_The early phase allergic reaction_ In allergic individuals, exposure to allergens (substance to which IgE antibodies may be produced) leads to the rapid development of symptoms This reaction develops within ... or ... of exposure and results from the binding of allergens to pre-formed IgE antibodies on the surface of ... cells and ...

In allergic individuals, exposure to allergens (substance to which IgE antibodies may be produced) leads to the rapid development of symptoms This reaction develops within seconds or minutes of exposure and results from the binding of allergens to pre-formed IgE antibodies on the surface of mast cells and basophils

_Pharmacological effects of mast cell mediators and leukotrienes_ Histamine effects (mast cell activation and granule release): GI - Increased ... secretion, increased ... - ... of GI tract contents (diarrhea, vomiting) Airway - Decreased diameter, increased mucus ... - congestion and blockage of airways (wheezing, ..., ...) - swelling and mucus secretion in nasal passages Blood Vessels - Increased blood flow, increased ... - increased fluid in tissues causing increased flow of ... to ... nodes, increased cells and proteins in tissues, increased ... response in tissues

Histamine effects: GI - Increased fluid secretion, increased peristalsis - expulsion of GI tract contents (diarrhea, vomiting) Airway - Decreased diameter, increased mucus secretion - congestion and blockage of airways (wheezing, coughing, phlegm) - swelling and mucus secretion in nasal passages Blood Vessels - Increased blood flow, increased permeability - increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and proteins in tissues, increased effector response in tissues

_Pharmacological effects of mast cell mediators and leukotrienes_ Histamine effects (... cell ... and ... release): GI - Increased fluid secretion, increased peristalsis - expulsion of GI tract contents (...,...) Airway - Decreased diameter, increased mucus secretion - congestion and blockage of airways (..., ..., ...) - swelling and mucus secretion in nasal passages Blood Vessels - Increased blood flow, increased permeability - increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and proteins in tissues, increased effector response in tissues

Histamine effects (mast cell activation and granule release): GI - Increased fluid secretion, increased peristalsis - expulsion of GI tract contents (diarrhea, vomiting) Airway - Decreased diameter, increased mucus secretion - congestion and blockage of airways (wheezing, coughing, phlegm) - swelling and mucus secretion in nasal passages Blood Vessels - Increased blood flow, increased permeability - increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and proteins in tissues, increased effector response in tissues

_Clinical allergy syndromes: oral allergy syndrome_ Most ... type of food allergy amongst UK adults Ig... directed against pollen proteins ...-reacts with homologous proteins in plant-derived foods Oral itching upon exposure to raw fruit, nuts and vegetables In UK: Pollen = mainly ... Food = mainly ... fruits

Most common type of food allergy amongst UK adults IgE directed against pollen proteins cross-reacts with homologous proteins in plant-derived foods Oral itching upon exposure to raw fruit, nuts and vegetables In UK: Pollen = mainly birch Food = mainly Rosaceae fruits (such as apples, pears, quinces, apricots)

_Clinical allergy syndromes: oral allergy syndrome_ Most common type of food allergy amongst UK adults IgE directed against pollen proteins cross-reacts with homologous proteins in plant-derived foods Oral ... upon exposure to .. fruit, nuts and vegetables In UK: ... = mainly birch ... = mainly Rosaceae fruits

Most common type of food allergy amongst UK adults IgE directed against pollen proteins cross-reacts with homologous proteins in plant-derived foods Oral itching upon exposure to raw fruit, nuts and vegetables In UK: Pollen = mainly birch Food = mainly Rosaceae fruits

Allergy Flashcards by Chrissy Taaffe

The early phase allergic reaction

In allergic individuals, exposure to allergens (substance to which IgE antibodies may be produced) leads to the rapid development of symptoms
This reaction develops within … or … of exposure and results from the binding of allergens to pre-formed IgE antibodies on the surface of … cells and …

In allergic individuals, exposure to allergens (substance to which IgE antibodies may be produced) leads to the rapid development of symptoms
This reaction develops within seconds or minutes of exposure and results from the binding of allergens to pre-formed IgE antibodies on the surface of mast cells and basophils

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Allergen=substance to which … antibodies may be produced

Allergen=substance to which IgE antibodies may be produced

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In allergic individuals, exposure to … leads to the rapid development of symptoms

