Hypersensitivity

Hypersensitivity

Mohammad Mukhit Kazi Lecturer SDCH Pune

ObjectivesTo know difference between immunity and

hypersensitivityTo know different types of hypersensitivityTo know mechanisms involved in

hypersensitivity


IntroductionImmunity

A protective processHelps body to overcome infectionsSpecific response to antigens

Immune response – sometime injurious to host

A damage to the host, mediated by preexisting immunity to self or foreign antigen.


Definition of hypersensitivityThe injurious consequences in the sensitized host,

following contact with the specific antigen.

For induction of hypersensitivity reactions the host should have had contact with the antigen (allergen)

Initial contact sensitizes the immune system, leading to the priming of the appropriate B or T lymphocytes this is known as sensitizing or priming dose

Subsequent contact with the allergen causes manifestations of hypersensitivity as shocking dose.


Difference between Immunity and HypersensitivityFocus is on antigen and what happens to it

Antigen are of little concern or often innocuous or bland substances such as serum proteins or pollen

e.g. killing of bacterium or neutralization of toxin

It is concerned with what happens to the host as a result of the immune reaction


Musts for Hypersensitivity

Contact with allergen

Sensitizing/priming dose

Induction of AMI/CMI

Shocking dose


AllergyOriginally used by von Pirquet means

An altered state of reactivity to an antigen and included both types of immune responses protective as well as injurious

Also referred as all immune processes harmful to the host such as hypersensitivity and autoimmunity

Commonly used as hypersensitivity


Classification of Hypersensitivity reactionsI. Immediate hypersensitivity (B cell or Ab

mediated) Anaphylaxis

AtopyAntibody mediated cell damageArthus phenomenonSerum sickenss

II. Delayed hypersensitivity (T cell mediated)

Infection (tuberculin) typecontact dermatitis type


Immediate hypersensitivity

Delayed Hypersensitivity

1. Appears and recedes rapidly

1. Appears slowly, lasts longer

2. Induced by antigen or haptens by any route

2. Antigen or hapten intradermally or with Freund’s adjuvant or by skin contact

3. Circulating antibodies present and responsible for reaction; (Ab mediated reaction)

3. Circulating Abs may be absent and not responsible for reaction; cell mediated reaction

4. Passive transfer possible with serum

4. Cannot be transferred with serum; but possible with T cells or transfer factor

5. Desensitization easy but short lived

5. Difficult, but long lasting


Coombs and Gell (1963) classified hypersensitivity reactions into 4 types based on different mechanisms of pathogenesis

Type I (Anaphylactic, IgE or reagin dependent)

Type II ( cytotoxic or cell stimulating)

Type III ( Immune complexes or toxic complex disease)

Type IV ( Delayed or cell mediated hypersensitivity)


A = Type I - Anaphylaxis Reaction

C = Type II - Cytotoxic Mediated Hypersensitivity Reaction

I = Type III - Immune Complex Mediated Hypersensitivity Reaction

D = Type IV - Delayed Hypersensitivity Or Cell Mediated Hypersensitivity Reaction


Type I Reactions (IgE dependent)Occurs in two forms

The acute : potentially fatal, systemic form called anaphylaxis

The chronic or recurrent : Non fatal, typically localized form called atopy


Type-I hypersensitivityType-I hypersensitivity

The common allergy


AnaphylaxisClassical immediate hypersensitivity

reactionAna = withoutPhylaxis = protection

Coined by Richet (1902)Experiment on Dog

Theobald’s smith (1902)Similar phenomenon in guinea pig

Ehrlich named this ‘Theobald Smith phenomenon’


Type I Reactions

Humans –Itching of scalp & tongue,

flushing of skin, difficulty in breathing, nausea, vomiting, diarrhea, acute hypotension, loss of consciousness, death (rare)

Causes Serum therapy,

antibiotics, insect stingsTreatment

Adrenalin 0.5 ml (1 in 1000 solution) SC/IM repeated up to 2 ml in 15 min


Sensitization is most effective given parenterally

But may occur by any routeMinute doses can sensitize the hostAntigens and haptens can induce anaphylaxisThere should be interval of 2-4 weeks

between sensitizing dose and shocking doseShocking dose more effective when given IVIt should be identical to sensitizing dose


