HYPERSENSITIVITY REACTION(TYPE I and TYPE II)

BY: JEGANATHAN CDEPARTMENT OF BIOMEDICAL SCIENCE

E.Mail : jeganathanbms@gmail.comCell.no: 9626307988

INTRODUCTION

• Hypersensitivity (also called hypersensitivity reaction or intolerance) is a set of undesirable reactions produced by the normal immune system, including allergies and autoimmunity.

• Inflammatory response can have deleterious effects ,resulting in significant tissue damage or even death. this appropriate immune response is termed hypersensitivity or allergy.

• Hypersensitivity reaction may develop in the course of either humoral or cell mediated responses

TYPES

• IgE mediated (type I) hypersensitivity • Antibody-mediated cytoxic (type II)

hypersensitivity• Immune complex –mediated (type III)

hypersensitivity• Delayed- type hypersensitivity (DTH)

IgE mediated hypersensitivity

• Type 1 reaction also called as immediate hypersensitivity reaction

• It is induced by certain types of antigen ,referred to as allergens

• The allergen induces a humoral antibody response

• IgE binds with high affinity to Fc receptors on the surface of tissue mast and basophils

• Such IgE- coated mast cells and basophils are sensitized

Continuous………

• A later exposure to the same allergen cross-links the membrane- bound IgE on sensitized mast cells and basophils, causing degranulation of these cells

• The pharmacologically active mediators released from the granules act on the surrounding tissues

COMMON ALLERGEN ASSOCIATED WITH TYPE 1 REACTION

• Proteins-foreign serum , vaccines• Plant pollens-rye grass ,ragweed, timothy

grass,birch trees• Drugs- penicillin, sulfonamides, local

anesthetics,salicylates• Foods-nuts, seafood,eggs,peas,beans,milk• Insect products-bee venom, wasp venom,ant

venom,cockroach calyx,dust mites• Mold spores , animal hair and dander

MECHANISM OF ACTION

• Receptor cross linkage • Intracellular events leading to mast-cell

degranulation

RECEPTOR CROSSLINKAGE

RECEPTOR CROSS LINKAGE

Mechanism of type I allergy: Calcium influx to mast cell

NON IgE ANTIBODY-RELATED INITIATORS OF TYPE I HYPERSENSITIVITY

Complement Activation Products: C3a, C4a, C5a "Anaphylotoxins"

Various Drugs: ACTH, Codeine, Morphine, Penicillin

MEDIATORS

Mediators of Type I Hypersensitivity:Stored in Mast Cell Granules

Histamine, Heparin and Serotonin Increased vascular

permeability; Smooth Muscle Contraction

Chemotactic Factors forEosinophils and Neutrophils Attract Eosinophils & Neutrophils

Proteases Degrade Basement membranes of blood vessels; Activate bronchial mucous secretions;

Activate Complement

Secondary Mediators of Type I Hypersensitivity:Synthesized and Released After Mast Cell Activation

Platelet Activating Factor Platelet Aggregation& Degranulation; Smooth muscle contraction

Prostaglandins Vasodilation; Smooth muscle contraction

Leukotrienes (SRS-A)* Increased vascular permeability; Pulmonary smooth muscle contraction

(*SRS-A : Slow Reacting Substance of Anaphylaxis)

Bradykinin Increased vascular permeability; Smooth muscle contraction

Cytokines: Systemic Anaphylaxis; (IL1 & TNF-a; Others*) Altered Cell adhesion* See Slide 42

Detection of type I hypersensitivity

• Radioimmunosorbent test (RIST)- Quantify Nano gram amounts of total serum IgE

• Radioallergosorbent test (RAST)-Quantify Nano gram amounts of serum IgE specific for a particular allergen

To Treat Type I Immediate Hypersensitivity Based on the Underlying Mechanisms

• Block Effects of Primary Mediators on Target Cells (e.g. respiratory smooth muscles or vascular endothelium) : Antihistamines; Cortisone

• Block Calcium Ion Influx: Cromolyn• Block the Effects of Calcium Ion Influx

a. Keep cyclic AMP (cAMP) from Falling Theophylline

• Increase production of cAMP: Adrenaline(epinephrine)

ANTIBODY – MEDIATED CYTOTOXIC HYPERSENSITIVITY

• Type II hypersensitivity reaction involve antibody- mediated destruction of cells

• This type is best exemplified by blood – transfusion reactions, in which host antibodies react with foreign antigens on the incompatible transfused blood cells and mediate destruction of these cells

Type II Hypersensitivity

• Results when Ig or IgM bind to cell surface Ag’s– Activating Complement– Binding Fc receptors on Tc cells promoting ADCC

• Both processes result in lysis of the Ab-coated cell

• Clinical examples of Type II responses include:– Certain autoimmune diseases where Ab’s produced

vs membrane Ag’s• Grave’s Disease – Ab’s produced vs thyroid hormone

receptor• Myasthenia Gravis – Ab’s produced vs acetylcholine

receptors• Autoimmune hemolytic anemia – Ab’s produced vs RBC

membrane Ag’s– Hemolytic Disease of the Newborn – Hyperacute graft rejection• Blood Transfusion • Graft rejection

Type II Hypersensitivity:

Produced by mismatched blood types

Destroys foreign RBC by complement-mediated lysis triggered by IgG

Produces fever, intravascular clots, lower back pain, Hgb in urine

Free Hgb produced has 2 fates:passes to the kidneys – hemoglobinuriaBreaks down to bilirubin. Can be toxic

Type II Hypersensitivity: Hemolytic Disease of the Newborn

• Occurs via maternal IgG Ab’s crossing the placenta• In severe cases causes erythroblastosis fetalis– Most commonly develops in Rh- mother with Rh+ fetus– Exposure to Rh+ fetal RBC’s stimulates prod of

memory/plasma– Activation of memory cells in subsequent pregnancy IgG

Ab’s which can cross the placenta– mild-severe hemolytic anemia ensues along with bilirubin

which affects the brain/CNS

• Treatment centers on anti-Rh antibodies (Rhogam)• Mothers can be tested for anti-Rh antibodies to

check for a rise in titer• Isolated fetal RBC’s can be checked for anti-Rh IgG w/

Coombs test

Hemolytic Disease of the Newborn

Drug-induced hemolytic anemia

• Drugs such as aspirin and antibiotics can bind to the surfaces of RBC’s

• These interactions act similar to hapten-carrier conj.

• Such complexes can trigger Ab-mediated cell lysis by complement activation

REFERRENCE

• Kuby immunology- chapter 16th fourth edition ,pp 397- 415