Hypersensitivity and Allergy Flashcards by Alexandra Chan

What is immune tolerance

Appropriate immune tolerance occurs to self, and to foreign harmless proteins:
Food, pollens, other plant proteins, animal proteins, commensal bacteria

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What does immune tolerance involve

Involves antigen recognition and generation of regulatory T cells and regulatory (blocking) antibody (IgG4) production

Antigen recognition in context of “danger” signals leads to immune reactivity, absence of “danger” to tolerance

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What can hypersensitivity reactions be a response to

Harmless foreign antigens (allergy, contact hypersensitivity)
Autoantigens (autoimmune diseases)
Alloantigens (graft rejection)

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What are the types of hypersensitivity reactions

Type I : Immediate Hypersensitivity
Type II : Antibody-dependent Cytotoxicity
Type III : Immune Complex Mediated
Type IV : Delayed Cell Mediated

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Give examples of type I (immediate) hypersensitivity

Anaphylaxis
Asthma
Rhinitis (seasonal, perennial)
Food Allergy

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What occurs on first antigen exposure for immediate hypersensitivity

Sensitisation not tolerance
IgE antibody production
IgE binds to Mast Cells and Basophils

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What occurs on second antigen exposure for immediate hypersensitivity

More IgE Ab produced
Antigen cross-links between IgE on Mast Cells/Basophils
Degranulation and mediator release

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What are the autoantibody targets for the following type II hypersensitivity diseases: myasthenia graves, pemphigus vulgarisms, glomerulonephritis and pernicious anaemia

Myasthenia gravis: postsynaptic nicotinic acetylcholine receptor at neuromuscular junctions

Pemphigus vulgaris: desmoglein (links keratinocyte desmosomes to the basement membrane)

Glomerulonephritis: glomerular basement membrane

Pernicious anaemia: intrinsic factor

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Give examples of autoimmune cytopenias

Haemolytic anaemia
Thrombocytopenia
Neutropenia

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What are the tests done for type II hypersensitivity and give an example

Immunofluorescence or ELISA

e.g. ELISA for anti-CCP (cyclic citrullinated peptide) antibodies for rheumatoid arthritis.

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Describe what occurs in type III (immune complex mediated) hypersensitivity

Formation of Antigen-Antibody complexes in blood
Deposition in blood vessels/tissue
Complement + cell activation
Activation of other cascades eg clotting
Tissue damage (vasculitis)

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Give examples of vasculitis and tissue damage from type III hypersensitivity

Systemic lupus erythematosus (SLE or lupus)

Vasculitides (which also cause systemic inflammation, such as polyarteritis nodosum).

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What may cause type IV (delayed) hypersensitivity reactions

Chronic graft rejection
GVHD
Coeliac disease
Contact hypersensitivity
Many autoimmune diseases (asthma, rhinitis, eczema)

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What is GVHD

graft vs host disease

a bone marrow transplant’s immune cell products rejecting their new host’s other tissues

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Which hypersensitivity reaction type is the most common

Type IV

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Describe the role of Th1 in type IV hypersensitivity reactions

Antigens are presented Th1
Th1 produces interferon-γ (IFN-γ)
IFN-γ activates macrophages to produce lots of TNF-α.
Th1s also produce IL-2, which stimulates CD8+ CTLs.
If the resulting inflammation is chronic, fibroblast growth factor (FGF) is also made by the Th1s, leading to fibrosis and angiogenesis.

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Describe the role of Th2 and CTL in type IV hypersensitivity reactions

Th2 - Involved in allergic responses, in chronic asthma and hayfever.

CTL - Kill virally infected cells.

What occurs in inflammation

immune cell recruitment to the sites of injury/infection and subsequent activation
Inflammatory mediators include complement, cytokines etc.