The clinical effects are due to smooth muscle contraction and increased vascular permeability

There is also edema, decreased coagulability of blood, fall in BP and temp. leucopenia and thrombocytopenia

Guinea pigs are more susceptible and rats are resistant

Rabbits, dogs and humans are intermediate susceptible


In human beings fatal anaphylaxis fortunately rare

Signs and symptoms begin with itching of the scalp and tongue, flushing of the skin over whole body and difficult in breathing due to bronchial spasm

There may be nausea, vomiting, abdominal pain and diarrhea, sometime blood in stool

Acute hypotension, loss of consciousness & death follows


Insect stings cause anaphylaxis in human beings

Prompt treatment with adrenalin is life saving0.5 ml of a 1 in 1000 solution SC or IMRepeat dose to total 1 ml over 15 minutes if

necessaryCutaneous anaphylaxis

Local wheal and flare response after Ag is administered intradermally

Wheal – pale central areaFlare – hyperemia and erythema


SDC&H

a congestion of the blood, occurring in any part of the body

Passive cutaneous anaphylaxis (PCA)Developed by Ovary (1952)For detection of Abs e.g. IgG Ab

Anaphylaxis in vitroSchultz – Dale phenomenon : Isolated tissues from

sensitized guinea pig held in Ringers solutions will contract vigorously


Mediators for Anaphylaxis

Primary mediators

Histamine : imp vasoactive amine formed by decarboxylation of histidine found in mast cells, basophils and platelets

Released into skin stimulates nerves producing burning and itching sensations

Causes vasodilatation and hyperemia, edema by increasing capillary permiability


Induces smooth muscle contraction and stimulates

Serotonin

Decarboxylation of tryptophan found in intestinal mucosa, brain tissue and platelts

Causes smooth muscle contraction

Increased capillary permeability and vasoconstriction

Chemotactic factors

Eosinophil chemitactic factors are acidic tetrapeptides released from mast cell granules

Strongly chemotactic


Secondary mediators

Prostaglandins and leukotrienes Formed from disrupted cell membrane of mast cells & other

leucocytes They are powerful bronchoconstrictors Prostaglandins also affect secretion by mucous glands, platelet

adhesion, permeability & dilatation of capillaries and the pain threshold

Platelet activating factor Low molecular weight lipid causes aggregation of platelets and release

vasoactive amines

Other mediators of anaphylaxisAnaphylatoxin released by complement activation and

bradykinin


Anaphylactoid reaction

Intravenous injection of peptone, trypsin provokes a clinical reaction resembling anaphylactic shock termed as anaphylactoid reaction

Resemblance is due to same chemicals participating in the reaction

It has no immunologic basis

Non specific mechanism


Atopy

Introduced by Coca (1923)Naturally occurring : hay fever and asthmaAntigens are inhalant or ingestantsDifficult to induce artificiallyGenetically determined probably linked to MHC

genotypesProduce large quantity of IgE antibodiesBottle fed infants tend to develop atopy in later life IgE differs from other immunoglobulin in many waysClinical expression depends portal of entry

Conjunctivitis, rhinitis, gastrointestinal symptoms, dermatitis


1. Cannot be demonstrated in conventional serological reactions

2. Commonly occur in humans not easy in experimental animals

3. IgE is homocytotropic ie species specific

4. Heat sensitive and is inactivated at 56oc in 2 – 4 hours.

5. Does not pass through placenta


Type II Reaction: Cytolytic and CytotoxicInvolve a combination of IgG antibodies with

antigenic determinant on the surface of cellsLeading o cytotoxic or cytolytic effectsLysis of RBCs by antiRBCS antibodies


Type III Reactions: Immune complexes Diseases

Arthus reactionArthus in 1903 observed after repeated injection

of normal horse serum in rabbits subcutaneously develops edema, indurations and hemorrhagic necrosis

Tissue damage is due to antigen – antibody precipitates causing complement activation and release of inflammatory molecules

This leads to increased vascular permeability and infiltration of the site with neutrophils

