HYPERSENSITIVITY

BY

ARIF MOHIDDIN

1ST MDS

DEPARTEMENT OF ORAL PATHOLOGY

CONTENTS :

Introduction Definition of Hypersensitivity Types of Hypersensitivity Diseases caused by the Immune responses Conclusion References

INTRODUCTION :

Immunity : Resistance to disease

Immune System : Collection of cells , Tissues

and Molecules that mediate resistance to

infections.

Immune Responses : Coordinated reactions of these cells and molecules to infections , microbes.

These immune responses serve the important function , host defence as capable of causing tissue injury and disease which include Hypersensitivity Reactions.

DEFINITION :

Refers to a condition in which immune response

results in excessive reactions leading to tissue

damage , disease or even death in the sensitised

Host. The term Hypersensitivity was coined by

VON PIRQUET in 1905.

Hypersensitivity occurs in certain individuals who

have contact with antigen & when exposed to

Second dose of the same antigen , allergy

occurs in them . The initial dose of antigen sensitizes the

immune system by Sensitizing B or T cells. – Sensitizing Dose.

The Second dose of antigen that is responsible for causing allergy is - Shocking Dose.

CLASSIFICATION :

Hypersensitivity reactions are classified into

Two main types .

1] Immediate Hypersensitivity

- Occurs in few minutes to few Hours .

- Antibody mediated.

2] Delayed Hypersensitivty

- Occurs slowly , after 24 hours and

reaches peak after 48 – 72 hours .

- Mediated by T cells.

COOMBS & GEL [ 1963] Classification :

TYPES :

- Type I [Anaphylaxis ] – Antibody Mediated

- Type II [Cytotoxic/Cytolytic] – Ab Mediated

- Type III [ Immune complex ] - Ab Mediated

- TYPE IV [ Delayed Type ] - Cell Mediated

- Type V [ Stimulatory Type] – Ab Mediated

- Type VI [ Antibody dependent CMC]

DISTINGUISHING FEATURES :

Immediate Type

Appears and Recedes Rapidly

Antibody Mediated

Easy but short lived

Delayed Type

Appears slowly in 24-72 hrs and lasts longer.

Cell Mediated

Difficult but long lasting

TYPE – I Hypersensitivity

Immediate Hypersensitivity is a rapid , IgE antibody and Mast cell Mediated vascular and Smooth muscle Reaction .

Often followed by Inflammation.

Occur in individuals on Encounter with certain foreign antigens to which they have been exposed previously.

Type – I Reaction also called Anaphylactic Reaction.

Anaphylaxis - Derived from Greek

- Ana = Against

- Phylaxis = Protection Anaphylaxis term used when the

manifestations of allergic reaction are Severe.

It occurs quickly when a large shocking dose of antigen is introduced after one/ more sensitizing doses.

Features of Anaphylaxis :

Anaphylaxis occurs within a few seconds to

few minutes following shocking dose of Antigen . Cytotrophic IgE antibody is Responsible. Tissues or Organs Which are affected in

anaphylaxis are called Target organs or

shock organs .

Sequence of Events :

First Exposure to ANTIGEN

Antigen activation of T – Helper cells

and Stimulate B- cells

Production of IgE

IgE binds with Fc receptors

of Mast cells

[ Sensitizing dose ]

Repeat exposure to Allergen

Activation of Mast cell

Release of Mediators

Vasoactive amines, Cytokines

Lipid Mediators

- Vascular dilatation - Inflammation

- Smooth muscle

contraction

Activated Mast cells :

Types of Anaphylaxis :

Systemic anaphylaxis :-

Schultz – Dale phenomenon :

- Guinea pigs were given sensitizing dose of

antigen . After some time uterus / ileum was

isolated & kept in Ringer solution .

- Shocking dose of same antigen was added to the

bath , the organ contracted vigorously .