In allergic individuals, exposure to allergens leads to the rapid development of symptoms

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Basic mechanism of the early phase allergic reaction

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Events the follow mast cell IgE ligation

IgE binds its specific allergen
…-… of IgE antibodies by allergen leads to clustering of FcεR1 receptors
The intracellular portion of the receptor becomes …
The resulting intracellular cascade leads to cellular …
Mast cell ‘…’ releasing histamine, tryptase and other pre-formed mediators

IgE binds its specific allergen
Cross-linking of IgE antibodies by allergen leads to clustering of FcεR1 receptors
The intracellular portion of the receptor becomes phosphorylated
The resulting intracellular cascade leads to cellular activation
Mast cell ‘degranulates’ releasing histamine, tryptase and other pre-formed mediators

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Events the follow mast cell IgE ligation

IgE binds its specific allergen
Cross-linking of IgE antibodies by allergen leads to … of FcεR1 receptors
The … portion of the receptor becomes phosphorylated
The resulting … cascade leads to cellular activation
… cell ‘degranulates’ releasing …, tryptase and other pre-formed mediators

IgE binds its specific allergen
Cross-linking of IgE antibodies by allergen leads to clustering of FcεR1 receptors
The intracellular portion of the receptor becomes phosphorylated
The resulting intracellular cascade leads to cellular activation
Mast cell ‘degranulates’ releasing histamine, tryptase and other pre-formed mediators

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Delayed mediators – leukotrienes (allergy)

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Pharmacological effects of mast cell mediators and leukotrienes

Histamine effects (mast cell activation and granule release):
- GI - Increased … secretion, increased … - … of GI tract contents (diarrhea, vomiting)
- Airway - Decreased diameter, increased mucus … - congestion and blockage of airways (wheezing, …, …) - swelling and mucus secretion in nasal passages
- Blood Vessels - Increased blood flow, increased … - increased fluid in tissues causing increased flow of … to … nodes, increased cells and proteins in tissues, increased … response in tissues

Histamine effects:
- GI - Increased fluid secretion, increased peristalsis - expulsion of GI tract contents (diarrhea, vomiting)
- Airway - Decreased diameter, increased mucus secretion - congestion and blockage of airways (wheezing, coughing, phlegm) - swelling and mucus secretion in nasal passages
- Blood Vessels - Increased blood flow, increased permeability - increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and proteins in tissues, increased effector response in tissues

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Pharmacological effects of mast cell mediators and leukotrienes

Histamine effects (… cell … and … release):
- GI - Increased fluid secretion, increased peristalsis - expulsion of GI tract contents (…,…)
- Airway - Decreased diameter, increased mucus secretion - congestion and blockage of airways (…, …, …) - swelling and mucus secretion in nasal passages
- Blood Vessels - Increased blood flow, increased permeability - increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and proteins in tissues, increased effector response in tissues

Histamine effects (mast cell activation and granule release):
- GI - Increased fluid secretion, increased peristalsis - expulsion of GI tract contents (diarrhea, vomiting)
- Airway - Decreased diameter, increased mucus secretion - congestion and blockage of airways (wheezing, coughing, phlegm) - swelling and mucus secretion in nasal passages
- Blood Vessels - Increased blood flow, increased permeability - increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and proteins in tissues, increased effector response in tissues

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Examples of allergen sources

Allergens are almost always otherwise … environmental …
Of the thousands of environmental proteins that we meet, only a few hundred are recognised as allergens

Allergens are almost always otherwise innocuous environmental proteins
Of the thousands of environmental proteins that we meet, only a few hundred are recognised as allergens

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Give some examples of allergen sources

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General characteristics of allergens

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General characteristics of allergens

… (there are a few minor exceptions)
Physical properties that favour transition across … membranes
Biologically active, often …
Have moderate … with self-proteins

Proteins (there are a few minor exceptions)
Physical properties that favour transition across mucus membranes
Biologically active, often enzymes
Have moderate homology with self-proteins

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Clinical allergy syndromes: anaphylaxis