What are the features of inflammation

Vasodilatation, increased blood flow
Increased vascular permeability
Inflammatory mediators + cytokines
Inflammatory cells + tissue damage

What are the signs of inflammation

Redness
Heat
Swelling
Pain

What are the types of inflammation in allergy

Type I - Anaphylaxis, angioedema, urticaria - IgE mediated

Type II - Urticaria (chronic or idiopathic) - IgG mediated

Type I + IV (mixed) - asthma, hay fever, eczema

What does expression of disease require

Development of sensitisation to allergens instead of tolerance (primary response - usually in early life)
Further allergen exposure to produce disease (memory response - any time after sensitisation)

Describe the process of sensitisation in atopic airway disease

Protein antigen (inhaled) is taken up by endogenous cell
Dendritic cells process the allergen into peptides
Presentation of peptides to Cd4+ t cells
Th1, Treg, Th2 activation
Th2, once sensitised, produce IL-4 and IL-13
B cell proliferation and differentiation
IgE production from plasma cells

Describe what occurs in subsequent exposure from sensitisation in atopic airway disease

Dendritic cells take up antigen
Antigen processed into peptides
Presentation to memory Th2 cells
Production of IL-4, IL-5 and IL-13
IL-4, IL-13 = B-cells product IgE
IL-5 = Eosinophil recruitment and activation
Mast cells and T-cell mediated activation

What process in memory cell generation is blocked in atopy

when an allergen is presented to a naïve T cell, regulatory T cells stop memory generation via IL-10. This is blocked in atopy, hence sensitisation proceeds fully.

Describe eosinophils (proportion, location, recruitment, production, microscopic structure)

2-5% of circulating WBCs More are in tissues than in the bloodstream Recruited during allergic inflammation Generated in bone marrow Two-lobed nucleus Contain large granules of toxic proteins which can lead to tissue damage

Describe mast cells (location, receptors)

Only reside in tissues Have IgE as receptors on their cell membrane Crosslinking of IgE as antigen binds causes release of mediators:

Which mediators are released on crosslinking of IgE on mast cells

Pre-formed: histamine, cytokines, toxic proteins | Newly synthesised: leukotrienes, prostaglandins

Which immune cells are important in asthma and atopic eczema

neutrophils

What does chronic inflammation in asthma involve

``` Cellular infiltrate of Th2 cells and eosinophils Mucus plugging Smooth muscle hypertrophy Epithelial shedding Sub-epithelial fibrosis ```

What is asthma (in reference to the lungs) and what does it lead to

reversible generalised airway obstruction, leading to a chronic episodic wheeze. The bronchi are hyperresponsive and irritable. It leads to cough, mucus production, and breathlessness.

What can treatment of asthma involve

inhaled β2-adrenoceptor agonists (salbutamol) Short acting and/or longer-acting inhaled steroids Oral steroids Leukotriene antagonists Anti-IgE monoclonal antibodies.

What is hay fever

Hayfever is seasonal allergic rhinitis. If year-round, it is called perennial allergic rhinitis instead. Perennial allergic rhinitis is not due to pollen, but other allergens such as animal fur or dust mites.

What can treatment of hay fever involve

Antihistamines to combat sneezing, itching, and rhinorrhoea Nasal steroid spray for the blockage Cromoglycate can help children’s eyes.

What is eczema (where is it common, what does it result in, age of presentation and clearance)

A chronic itchy rash on the skin. Most common at the knee and elbow flexures It results in dry, cracked skin and can be complicated by infections (majority bacterial, sometimes HSV). It is generally a disease of childhood, as 50% of cases clear by age 7 and 90% by adulthood.

What can treatment of eczema involve

Topical steroid cream and emollients (moisturisers)

What symptoms does a mild food allergy cause

itchy mouth and lips, angioedema, and urticaria.

What symptoms does a severe food allergy cause

nausea, abdominal pain, diarrhoea, and in the worst cases anaphylaxis.

What can treatment of food allergy involve

Avoidance Anaphylaxis: Adrenaline Antihistamines Steroids

How are allergies tested for

Careful histories Skin prick testing Radioallergosorbent test (RAST), which checks for specific IgE antibodies in the blood Total IgE levels Lung function tests (for asthma)

What is immunotherapy useful for

Single antigen hypersensitivities (bee/wasp venom, pollen, dust mites).

What are the types of immunotherapy for hypersensitivity

Subcutaneous immunotherapy - requires 3 years of regular clinic attendance for injections Sublingual immunotherapy - can be done at home with pills