Hypersensitivity Reaction

HYPERSENSITIVITY REACTION

Introduction –

• Immune response is generally a protective process but it may sometimes be injurious to the host.

 Definition –

• The term hypersensitivity reefer's to the injurious consequences in the sensitised host following contact with specific antigen.

• Classification –

• Based on time required for sensitised host to develop clinical reaction on reexposure to the antigen.

• Immediate hypersensitivity (B cell mediated) –

• Anaphylaxis

• Atopy

• Antibody mediated cell damage

• Arthrus phenomenon

• Serum sickness

• Delayed hypersensitivity (T cell mediated) –

• Tuberculin type

• Contact dermatitis

• Comb's & gel classification –

• Type I – (anaphylaxis & atopy)

• Type II – (cytotoxic, Ig G mediated)

• Type III – (immune complex)

• Type IV – (delayed or cell mediated)

Type I [Anaphylaxis & Atopy Reaction] –

• Anaphylaxis – acute, potentially fatal, systemic.

• Atopy – Recurrent, non – fatal, localised.

• Mechanism of anaphylaxis –

• Anaphylaxis occur’s when sensitised individual comes in contact with shocking dose of Ag.

• By any rout such as parenteral, inhalation, or ingestion. But effective rout is parenteral.

• Require interval 2-3 week’s.

• Ig E produced against Ag – attach to surface of mast cells & basophiles.

• Shocking dose of some / related Ag combines with cell bound Ig E Ab on mast cells.

• Ag + Ab complex stimulate mast cells to release mediator that cause clinical manifestation off anaphylaxis.

• Chemical mediator’s –

~ Primary mediator’s –

• Preforme contact of mast cell or basophiles.

• A] Histamine –

• Vasodilatation

• Capillary permeability

• Contraction muscle smooth

• B] Serotonin –

• Vasoconstriction

• Capillary permeability

• Smooth muscle contraction

• C] Eosinophil chemotactic factor of anaphylaxis –

• Released from mast cell

• Strongly chemotactic

~ Secondary mediator’s –

• Which are newly formed by stimulated mast cell.

• A] Slow reacting substance of anaphylaxis (SPSA) more potent than histamine

• B] Prostaglandins

• C] Platelet activating factors (PAF)

Feature of anaphylaxis –

• Occur’s within few second’s to minute.

• Cytotrophic Ig E antibodies are responsible.

• Organ’s which are affected in anaphylaxis are called shock organ.

 Types of anaphylaxis –

• a] Anaphylaxis in vitro. (Schultz – Dale phenomenon)

• tissue from sensitised guinea pig – kept in ringer solution– organ contract’s vigorously on

• addition of specific Ag to bath.

• b] Cutaneous anaphylaxis –

• Shocking dose of Ag introdermaly in sterilized host – anaphylaxis.

 Atopy –

• Typified by hay fever & asthma.

• Atopen’s are pollen grain’s, house dust & food’s.

• Feature’s of atopy –

• Run’s in families.

• Tendency to produce regain (Ig E) Ab’s in usually large amounts.

• Reaction occurs at side of entry of Ag.

• Ex inhalation of pollen’s affect’s lung’s etc.

• It is Ig E mediated hypersensitivity reaction.

• Mechanism of atopy –

• Atopen’s + cell bound Ig E on mast cell’s – release mediator’s – resulting atopy.

 Ex –

• 1] Food allergy – egg, mashroom.

• 2] Dust allergy – pollen’s house dust.

• 3] Drug allergy – e.g. Penicillin.

• Prausnitz – kustner (PK) reaction –

• It was original method for detecting atopy antibody.

• Serum collected from kustner, who had gastrointestinal allergy to certain cooked fish – injected intracutaneously into prausnitz 24 hr’s inject small amount of cooked fish extract into same site minule wheal & flare reaction.

Type II [Cytotoxic Reaction] –

• Cytotoxic reaction is mediated by Ig G Ab’s directly against Ag on surface of cell’s resulting

damage of cell.

• Causing phagocytosis, cytotoxicity by NK cell’s lysis through activation of complement system.

Ex – Autoimmune anemia's & hemolytic disease of newborn.

Type III [Immune Complex] Reaction –

• Characterised by deposition of Ag – Ab complex in tissue.

• Activation of complement & infiltration of polymorphonuclear leucocyte leading to tissue damage.

• Two types.

• a] Arthur's reaction –

• Ag + Ab deposited on wall’s of blood vessel’s – active complement & attract neutrophils at

• local site. Leucocyte thrombi are formed – reduce blood supply & cause tissue necrosis.

• b] Serum sickness –

• Systemic form of type III

• Appear’s following single injection of high concentration of foreign serum.

• Ab to foreign serum high in 7-12 day’s.

• Immune complex get deposited on the endothelial lining of blood vessel’s in various part of body causing inflammatory infiltration.

• Differ from other types in that single injection serves as sensitizing & shocking doses.

• Ex –

• Post streptococci glumerulonephritis.

• Dengue hemorrhagic fever.

• Malaria.

Type IV [Delayed / Cell Mediated] Reaction –

• Cell mediated.

• Can not transferred by lymphocyte of TF.

• Mediated by ‘T’ lymphocytes which on contact with specific Ag – release lymphokines – cause biological effect’s on macrophages, leucocytes & tissue cells.

• Occur’s within 48-72 hr’s

• Two types –

• Tuberculin type.

• Contact dermatitis.

• 1] Tuberculin type –

• Small dose of tuberculin is injected intradermally in an individual sensitised to

• tuberculoprotein by prior infection or immunisation – erythema & swelling occur’s at the site

• of injection within 48-72 hr’s.

• Useful to detect delayed hypersensitivity.

• 2] Contact dermatitis –

• Delayed hypersensitivity may sometimes develop as a result of skin contact with a range of

• sensitising material’s – metal such as nickel, drug’s such as penicillin or other antibiotic’s in

• ointment, simple chemical’s like hair dyes, cosmetic’s & soap’s.

• After absorption through skin, these molecules combiner with skin protein to become

• antigenic – CMI is induced in skin.