‘… …’ reaction
Systemic release of … causes generalised vasodilatation & fluid loss from circulation to tissues
- Cutaneous: hives, angioedema
- Gut … release: vomiting, diarrhoea
- Mucosal … release: laryngeal oedema, bronchoconstriction
- Circulation: vasodilatation, hypotension
Food, drugs and insect … commonest triggers in UK
Cardinal features: typical symptoms, multi-system and dramatic, … follows exposure to allergen and tends to improve fairly … thereafter

‘Generalised allergic’ reaction
Systemic release of histamine causes generalised vasodilatation & fluid loss from circulation to tissues
- Cutaneous: hives, angioedema
- Gut histamine release: vomiting, diarrhoea
- Mucosal histamine release: laryngeal oedema, bronchoconstriction
- Circulation: vasodilatation, hypotension
Food, drugs and insect venom commonest triggers in UK
Cardinal features: typical symptoms, multi-system and dramatic, rapidly follows exposure to allergen and tends to improve fairly quickly thereafter

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Clinical allergy syndromes: anaphylaxis

‘Generalised allergic’ reaction
Systemic release of histamine causes generalised … & fluid … from circulation to tissues
- Cutaneous: h.., angioedema
- Gut histamine release: V, …
- Mucosal histamine release: … oedema, broncho…
- Circulation: vaso…, …tension
…, drugs and insect venom commonest triggers in UK
Cardinal features: typical symptoms, multi-system and dramatic, rapidly follows exposure to allergen and tends to improve fairly quickly thereafter

‘Generalised allergic’ reaction
Systemic release of histamine causes generalised vasodilatation & fluid loss from circulation to tissues
- Cutaneous: hives, angioedema
- Gut histamine release: vomiting, diarrhoea
- Mucosal histamine release: laryngeal oedema, bronchoconstriction
- Circulation: vasodilatation, hypotension
Food, drugs and insect venom commonest triggers in UK
Cardinal features: typical symptoms, multi-system and dramatic, rapidly follows exposure to allergen and tends to improve fairly quickly thereafter

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Clinical allergy syndromes: oral allergy syndrome

Most … type of food allergy amongst UK adults
Ig… directed against pollen proteins …-reacts with homologous proteins in plant-derived foods
Oral itching upon exposure to raw fruit, nuts and vegetables
In UK:
- Pollen = mainly …
- Food = mainly … fruits

Most common type of food allergy amongst UK adults
IgE directed against pollen proteins cross-reacts with homologous proteins in plant-derived foods
Oral itching upon exposure to raw fruit, nuts and vegetables
In UK:
- Pollen = mainly birch
- Food = mainly Rosaceae fruits (such as apples, pears, quinces, apricots)

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Clinical allergy syndromes: oral allergy syndrome

Most common type of food allergy amongst UK adults
IgE directed against pollen proteins cross-reacts with homologous proteins in plant-derived foods
Oral … upon exposure to .. fruit, nuts and vegetables
In UK:
- … = mainly birch
- … = mainly Rosaceae fruits

Most common type of food allergy amongst UK adults
IgE directed against pollen proteins cross-reacts with homologous proteins in plant-derived foods
Oral itching upon exposure to raw fruit, nuts and vegetables
In UK:
- Pollen = mainly birch
- Food = mainly Rosaceae fruits

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Clinical allergy syndromes: airway disease

R…
- Sneezing, rhinorhoea, blockage due to a type … allergy
… airway obstruction
- Wheeze due to type … allergy
Allergens/ symptoms may be:
- Seasonal: pollens, m…
- Episodic: o.., animal dander
When symptoms are chronic, the inflammation becomes established and cannot be explained simply in terms of mast cell …

Rhinitis
- Sneezing, rhinorhoea, blockage due to a type 1 allergy
Lower airway obstruction
- Wheeze due to type 1 allergy
Allergens/ symptoms may be:
- Seasonal: pollens, moulds
- Episodic: occupational, animal dander
When symptoms are chronic, the inflammation becomes established and cannot be explained simply in terms of mast cell degranulation

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Clinical allergy syndromes: airway disease

Rhinitis
- S.., rhinorhoea, blockage due to a type 1 allergy
Lower airway obstruction
- … due to type … allergy
Allergens/ symptoms may be:
- Seasonal: P.., moulds
- Episodic: occupational, A.. dander
When symptoms are chronic, the inflammation becomes established and cannot be explained simply in terms of … cell degranulation