Localised Anaphylaxis :

Applicaion of small dose of antigen on mucosal

surface such as Conjunctiva , Nasal mucosa ,

Respiratory tract Leads to

- Rhinorrhoea

- Conjunctivitis

- Bronchospasm

Eg : Wheal & flare reaction

Angiodema :

Causes :

Foods

Medications

Latex proteins

Idiopathic

Clinical aspects :

Clinical Aspects

Allergic rhinitis, Sinusitis [Hay fever]

Bronchial Asthma

Anaphylaxis

Manifestations

Increased mucus secretion

Smooth muscle contraction & inflammation and tissue injury caused by Late phase.

Fall in BP caused by vascular dilatation & airway obstruction due to laryngeal odema

TREATMENT :

Anaphylaxis

- Epinephrine Bronchial Asthma

- Corticosteroids

Type – II [ Cytotoxic ] Reaction:

Cytotoxic reactions Mediated by IgG or IgM

Directed against antigens on the surface of cells

resulting in Cell Damage . Antibodies bind to an antigen on the cell surface and

cause

- Phagocytosis of the cell through opsonic

or Imune adherence.

- cytotoxicity by Natural Killer Cells

- Lysis through activation of Complement

System

Examples :

- Isoimmune Reaction :

ABO transfusion

Erythroblastosis foetalis

RH Factor Incompatibility :

Type – III [ Immune Complex ] Reaction:

It is Characterized by deposition of Ag – Ab complexes in tissues

Activation of Complement system. Infiltration by polymorphonuclear leucocytes ,

platelets Leading to tissue damage

Mechanism :

When Antigen combines with antibody complexes are formed .

Normally these are removed by monocytes & macrophages.

Inefficient in removing Smaller complexes formed in antigen excess

Those complexes deposited in vascular endothelial surfaces causing immune complex diseases.

Examples :

Arthus Reaction :

- The tissue damage due to Ag – Ab complexes

formed at equivalence or slight antibody

excess.

- Activate complement system and attract

neutrophils at the site.

- leukocyte – platlet thrombi formed

- Reduced blood supply

- Tissue Necrosis.

Serum sickness :

Systemic form of type III hypersensitivity It appears following a single injection of

concentration of foreign serum. Antibodies to serum develop within 7-12 days. Immune complexes deposited o epithelial

lining of blood vessels in various parts of body. Inflammatory infiltration Tissue damge

Type – IV [ Delayed / cell mediated ] :

This reaction is mediated by sensitised T- lymphocytes

On contact with specific antigen , Release

Lymphokines that cause biological effects on

Macrophages, leucocytes and tissue cells . Tissue damaging mediated by T lymphocytes.

Types : Tuberculin type :

- A small amount of tuberculin injected in a

sensidized individual .

- with in 24 -72 hours

- After intra dermal injection of PPD in a

sensitized individual – an Erythema

and induration at the site of injection

Contact Dematitis :

Due to repeated contact with a wide

range of sensitizing materials such as:

- Drugs : Pencillin

- Metals : Nickel , Chromium

- Simple Chemicals : Soaps , Hair dyes

RECURRENT APHTHOUS STOMATITIS :

T – cell mediated Tumour necrosis factor is on of the most

important cytokine implied in the development of new apthous ulcers in patients.

Type – V [ Stimulatory type ] Reaction:

It is a modification of Type – II hypersensitivity

reaction . Antibodies interact with antigens on cell surface

that leads to cell proliferation and differentiation

instead of inhibition / killing . Ag- Ab reaction enhances the activity of affected

cell.

Eg: Graves disease

Type – VI [ ADCC ] Reaction:

It is mediated through natural killer cells.

Target cells coated wth low concentration

of Ab’s are killed by NK cells through an

extra cellular non – phagocytic mechanism.

Mechanism :

- Ag’s after introduction into body attaches to the

target cell & induce Ab production.- These Ab combine with specific Ag’s form

complexes on target cells.- NK cells combines with these complexes via

Fc fragment of Ab & causes lysis of Target ells.

CONCLUSION :

Knowledge regarding basic part of immumnology and related part like hypersensitivity provides us an insight to understand etiopathogenisis occuring in certain disease conditions to have better diagnosis , prognosis ..

References:

Basic immunology – Abul. K.ABBAS

Second Edition A Text Book of Medical Microbiology

- Dr. Imtiyaz WANI Robbins Basic Pathology – Ninth Edition