Allergy Pathophysiology

Robin J Green
PhD
Department of Paediatrics,
University Pretoria

What Im Going To Say!

Definitions are important

Describe the pathophysiology of IgE mediated allergy

Highlight the importance of inflammation
Describe some modifiers to this process

The Hypersensitivity Reactions

Type I: Immediate
Type II: Cytotoxic
Type III: Immune complex
Type IV: Delayed

Gell & Coombs

Definition
Allergy = Hypersensitivity
reaction mediated by
immunological mechanisms

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

Hypersensitivity
Non-Allergic
Hypersensitivity

Allergic
Hypersensitivity

IgE Mediated

Atopic

Non-IgE
Mediated

Non-Atopic

Helminths,
Insect reactions,
drug reactions

Primary Atopic Conditions

Allergic rhinitis (AR)
Intermittent allergic rhinitis (SAR)
Persistent allergic rhinitis (PAR)

Sinusitis
Atopic eczema (AE)
Allergic asthma (AA)

Atopic Eczema
Dermatitis (Inflammatory skin
condition)

Eczema

Atopic Eczema
(IgE mediated)

Contact
Dermatitis

Non-Atopic
Eczema
(Non-IgE
mediated)

Pathophysiology of Allergy:
Type I Hypersensitivity Reaction
TH2 = Type 2 helper T cell;
IL = Interleukin;
GM-CSF = Granulocyte-macrophage
colonystimulating factor;
IgE = Immunoglobulin E.

THE IMMUNE SYSTEM: How does it function ?

Antibody production (3rd line of defense)
Stages in this process
are:
Antigen detection
Activation of
helper T cells
Antibody
production by B
cells

Antigen Re-exposure
TH2 = Type 2 helper T cell;
IL = Interleukin;
GM-CSF = Granulocyte-macrophage colony
stimulating factor;
IgE = Immunoglobulin E.

Broad Allergic Cascade - Mediators

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

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

Antigen
Antigen

Nasal epithelium

EPR
Dendritic
cell

Antigen

Sneeze/itch
Antigen

MHC II

T-cell
receptor

IL-4
IL-13

T H2
lymphocyte

IL-4
IL-13
IL-5
Eotaxins
RANTES

IL-5

CNS/peripheral
nerves

Histamine
LTs
PGs
Tryptase

IL-4
IL-13

Bone marrow
Basophils

Rhinorrhea
Mucosal edema

Exudation
Vasodilation

Adhesion molecules
(ICAM-1)

LPR
Cellular infiltration
Eosinophils:
MBP, ECP
Basophils:
Cytokines
Chemokines
T lymphocytes
Macrophages

B lymphocyte

+
Plasma cell
maturation
IgE switching

Mast cell

RANTES

Eosinophils

Endothelium

Chronic Nasal Obstruction

Asthma Inflammation: Cells and Mediators

Source: Peter J. Barnes, MD

Inflammation

Asthma Inflammation: Cells and Mediators

Source: Peter J. Barnes, MD

Role of CysLTs in the Airways

Increased
mucus secretion

Decreased mucus
transport

Airway
epithelium

Cationic proteins
(epithelial cell damage)

Increased release
of tachykinins

Blood
vessel

CysLTs
Oedema
Inflammatory cells
(e.g., mast cells,
eosinophils)

Sensory C
fibres
Smooth muscle

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

18

Mechanisms: Asthma Inflammation

Source: Peter J. Barnes, MD

Inflammation
Symptoms

Signs

Inflammation

Complications

Pathophysiology of Atopic Eczema

THE IMMUNE SYSTEM:

Factors Influencing the Immune system
Malnourished are at a higher risk of
diseases and infection

Suppresses immune
cells

Mod. Ex improves,
Excess depresses

Nerve and immune cells

interact

Viruses and Allergy/Asthma

Influenza

Genes

Atopy

Rhinovirus

Asthma
RSV

Rhinovirus and asthma

Rhinovirus

Decrease in
lamda
interferon
Increase in
ICAM - 1

Asthma
exacerbations

Remodeling

Atopy

Airway Inflammation and Pre-school Asthma

Thank You
Prof Refiloe Masekela
Prof Max Klein

Dr Omolemo Kitchin
Dr Debbie White
Dr Carla Els
Dr Marian Kwofie-Mensah