Rhinitis
- Sneezing, rhinorhoea, blockage due to a type 1 allergy
Lower airway obstruction
- Wheeze due to type 1 allergy
Allergens/ symptoms may be:
- Seasonal: pollens, moulds
- Episodic: occupational, animal dander
When symptoms are chronic, the inflammation becomes established and cannot be explained simply in terms of mast cell degranulation

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The immunological tightrope

The immune system is constantly challenged with antigens&must somehow decide how to respond
- … antigens vs non-…
- Dangerous infections vs … organisms
- … allergens such as foods and pollens

The immune system is constantly challenged with antigens&must somehow decide how to respond
- Self antigens vs non-self
- Dangerous infections vs commensal organisms
- Environmental allergens such as foods and pollens

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The immunological tightrope

The immune system is constantly challenged with antigens&must somehow decide how to respond
- Self antigens vs non-self
- … infections vs commensal organisms
- Environmental allergens such as … and …

The immune system is constantly challenged with antigens&must somehow decide how to respond
- Self antigens vs non-self
- Dangerous infections vs commensal organisms
- Environmental allergens such as foods and pollens

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Allergy - over the years:

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Chronic allergic inflammation: asthma

Patients with chronic asthma have on-going symptoms
Most patients are … to a variety of …. allergens
Biopsy shows inflammatory … and airway changes known as ‘re-modelling’ – thickened basement membrane and smooth muscle hyper..
The ‘early allergic reaction’ model does not provide a good explanation by itself

Patients with chronic asthma have on-going symptoms
Most patients are sensitised to a variety of airborne allergens
Biopsy shows inflammatory infiltrate and airway changes known as ‘re-modelling’ – thickened basement membrane and smooth muscle hyperplasia
The ‘early allergic reaction’ model does not provide a good explanation by itself

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Chronic allergic inflammation: asthma

Patients with chronic asthma have on-going symptoms
Most patients are sensitised to a variety of airborne allergens
Biopsy shows inflammatory infiltrate and airway changes known as ‘re-…’ – thickened … membrane and smooth muscle …
The ‘… allergic reaction’ model does not provide a good explanation by itself

Patients with chronic asthma have on-going symptoms
Most patients are sensitised to a variety of airborne allergens
Biopsy shows inflammatory infiltrate and airway changes known as ‘re-modelling’ – thickened basement membrane and smooth muscle hyperplasia
The ‘early allergic reaction’ model does not provide a good explanation by itself

_The late phase allergic reaction_ * The ... ... reaction to allergen is followed some hours later by a second ‘late phase reaction’ * Biopsy of the late phase shows infiltration with inflammatory cells – particularly ... T cells, eosinophils and ... cells; provides some insight into chronic allergic inflammation, and often used as an experimental model

* The **early** phase reaction to allergen is followed some hours later by a second ‘late phase reaction’ * Biopsy of the late phase shows infiltration with inflammatory cells – particularly **CD4** T cells, eosinophils and **mast** cells; provides some insight into chronic allergic inflammation, and often used as an experimental model

_T cell subsets_

_Th2-biased infiltrate in asthmatic lung_

_Alder allergy associated with Th2-biased responses to alder_

_T cell subsets and the Th2 hypothesis_ * Th2 responses to allergens have been ... associated with allergic disease * ... of allergic inflammation are rich in T cells expressing Th2 cytokines * T cells from allergic patients stimulated with ... in the laboratory produce Th2 cytokines * Plenty of reasons to believe that Th2 responses may be important in allergy: * IL-... is required for B cell class switching to IgE * IL-.. and IL-... promote mucus hypersecretion * IL-5 is required for ... survival * IL-9 recruits ... cells

* Th2 responses to allergens have been **consistently** associated with allergic disease * **Biopsies** of allergic inflammation are rich in T cells expressing Th2 cytokines * T cells from allergic patients stimulated with **allergen** in the laboratory produce Th2 cytokines * Plenty of reasons to believe that Th2 responses may be important in allergy: * **IL-4** is required for B cell class switching to IgE * **IL-4** and **IL-13** promote mucus hypersecretion * IL-5 is required for **eosinophil** survival * IL-9 recruits **mast** cells

