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

Allergy = Hypersensitivity reaction mediated by immunological mechanisms...  ‘Inherited tendency to produce increased amounts of IgE in response to small quantities of allergen, and

What I’m Going To Say!

The Hypersensitivity Reactions

Gell & Coombs

Allergy = Hypersensitivity

reaction mediated by

immunological mechanisms

 ‘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

Allergic Hypersensitivity

Non-Allergic Hypersensitivity

Mediated

Helminths, Insect reactions, drug reactions

Primary Atopic Conditions

 Intermittent allergic rhinitis (SAR)

 Persistent allergic rhinitis (PAR)

(Non-IgE mediated)

Pathophysiology of Allergy:

Type I Hypersensitivity Reaction

T H 2 = 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

T H 2 = 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.

Dendriticcell

Bone marrow

IL-5EotaxinsRANTES

PGsTryptase

ExudationVasodilation

Sneeze/itch

CNS/peripheralnerves

RhinorrheaMucosal edema

Eosinophils

Basophils

Endothelium

Adhesion molecules(ICAM-1) Cellular infiltrationEosinophils: MBP, ECP

Basophils: Cytokines

Chemokines

T lymphocytesMacrophages

Chronic Nasal Obstruction

LPR +

+

+

RANTES

Source: Peter J Barnes, MD

Asthma Inflammation: Cells and Mediators

Inflammation

Source: Peter J Barnes, MD

Asthma Inflammation: Cells and Mediators

Airway

epithelium

Increased mucus 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

Source: Peter J Barnes, MD

Mechanisms: Asthma Inflammation

Inflammation

Symptoms

Complications Signs

Pathophysiology of Atopic Eczema

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

Viruses and Allergy/Asthma

Atopy Asthma

Rhinovirus

RSV

Genes

Influenza

Rhinovirus and asthma

Atopy

Decrease in lamda

interferon

Increase in ICAM - 1

Rhinovirus

Asthma

Airway Inflammation and Pre-school Asthma

Thank You