allergy pathophysiology allsa 2010 (cơ chế 4 type dị ứng)

Allergy Pathophysiology
Robin J Green
PhD
Department of Paediatrics,
University Pretoria


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


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
colony–stimulating 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