HYPERSENSITIVITY

chalee

Outline

History
Definition
Basic Concepts
Types of Hypersensitivity
> Characteristics
> Components and Cells
> Process and Mechanism
> Common Diseases

History

Allergies Greek = altered reactivity

1906 von Pirquet coined term:

hypersensitivity

In 1968 Coombs & Gell defined the 4

types of hypersensitivity

Hypersensitivity reactions
> over reaction of the immune system to
harmless environmental antigens
> are harmful antigen-specific immune

responses , occur when an individual who

has been primed by an innocuous antigen
subsequently encounters the same antigen ,
produce tissue injury and dysfunction.

Allergen

the antigens that give rise to

immediate hypersensitivity

Atopy

the genetic predisposition to

synthesize inappropriate levels of IgE
specific for external allergens

Type I
IMMEDIATE HYPERSENSITIVITY

Immediate means seconds to minutes

Immediate Allergic Reactions, which may
lead to anaphylaxis, shock, edema,
dyspnea death
1) Allergen exposure
2) IMMEDIATE phase: MAST cell
DEgranulation, vasodilatation, vascular
leakage, smooth muscle (broncho)-spasm
3) LATE phase (hours, days): Eosinophils,
PMNs, T-Cells

Mechanism of type I hypersensitivity

Allergen

Primary

Individual

Generation

IgE
Adhesion

Secondary

IgE binds to the FcRI on mast cell and basophil

Allergen binds to the IgE on primed target cell
Crosslikage of FcRI

Degranulate and release the biological mediators

Preformed granule mediators New generated mediators
Histamine

Bradykinin Leukotrienes

PAF

Prostaglandin D2

e capillaries,increase permeability, increase mucus secretion, contract smooth m

Systemic
anaphylaxis

Skin

Respiratory tract

Digestive tract

TYPE II HYPERSENSITIVITY
ANTIBODY MEDIATED IMMUNITY

Antibodies attach to cell surfaces

OPSONIZATION
PHAGOCYTOSIS
COMPLEMENT FIXATION (cascade of C1q,

C1r, C1s, C2,

C3, C4, C5.. )

LYSIS (destruction of cells by rupturing or

breaking of the cell membrane)

TYPE II DISEASES

Autoimmune Hemolytic Anemia, AHA

Idiopathic Thrombocytopenic Purpura,
ITP
Goodpasture Syndrome (Nephritis and
Lung hemorrhage)
Rheumatic Fever
Myasthenia Gravis
Graves Disease
Pernicious Anemia, PA

Antigen or hapten on cell

Antibody (IgG, IgM)

Activate complement
Opsonic phagocytosis NK , phagocyte

Lyse target cell

Destroy target cell

Stimulate / block

ADCC

Change the function ofTarget cell

Target cell injury

Mechanism of Type II hypersensitivity

TYPE III HYPERSENSITIVITY

IMMUNE COMPLEX MEDIATED

Antigen/Antibody Complexes
Where do they go?

Kidney (Glomerular Basement Membrane)

Blood Vessels
Skin
Joints

Common Type III Diseases- SLE (Lupus),

Poly(Peri)arteritis Nodosa,
Poststreptococcal Glomerulonephritis,
Arthus reaction (hrs), Serum sickness
(days)

Soluble antigen

Body

Antibody

Immune complex

Small molecular soluble

intermediate molecular soluble Large molecular insoluble
Immune complex
Immune complex
Immune complex

Deposit on the basement of capillaries

Eliminate by phogacytosis
Combine and activate complement system
Basophils and mast cells

C3a,C5a,C3b

Platelets

Infiltration of neutrophils

Blood Clotting Mechanisms

Release of vasoactive amine Phagocytose complex
Release of vasoactive ami
Aggregation of platlets

Release the enzymes in lysosome

ncrease vascular permeability
ThrombusIncrease vascular permeabil
Edema

Tissue injury

Bleeding

Edema

Local or systemic immune complex diseases

TYPE IV HYPERSENSITIVITY CELLMEDIATED (T-CELL) DELAYED

HYPERSENSITIVITY

Tuberculin Skin Reaction

DIRECT ANTIGENCELL CONTACT

GRANULOMA FORMATION
CONTACT DERMATITIS

Induce

Antigen

T cell
(CD4+,CD8+)

CD4+Release
T cell

Secondary
contact

Primed T cell

CD8+
T cell

Cytokines
IL-2
TNF-
INF-
TF
MCF
MIF
MAF
SRF

Infiltration of
monocyte and M
Proliferation of T cell
Exudation and edema
Cytotoxicity

Directly kill target cells

Inflammation characterized by infiltration of M , monocyte,

And tissue injury

Mechanism of type IV hypersensitivity

Some Parasites that can cause

Hypersensitivity Reactions

Ascaris

Onchocerca

Toxoplasma

Enterobious
Enterobious

Plasmodium

Trichuris

Hookworm

Schistosome

Trypanosoma

Leishmania

Taenia

Wuchereria

Soluble antigen

Body

Antibody

Immune complex

Small molecular soluble

intermediate molecular soluble Large molecular insoluble
Immune complex
Immune complex
Immune complex

Deposit on the basement of capillaries

Eliminate by phogacytosis
Combine and activate complement system
Basophils and mast cells

C3a,C5a,C3b

Platelets

Infiltration of neutrophils

Blood Clotting Mechanisms

Release of vasoactive amine Phagocytose complex
Release of vasoactive ami
Aggregation of platlets

Release the enzymes in lysosome

ncrease vascular permeability
ThrombusIncrease vascular permeabil
Edema

Tissue injury

Bleeding

Edema

Local or systemic immune complex diseases