | Topical steroid cream