Allergy overview - University of Cape Town · Allergy overview Mike Levin Division of Asthma and...

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Allergy overview Mike Levin Division of Asthma and Allergy Department of Paediatrics University of Cape Town Red Cross Hospital

Transcript of Allergy overview - University of Cape Town · Allergy overview Mike Levin Division of Asthma and...

Allergy overview

Mike Levin

Division of Asthma and Allergy

Department of Paediatrics

University of Cape Town

Red Cross Hospital

Adaptive Immune Responses • Adaptive immune responses allow responses against

specific antigens and are essential for normal health

• However, adaptive immune responses can sometimes cause serious disease when elicited to antigens not associated with infectious pathogens

Adaptive immune response

Pathogens Self-antigens Harmless,

environmental antigens

Protection

Hypersensitivity, Allergy

Autoimmunity

Hypersensitivity

• Objectively reproducible symptoms or signs

initiated by exposure to a defined stimulus

at a dose tolerated by normal persons

• No reference to pathological mechanism

Hypersensitivity

• Objectively reproducible symptoms or signs

initiated by exposure to a defined stimulus

at a dose tolerated by normal persons

• No reference to pathological mechanism

Allergy • Exaggerated immune reaction to trigger molecules,

usually benign proteins, called allergens.

• Hypersensitivity reaction - initiated by an immunological mechanism

• Antibody mediated – IgE antibodies

– IgE-mediated allergy

• Cell mediated – Non-IgE mediated allergy

– Allergic inflammation

Atopy

• Personal or familial tendency to produce IgE antibodies in response to low doses of allergens, and is accompanied by typical symptoms of asthma, rhinoconjunctivitis or eczema/dermatitis

• Genetic predisposition to become IgE sensitised to allergens

• IgE sensitisation (IgE in serum or +ve SPT)

Allergen

• Antigen causing allergic disease

• Proteins

• Carbohydrate side chains

• LMW chemicals: Haptens (e.g. isocyanates,

anhydrides)

Allergy

• Allergy is not a disease!

• It is a mechanism that is important in some

diseases all the time, and in others for some

of the time.

Asthma

Drug

reactions

ALLERGY

Food

intolerance Rhinitis

Eczema

Urticaria

Angioedema

Th2 B cell

Allergen

specific

IgE

Allergen

Antigen

presenting

cells

APC

IL-4

Allergen

specific

Th2 cells

Allergen

specific

B cells

Allergen specific T-

and B-cell memory

response

Type I IL-4R

MHC II

T cell receptor

IL-4

Sensitisation Phase

Other

cytokines?

Allergen

(e.g. pollen)

IgE antibody Mast cell

degranulation

Acute

symptoms

of allergy

Histamine

Mast cell

Chronic

symptoms of

allergy Th2 cytokines

and chemokines

Allergen

(e.g. pollen)

Th2

cell

APC

CD4+

Th2 cytokines

and chemokines

Allergen

(e.g. pollen)

Th2

cell

IgE antibody Mast cell

degranulation

Histamine

APC

Type I

IgE mediated

allergy

CD4+

Mast cell

Type IV

Th2

hypersensitivity

Release of IgE

Plasma cell

B lymphocyte

-switch

Allergic Exacerbation

Allergic Inflammation:

eosinophils and lymphocytes

Allergens

Mast cells Basophils

Allergic mediators

IgE Sensitisation and elicitation

IgE

Allergens

FcRI

Over Minutes Lipid mediators: Prostaglandins Leukotrienes

Wheezing Bronchoconstriction

Over Hours Cytokine production: Specifically IL-4, IL-13

Mucus production Eosinophil recruitment

Immediate Release Granule contents: Histamine, PAF, TNF-, Proteases, Heparin

Sneezing Nasal congestion Itchy, runny nose Watery eyes

Early & Late phase IgE reaction

TH0

TH1

TH2

Interferon

Interleukin 2

Cell-mediated immunity

Intracellular pathogens

Autoimmunity

Interleukin 4

Interleukin 5

Interleukin 13

Humoral Immunity

Parasite defense

Allergic Disease

Intracellular

Pathogens

Interleukin 12

Parasites

Allergens

Interleukin 4

JAMA. 1997;278:1845.

Regulatory T-cells

Progression of allergy

• Allergy can progress from one form to another – the march…

• Not all children progress

Progression of allergy

Low risk High risk

Family

history

Neither parent

has allergies

One parent has

allergies

Both parents

have allergies

Chance of

child with

allergies

10 – 15 %

30 – 40 %

70 – 80 %

Low risk High risk

Family

history

Neither parent

has allergies

One parent has

allergies

Both parents

have allergies

Chance of

child with

allergies

10 – 15 %

30 – 40 %

70 – 80 %

• Recommendations

– No dietary restriction in pregnancy

– Oily fish +- omega 3 supplementation. Fruit and vegetables

– Breast feed (No diet restriction) for 4-6 months

– If high risk and cannot BF hydrolysed formulae (not CM, AAF or soy)

– Introduce solids from 4-6 months. No data on later or earlier.

– Avoid exposure to cigarette smoke

– Mixed data on probiotics and prebiotics

– Mixed data on pets &HDM so no environmental interventions

Prevention of allergy

• Secondary prevention

– Rhinitis : Better treatment helps asthma

– Immunotherapy for rhinitis reduces sensitisations and may prevent asthma

– Asthma : Better treatment helps rhinitis

– Food allergy : Treats eczema

– Eczema … May prevent food allergy and onset of asthma

– Drugs ETAC and EPAAC

Prevention of allergy

Allergic Diseases

Allergic Diseases

• Food Hypersensitivity

• Urticaria

• Anaphylaxis

• Eczema

• Rhinitis

• Asthma

• Conjunctivititis

• Drug Hypersensitivity

• Insect sting or bite hypersensitivity

Allergic Diseases

• Food Hypersensitivity

• Urticaria

• Anaphylaxis

• Eczema

• Rhinitis

• Asthma

• Treatment in general

• Prevention

Education

Allergen avoidance

Anti-allergic medicines

Immunotherapy

The Treatment of Allergy

Education

Allergen avoidance

Anti-allergic medicines

Immunotherapy

The Treatment of Allergy

House Dust Mite

Avoidance

Education

Allergen avoidance

Anti-allergic medicines

Immunotherapy

The Treatment of Allergy

Anti-allergic Medicines

Education

Allergen avoidance

Anti-allergic medicines

Immunotherapy

The Treatment of Allergy

Varney, Kay, Durham et al BMJ. 1991

Pollen Counts Symptoms Drug usage

Anti-IgE (omalizumab,Xolair®)

Histamine

Secretory

granule

IgER

Allergen

cross-bridging

Anchored IgE

Circulating IgE

IgE

Anti-IgE

Anti-IgE (omalizumab,Xolair®) for the

treatment of allergy