_T cell subsets and the Th2 hypothesis_ * Th2 responses to allergens have been consistently associated with allergic disease * Biopsies of allergic inflammation are rich in T cells expressing Th2 cytokines * T cells from allergic patients stimulated with allergen in the laboratory produce Th2 cytokines * Plenty of reasons to believe that Th2 responses may be important in allergy: * IL-4 is required for B cell class switching to ... * IL-4 and IL-13 promote mucus ... * IL-... is required for eosinophil survival * IL-.. recruits mast cells

* Th2 responses to allergens have been consistently associated with allergic disease * Biopsies of allergic inflammation are rich in T cells expressing Th2 cytokines * T cells from allergic patients stimulated with allergen in the laboratory produce Th2 cytokines * Plenty of reasons to believe that Th2 responses may be important in allergy: * IL-4 is required for B cell class switching to **IgE** * IL-4 and IL-13 promote mucus **hypersecretion** * **IL-5** is required for eosinophil survival * **IL-9** recruits mast cells

* Biopsies of allergic inflammation are rich in T cells expressing Th... cytokines * T cells from allergic patients stimulated with allergen in the laboratory produce Th... cytokines

* Biopsies of allergic inflammation are rich in T cells expressing **Th2** cytokines * T cells from allergic patients stimulated with allergen in the laboratory produce **Th2** cytokines

_Chronic allergic disease: asthma (ACUTE responses)_ * Inflammatory mediators cause increased mucus ... and ... muscle contraction leading to airway ... * ... of cells from the circulation

* Inflammatory mediators cause increased mucus **secretion** and **smooth** muscle contraction leading to airway **obstruction** * **Recruitment** of cells from the circulation

_Chronic allergic disease: asthma (CHRONIC responses)_ * Chronic response caused by ... and ... products * Activated Th... cells and other inflammatory cells accumulate * Th... products lead to chronic disease * IL4: mucus hypersecretion * IL-13: bronchial hyper-responsiveness * IL-5: eosinophil recruitment * IL-9: mast cell recruitment * This model suggests a true role for T cells in chronic inflammation rather than just in causing IgE production

* Chronic response caused by **cytokines** and **eosinophil** products * Activated **Th2** cells and other inflammatory cells accumulate * **Th2** products lead to chronic disease * IL4: mucus hypersecretion * IL-13: bronchial hyper-responsiveness * IL-5: eosinophil recruitment * IL-9: mast cell recruitment * This model suggests a true role for T cells in chronic inflammation rather than just in causing IgE production

_Chronic allergic disease: asthma (CHRONIC responses)_ * Chronic response caused by cytokine and eosinophil products * Activated Th2 cells and other inflammatory cells accumulate * Th2 products lead to chronic disease * IL4: mucus ... * IL-13: bronchial ...-r... * IL-5: ... recruitment * IL-9: ... cell recruitment * This model suggests a true role for T cells in chronic inflammation rather than just in causing ... production

* Chronic response caused by cytokines and eosinophil products * Activated Th2 cells and other inflammatory cells accumulate * Th2 products lead to chronic disease * IL4: mucus **hypersecretion** * IL-13: bronchial **hyper-responsiveness** * IL-5: **eosinophil** recruitment * IL-9: **mast** cell recruitment * This model suggests a true role for T cells in chronic inflammation rather than just in causing **IgE** production

_Potential factors in the aetiology of allergy: genetics_ * Childhood allergy is ... predicted by presence of allergy in parents, but difficult to unpick relative contribution of ... * Numerous genetic risk factors identified, but none particularly compelling * Notable that the allergy epidemic has occurred too ... to be explained entirely by genetics

* Childhood allergy is **strongly** predicted by presence of allergy in parents, but difficult to unpick relative contribution of **environment** * Numerous genetic risk factors identified, but none particularly compelling * Notable that the allergy epidemic has occurred too **quickly** to be explained entirely by genetics

_Hygiene hypothesis: Strachan 1989_ * ... hygiene levels, ... pathogen load, helminth infection proposed to: * Skew immunity from Th... to Th... * Induce regulatory T cells * ... hygiene levels, ... pathogen load, absence of helminth infection proposed to: * Skew immunity towards Th... * Reduce production of regulatory T cells * Has proved resilient as a theory, but remains somewhat theoretical

