HYPERSENSITIVITY REACTIONS

HYPERSENSITIVITY REACTIONS

Innocous materials can cause hypersensitivity in certain

individuals

leading to unwanted inflammationdamaged cells and tissues

Non-proper reaction of the immune system to foreign substances

Mainly harmless substances – after second or multiple exposure

An overview of hypersensitivity reactions

Type I. „immediate”

Type II. Type III. Type IV.„late”

Antibody mediated T cell mediated

TYPES OF ANTIBODY MEDIATED HYPERSENSITIVITY REACTIONS

FcRIα)

TYPE I HYPERSENSITIVITY REACTION

ALLERGY

SENSITISATION PROCESS

IgE

Fc RIea

bg

foszfatidil-kolin

PGD2

PGD2

PAF

LTC4

PIP2

IP3

DAG

Ca2+Ca2+

Ca2+foszfolipid

PKC

LTC4

LTD4LTE4

LYSO-PC arachidonsav

szekretorosgranulum

mediátorokcitokinekIL-3, IL-4,IL-5, IL-6

TNFa

endoplazmásretikulum

PI-PLCg

Ca2+

Ca2+

szekréció

MAP-kináz

proteinek(miozin-

könnyűlánc)foszforilációja

PLA2

ciklooxigenáz

5-lipoxigenáz

ITAM

ITAM

ITAM

ITAM

ITA

M

ITA

M

citokin génektranszkripciója

SykLyn

NFATAP-1 NF- Bk

MAST CELL RESPONSE TO SURFACE FcRεI CROSSLINKING

EARLY MEDIATORS

Biogenic amins – histamin

Enzymes – triptase, chymase, carboxypeptidase

LATE MEDIATORS

The effect of mast cell degranulation varies with the tissue exposed to allergen

Systemic anaphylaxis is caused by allergens that reach the blood stream

Types of IgE-derived allergic responses

SYNDROME ALLERGENS ROUTE OF ENTRY RESPONSE

systemic anaphylaxis

drugsanti-serum

peanuts

intravenous(either directly or

after rapid absorption)

edema, increased vascular permeabilitytracheal occlusion

circulatory collapse, death

acuteurticaria

bug biteallergy test

subcutan local increase in blood flow and vascular

permeability

allergicrhinitis

pollendust mite

drops

inhaled irritation and edema of nasal mucosa

airway inflammation

asthma animal furpollen

dust mite drops

inhaled bronchial constriction, increased mucus

production

food allergy nut, peanuts,fish, shellfish

milk, eggs

oral vomiting, diarrheapruritis (itching)urticaria (hives)

anaphylaxia (rare)

Mast cell degranulation, allergic reaction in the skin of

a sensibilized individual

Prick test

ImmunoCAPSpecific IgE Blood Test

TYPE II HYPERSENSITIVITY

IgG type antibodies bound to cell surface or tissue antigens

• cells expressing the antigen become sensitive to complement mediated lysis or to opsonized phagocytosis

• frustrated phagocytosis tissue damage

• the antibody inhibits or stimulates target cell function no tissue damage (e.g. M. gravis – receptor-blocking antibodies)

MECHANISMS OF TYPE II HYPERSENSITIVITY REACTIONS

Killing of target cell by effector-macrophage orNK-cell

Killing of targetcell by complement-mediated lysis

complement activation

IgG

IgG

Receptor-specific autoantibodyinterferes withsignal transduction

NKMf

C '

ADCC

DEVELOPMENT OF DRUG SENSITIVITY I.

DEVELOPMENT OF DRUG SENSITIVITY II.

The tissue, which can not be

phagocytosed, is damaged

Absorbed antigen (drug)

FcR

C3R

C3b C3b

C3b

C3b C3b C3b

FRUSTRATED PHAGOCYTOSIS MEDIATED BY IgG TYPE ANTIBODIES

Binding Opsonization Internalization Enzyme release

Opsonized surface Binding Frustrated Enzyme release phagocytosis

Examples - Type II hypersensitivity

Newborn haemolytic anaemiaTransfusion reaction

Drug-derived • Haemolitic anaemia• Thrombocytopenia• Agranulocytosis

• Penicillin-based antibiotics• Anti-arithmic quinidine

TYPE III HYPERSENSITIVITY

Antibodies binding to soluble antigensforming small circulating immune complexes

which are deposited in various tissues

Depends on:Size of immune complexes

Antigen-antibody ratio Affinity of antibodyIsotype of antibody

THE PROCESS OF TISSUE DAMAGE CAUSED BY IMMUNE COMPLEXES

Immune complexes activate the complement system, neutrophils, basophils and thrombocytes

Blood vessel wall

permeability

Frustrated phagocytosis

Antig e n

Antib o d y

Va so a c tivea m ine s

Ba so p hilg ra nulo c yte

Thro m b o c yte s

PM NC he m o ta xis

Im m une c o m p le x

C om p le m e nt-a c tiva tion(C 3a , C 5a )

De p ositio n

End othe liumBa sa l m e m b ra neVe sse l wa ll

C '

C '

Sypmptpomes caused by type III hypersensitivity reactions depend on the site of immunecomplex deposition

Arthus-reaction• Localized Type III hypersensitivity • Local vasculitis develops as a result of immune complex deposition • Inhaled antigens (fungi, animal feces) may induce similar reaction in

the lung• IgG type antibody • ‘Farmer lung’ and ‘piegeon breeder lung’

TYPE IV HYPERSENSITIVITY REACTION

T CELL MEDIATED PROCESS

MACROPHAGES ARE INVOLVED

Type IV hypersensitivity reaction

Chemokines, cytokines,cytotoxins

Delayed-type (TYPE IV) HypersensitivityDelayed-type (TYPE IV) Hypersensitivity

Delayed-type (Type IV) HypersensitivityDelayed-type (Type IV) Hypersensitivity

Delayed-type hypersensitivity (DTH) (e.g., tuberculin skin test)

TH1 from a previous immunization (memory)

Tuberculin skin test

Ag = antigen

Mycobacterium protein (PPD) Introduction of Ag

Chemical Mediators of DTH

*a contact-sensitizing agent is usually a small molecule that penetrates the skin then binds to self-proteins, making them “look” foreign

Contact Dermatitis

DTH as a result of a contact-sensitizing agent*

Poison ivy Anacardiaceae (family), Toxicodendron (genus)Toxicodendron radicans or Rhus toxicodendron