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Allergy Pathophysiology

Robin J Green

PhD

Department of Paediatrics,

University Pretoria

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What I’m Going To Say! Definitions are important

Describe the pathophysiology of IgE mediated allergy 

Highlight the importance of inflammation Describe some modifiers to this process

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The Hypersensitivity Reactions

Type I: Immediate

Type II: Cytotoxic

Type III: Immune complex

Type IV: Delayed

Gell & Coombs

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Definition

 Allergy = Hypersensitivity

reaction mediated by

immunological mechanisms

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Atopy   ‘Inherited tendency to produce increased amounts

of IgE in response to small quantities of allergen,

and to produce a clinical syndrome (asthma,allergic rhinitis, atopic eczema)’

= Allergy + Clinical disease entity 

Non-atopic conditions with elevated IgE: Bee

 venom hypersensitivity/Drug reactions

JACI 2005

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Hypersensitivity

 AllergicHypersensitivity 

Non-AllergicHypersensitivity 

IgE Mediated Non-IgEMediated

 Atopic Non-Atopic

Helminths,Insect reactions,drug reactions

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Primary Atopic Conditions

 Allergic rhinitis (AR)

Intermittent allergic rhinitis (SAR)

Persistent allergic rhinitis (PAR)

Sinusitis

 Atopic eczema (AE)

 Allergic asthma (AA)

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 Atopic Eczema

Dermatitis (Inflammatory skin

condition)

Eczema Contact

Dermatitis

Atopic Eczema(IgE mediated)

 Non-AtopicEczema

(Non-IgE

mediated)

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Pathophysiology of Allergy:

Type I Hypersensitivity ReactionTH2 = Type 2 helper T cell;IL = Interleukin;GM-CSF = Granulocyte-macrophage

colony –

stimulating factor;IgE = Immunoglobulin E.

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Antigen Re-exposureTH2 = Type 2 helper T cell;IL = Interleukin;

GM-CSF = Granulocyte-macrophage colony –stimulating factor;

IgE = Immunoglobulin E.

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Broad Allergic Cascade - Mediators

IL = Interleukin; TNF-  = Tumor necrosis factor-alpha; RANTES = Regulated on activation, normal T

cell expressed and secreted; VCAM = Vascular cell adhesion molecule; ICAM-1 = Intercellularadhesion molecule-1.

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 Antigen

Dendriticcell

MHC II

 Antigen

T-cellreceptor 

TH2

lymphocyte

IL-4IL-13

IL-5

B lymphocyte

IL-4IL-13

Bone marrow

IL-5EotaxinsRANTES

Plasma cellmaturationIgE switching

+

+

+

+

+

 Antigen

 Antigen

Nasal epithelium

Mast cell

HistamineLTsPGsTryptase

ExudationVasodilation

Sneeze/itch

CNS/peripheralnerves

RhinorrheaMucosal edema

EPR

+

+

+IL-4IL-13

Eosinophils

Basophils

Endothelium

 Adhesion molecules(ICAM-1)

Cellular infiltrationEosinophils: MBP, ECPBasophils: Cytokines

ChemokinesT lymphocytesMacrophages

Chronic Nasal Obstruction

LPR+

+

+RANTES

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Source: Peter J. Barnes, MD

 Asthma Inflammation: Cells and Mediators

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Inflammation

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Source: Peter J. Barnes, MD

 Asthma Inflammation: Cells and Mediators

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CysLTs

Airway

epithelium

Increasedmucus secretion

Decreased mucus

transport

Cationic proteins

(epithelial cell damage)

Increased release

of tachykinins

Sensory C

fibres

Smooth muscle

Contraction and

proliferation

Inflammatory cells

(e.g., mast cells,

eosinophils)

Blood

vessel

Oedema

Adapted from Hay DW et al. Trends Pharmacol Sci 1995;16:304-309

Role of CysLTs in the Airways

18

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Source: Peter J. Barnes, MD

Mechanisms: Asthma Inflammation

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Inflammation

Inflammation

Symptoms

Complications

Signs

f

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Pathophysiology of Atopic Eczema

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THE IMMUNE SYSTEM:

Factors Influencing the Immune system

Malnourished are at a higher risk of

diseases and infection

Mod. Ex improves,

Excess depresses

 Nerve and immune cells

interact

Suppresses immune

cells

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Viruses and Allergy/Asthma

 Atopy

 Asthma

Rhinovirus

RSV

Genes

Influenza

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Rhinovirus and asthma

 Atopy

Decrease inlamda

interferon

Increase in

ICAM - 1

Rhinovi rus 

 Asthma

exacerbations Remodeling

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 Airway Inflammation and Pre-school Asthma

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Thank YouProf Refiloe Masekela

Prof Max Klein

Dr Omolemo Kitchin

Dr Debbie White

Dr Carla Els

Dr Marian Kwofie-Mensah