* **Low** hygiene levels, **high** pathogen load, helminth infection proposed to: * Skew immunity from **Th2 to Th1** * Induce regulatory T cells * **High** hygiene levels, **low** pathogen load, absence of helminth infection proposed to: * Skew immunity towards **Th2** * Reduce production of regulatory T cells * Has proved resilient as a theory, but remains somewhat theoretical

_Hygiene hypothesis: Strachan 1989_ * Low hygiene levels, high pathogen load, ... infection proposed to: * Skew immunity from Th2 to Th1 * ... regulatory T cells * High hygiene levels, low pathogen load, absence of ... infection proposed to: * Skew immunity towards Th2 * ... production of regulatory T cells * Has proved resilient as a theory, but remains somewhat theoretical

* Low hygiene levels, high pathogen load, **helminth** infection proposed to: * Skew immunity from Th2 to Th1 * **Induce** regulatory T cells * High hygiene levels, low pathogen load, absence of **helminth** infection proposed to: * Skew immunity towards Th2 * **Reduce** production of regulatory T cells * Has proved resilient as a theory, but remains somewhat theoretical

_Detection of allergen-specific IgE in vivo: skin testing_ * Skin ... testing * Allergen extract applied as ... * ... layers of epidermis punctured with lancet * A wheal with ... response after 15 minutes is positive * Result needs interpretation in clinical context

* Skin **prick** testing * Allergen extract applied as **drops** * **Top** layers of epidermis punctured with lancet * A wheal with **flare** response after **15** minutes is positive * Result needs interpretation in clinical context

In skin prick testing (allergy) a ... with flare response after ... minutes is positive

In skin prick testing (allergy) a **wheal** with flare response after **15** minutes is positive

_Detection of allergen-specific IgE in vitro_ * Performed by radioallergosorbant (RAST) assay a very long time ago * Now usually by ..., but term ‘RAST’ still widely used clinically

* Performed by radioallergosorbant (RAST) assay a very long time ago * Now usually by **ELISA**, but term ‘RAST’ still widely used clinically

_Treatment of allergy: Pure symptom relievers (don’t act on mediators, but act on other pathways that oppose actions of mediators)_

_Treatment of allergy: Pure symptom relievers (don’t act on mediators, but act on other pathways that oppose actions of mediators)_ * Nasal decongestants * eg oxymetazoline * Act on ... adrenoreceptors to cause vasoconstriction * Only for short-term use * ... and systemic * B2 ... * Eg salbutamol * Act on lung B2 adrenoreceptors, cause smooth muscle ... * Epinephrine/Adrenaline * Systemic adrenergic effects oppose vasodilatation and bronchoconstriction

* Nasal decongestants * eg oxymetazoline * Act on **α1** adrenoreceptors to cause vasoconstriction * Only for short-term use * **Topical** and systemic * B2 **agonists** * Eg salbutamol * Act on lung B2 adrenoreceptors, cause smooth muscle **relaxation** * Epinephrine/Adrenaline * Systemic adrenergic effects oppose vasodilatation and bronchoconstriction

_Treatment of allergy: Pure symptom relievers (don’t act on mediators, but act on other pathways that oppose actions of mediators)_ * Nasal decongestants * eg oxymetazoline * Act on α1 adrenoreceptors to cause ... * Only for short-term use * Topical and systemic * B2 agonists * Eg ... * Act on lung B2 adrenoreceptors, cause smooth muscle relaxation * Epinephrine/Adrenaline * Systemic adrenergic effects oppose ... and ...

* Nasal decongestants * eg oxymetazoline * Act on α1 adrenoreceptors to cause **vasoconstriction** * Only for short-term use * Topical and systemic * B2 agonists * Eg **salbutamol** * Act on lung B2 adrenoreceptors, cause smooth muscle relaxation * Epinephrine/Adrenaline * Systemic adrenergic effects oppose **vasodilatation and bronchoconstriction**

_Treatment of allergy: drugs acting on early-phase mediators_

_Mast cell stabilisers_ * Eg sodium cromoglycate * Reduce mast cell ... by unknown mechanism * Not ... absorbed – ... use only * Short ...-... requires frequent dosing * Main benefit is ...-free, but efficacy ...