Leukocyte platelet thrombi are formed that reduces the blood supply and lead to tissue necrosis


Arthus reactionArthus reaction

Arthus reactionType-III

Wheal & flare reactionType-I


• Serum Sickness systemic form of type III hypersensitivityDescribed by von Pirquet 1905Appeared 7 – 12 days following a single injection of

high concentration of foreign serum such as diphtheria antitoxin

Clinical syndrome consists of Fever Lymphadenopathy Splenomegaly Arthritis Glomerulonephritis Endocarditis Vasculitis Urticarial rashes Abdominal pain Nausea Vomiting

Pathogenesis is the formation immune complex get depositied on inner lining of blood vessels in various parts of body causing inflammatory infiltration


Serum sicknessSerum sickness


Depletion of complement Disease is self limitedSingle injection can serve both as the

sensitizing dose and the shocking doseImmune complexes occurs in many diseases

including bacterial, viral and parasitic infections, disseminated malignancies and autoimmune conditions


Type IV Reactions: Delayed hypersensitivity

Provoked by intra cellular parasites or haptensReaction due to sensitized T cells which on

contact with specific antigen releases cytokines that causes biological effects

Cannot be transferred passivelyBut can be transferred by lymphocytesTwo types

TuberculinContact dermatitis type


Tuberculin typeWhen small dose of tuberculin is injected

intradermally in an individual sensitized to tuberculoprotein by prior infection or immunization an indurated inflammatory reaction develops at the site within 48 – 72 hours

In unsensitized individuals no responseUseful indication of the state of DH to the

bacilli


Contact dermatitis typeDue to variety of chemicals, metals, dyesContact dermatitis is an inflammation of

the skin caused by direct contact with an irritating or allergy-causing substance (irritant or allergen). Reactions may vary in the same person over time. A history of any type of allergies increases the risk for this condition.


Contact dermatitis reactionContact dermatitis reaction


Allergic Contact Dermatitis Response to Poison Ivy Hapten


Type-Type-

IVIV

Type-IIIType-IIIType-IIType-IIType-Type-

II

characteristcharacterist

icic

Comparison of hypersensitivity reactionsComparison of hypersensitivity reactions

TB test, TB test, poison ivy, poison ivy, granulomagranuloma

farmers’ farmers’ lung, lung, SLESLE

pemphiguspemphigus, , GoodpastuGoodpasturere

hay hay fever, fever, asthmaasthma

examplesexamples

antibody IgE IgG, IgM IgG, IgM none

antigen exogenous cell surface intracellularsoluble

response time

15-30 min. Min.-hrs 3-8 hours 48-72 hoursor longer

appearance Wheal & flare

Lysis & necrosis

Erythema & edema

Erythema & induration

baso- and eosinophils

Ab and complement

histology PMN andcomplement

Monocytes & lymphocytes

T-cellsantibodyantibodyantibodytransfer with


AutoimmunitySelf antigens are not immunogenic

Autoimmunity is a condition in which structural or functional damage is produced by the action of immunologically competent cells or antibodies against the normal components of the body.

Autoimmunity literally means – protection


Mechanism of autoimmune diseasesCells undergo antigenic alteration due to

physical, chemical or biological influencesThis results in immune responsePhysical agents – irradiation Chemicals – drugsBiological – infectious agents such as

viruses


Classification of Autoimmune diseasesHemolytic autoimmune disease

- Autoimmune hemolytic anemias- Autoimmune thrombocytopenia- Autoimmune leucopenia


Localized autoimmune diseases- Hashimoto’ disease (enlargement of thyroids)- Grave’s disease (Abs to thyroglobulin)- Addision’s disease (lymphocyte infiltration in

adrenal glands)- Autoimmune orchitis - Myasthenia gravis (malfunction of myoneural

junction)- Autoimmune disease of eye- Pernicius anemia- Autoimmune disease of nervous system- Autoimmune disease of skin


Systemic autoimmune diseaseSystemic lupus erythematosusRheumatoid arthritisPolyarteritis nodosaSjogran’s sundrome


Hypersensitivity

Health & Medicine

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