* Eg sodium cromoglycate * Reduce mast cell **degranulation** by unknown mechanism * Not **orally** absorbed – **topical** use only * Short **half-life** requires frequent dosing * Main benefit is **steroid**-free, but efficacy **very poor**

_H1 Antihistamines_ * Inverse ... at H1 histamine receptor * Best used before ... to allergen * 1st generation eg chlorpheniramine * Considerable ..., drug interactions * 2nd generation eg cerizine, loratidine, desloratidine, fexofenadine * No/ minimal ..., once-daily

* Inverse **agonists** at H1 histamine receptor * Best used before **exposure** to allergen * 1st generation eg chlorpheniramine * Considerable **sedation**, drug interactions * 2nd generation eg cerizine, loratidine, desloratidine, fexofenadine * No/ minimal **sedation**, once-daily

_Leukotriene receptor antagonists_ * Only UK drug is ... * Effective in reducing ... allergic responses, but ... to H1 antihistamines * Unlike anti-histamines, beneficial in ... asthma, which is the main indication for their use

* Only UK drug is **montelukast** * Effective in reducing **early** allergic responses, but **inferior** to H1 antihistamines * Unlike anti-histamines, beneficial in **chronic** asthma, which is the main indication for their use

_Treatment of allergic disease: corticosteroids_ * Steroids reduce immune activation by altering gene ... in numerous cell types, including T cells, B cells and cells of the ... immune system. Their onset of action is ... and they must be taken ...

* Steroids reduce immune activation by altering gene **expression** in numerous cell types, including T cells, B cells and cells of the **innate** immune system. Their onset of action is **delayed** and they must be taken **regularly**

_Corticosteroids - Types_ * Inhaled - eg b..., fluticasone * Nasal - eg b..., mometasone, fluticasone * Skin - h... and opthalmic drops * Topical prep may cause local and even .. side effects * Oral, ... and depot prep available

* Inhaled - eg **beclamathosome**, fluticasone * Nasal - eg **beclamathasone**, mometasone, fluticasone * Skin - **hydrocortisone** and opthalmic drops * Topical prep may cause local and even **systemic** side effects * Oral, **IV** and depot prep available

_Treatment of allergic disease: Omalizumab_ * Omalizumab is a ... ... directed against ..., used for atopic asthma (amongst other things)

* Omalizumab is a **monoclonal antibody** directed against **IgE**, used for atopic asthma (amongst other things)

...lizumab is a monoclonal antibody directed against IgE, used for atopic ... (amongst other things)

**Omalizumab** is a monoclonal antibody directed against IgE, used for atopic **asthma** (amongst other things)

Omalizumab is a monoclonal antibody directed against ...., used for ... asthma (amongst other things)

Omalizumab is a monoclonal antibody directed against **IgE**, used for **atopic** asthma (amongst other things)

_Treatment of allergic disease: allergen-specific immunotherapy_ * Allergen doses administered by ... injection or sub... * Provide ...-term protection * Mainly ... allergy and rhinitis * Multiple immunological effects: * Induce regulatory T cell responses to allergens * Reduce Th... responses * Induce allergen-specific ... antibodies * Reduction in mast cell responsiveness * Reduce allergen-specific IgE levels

* Allergen doses administered by **subcutaneous** injection or **sublingually** * Provide **long**-term protection * Mainly **venom** allergy and rhinitis * Multiple immunological effects: * Induce regulatory T cell responses to allergens * Reduce **Th2** responses * Induce allergen-specific **IgG** antibodies * Reduction in mast cell responsiveness * Reduce allergen-specific IgE levels

_Treatment of allergic disease: allergen-specific immunotherapy_ * Allergen doses administered by subcutaneous injection or sublingually * Provide long-term protection * Mainly venom allergy and ... * Multiple immunological effects: * Induce ... T cell responses to allergens * Reduce Th2 responses * Induce allergen-specific IgG antibodies * Reduction in ... cell responsiveness * Reduce allergen-specific ... levels

* Allergen doses administered by subcutaneous injection or sublingually * Provide long-term protection * Mainly venom allergy and **rhinitis** * Multiple immunological effects: * Induce **regulatory** T cell responses to allergens * Reduce Th2 responses * Induce allergen-specific IgG antibodies * Reduction in **mast** cell responsiveness * Reduce allergen-specific **IgE** levels

_Contact dermatitis vs type 1 allergy_

_Skin prick testing vs patch testing_