Allergy and Hypersensitivity Zahaib Quadri MD Department of physiology Dow medical college, DUHS.

Allergy and HypersensitivityAllergy and Hypersensitivity

Zahaib Quadri MD

Department of physiology

Dow medical college , DUHS

Important definitionsImportant definitions

Hypersensitivity reactions Are harmful antigen-specific immune responses ,

occur when an individual who has been primed by an innocuous antigen subsequently encounters the same antigen , produce tissue injury and dysfuntion.

Allergen: The antigens that give rise to immediate

hypersensitivityAtopy： The genetic predisposition to synthesize

inappropriate levels of IgE specific for external allergens

Types of HypersensitivityTypes of Hypersensitivity

1. Type I Hypersensitivity2. Type II Hypersensitivity3. Type III Hypersensitivity4. Type IV Hypersensitivity5. Type V Hypersensitivity

Type I HypersensitivityType I Hypersensitivity(Anaphylactic) (Anaphylactic)

Reactions/AllergyReactions/Allergy Occur within minutes of exposure to Occur within minutes of exposure to

antigenantigen Antigens combine with IgE antibodiesAntigens combine with IgE antibodies IgE binds to mast cells and basophils, IgE binds to mast cells and basophils,

causing them to undergo causing them to undergo degranulationdegranulation and release several mediators:and release several mediators:

HistamineHistamine: : ProstaglandinsProstaglandins:: LeukotrienesLeukotrienes: :

Anaphylactic shockAnaphylactic shock: Massive drop in blood : Massive drop in blood pressure. Can be fatal in minutes.pressure. Can be fatal in minutes.

Type I HypersensitivityType I Hypersensitivity(Anaphylactic) (Anaphylactic)

Reactions/AllergyReactions/Allergy Exposure to an allergen activates B

cells to form IgE secreting plasma cells

Secreted IgE molecules bind to Fce receptors on mast cells

A subsequent exposure to the allergen results in crosslinking of the bound IgE which triggers the release of various compounds

Mast Cells and the Allergic ResponseMast Cells and the Allergic Response

Mast Cells and the Allergic ResponseMast Cells and the Allergic Response

Examples of type 1Examples of type 1

Atopy Atopy Anaphylaxis Anaphylaxis AsthmaAsthma

Type II Hypersensitivity Type II Hypersensitivity (Cytotoxic) Reactions/antibody-(Cytotoxic) Reactions/antibody-

dependentdependent Involve activation of Involve activation of complementcomplement by IgG or IgM by IgG or IgM

binding to an antigenic cell.binding to an antigenic cell.

Antigenic cell is lysedAntigenic cell is lysed

Transfusion reactions:Transfusion reactions: ABO Blood group systemABO Blood group system: Type O is universal donor. : Type O is universal donor.

Incompatible donor cells are lysed as they enter Incompatible donor cells are lysed as they enter bloodstream.bloodstream.

Rh Blood Group SystemRh Blood Group System: 85% of population is Rh : 85% of population is Rh positive. Those who are Rh negative can be positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells.sensitized to destroy Rh positive blood cells.

Hemolytic disease of newbornHemolytic disease of newborn: Fetal cells are : Fetal cells are destroyed by maternal anti-Rh antibodies that cross the destroyed by maternal anti-Rh antibodies that cross the placenta.placenta.

Hemolytic disease of the newborn is caused by type II hypersensitivity reactions

When an Rh- mother carries an Rh+ fetus

Examples of type IIExamples of type II

Autoimmune hemolytic anemia Autoimmune hemolytic anemia Thrombocytopenia Thrombocytopenia Erythroblastosis fetalis Erythroblastosis fetalis Goodpasture's syndrome Goodpasture's syndrome

Type III Hypersensitivity Type III Hypersensitivity (Immune Complex) (Immune Complex)

ReactionsReactions Involve reactions against Involve reactions against solublesoluble antigens antigens

circulating in serum.circulating in serum. Usually involve IgA antibodies.Usually involve IgA antibodies. Antibody-Antigen immune complexes are Antibody-Antigen immune complexes are

deposited in organs, activate complement, deposited in organs, activate complement, and cause inflammatory damage.and cause inflammatory damage.

GlomerulonephritisGlomerulonephritis: Inflammatory kidney : Inflammatory kidney damage.damage.

Occurs with slightly high antigen-antibody Occurs with slightly high antigen-antibody ratio is present.ratio is present.

Immune Complex Mediated Immune Complex Mediated HypersensitivityHypersensitivity

Type III HypersensitivityType III HypersensitivityInsect bites—if an individual has been previously sensitized and has circulating antibodies, the initial reaction will be type I at the site of the bite and 4-8 hours later a type III reaction might develop

Arthus reaction: deposits of immune complexes draw neutrophils, leading to an accumulation of fluid (edema) and RBC’s (erythema)

Severity of the reaction varies from mild swelling and redness to tissue necrosis

Type III reactions can also be generalized (as opposed to localized to a specific tissue)

Large amounts of circulating antigen can form immune complexes which are not easily cleared by phagocytic cells

Example: “serum sickness” following the injection of an anti-toxin

Examples of type IIIExamples of type III

Serum sickness Serum sickness Arthus reaction Arthus reaction Systemic lupus erythematosus (SLE) Systemic lupus erythematosus (SLE)

Type IV (Cell-Mediated) Type IV (Cell-Mediated) Reactions/Delayed-type Reactions/Delayed-type

hypersensitivity/antibody-hypersensitivity/antibody-

independentindependent Involve reactions by TInvolve reactions by TDD memory cells. memory cells.

First contact sensitizes person.First contact sensitizes person. Subsequent contacts elicit a reaction.Subsequent contacts elicit a reaction.

Reactions are Reactions are delayeddelayed by one or more days by one or more days (delayed type hypersensitivity).(delayed type hypersensitivity).

Delay is due to migration of macrophages and T cells Delay is due to migration of macrophages and T cells to site of foreign antigens.to site of foreign antigens.

Reactions are frequently displayed on the skin: Reactions are frequently displayed on the skin: itching, redness, swelling, pain.itching, redness, swelling, pain.

Tuberculosis skin testTuberculosis skin test Poison ivyPoison ivy MetalsMetals Latex in gloves and condoms (3% of health care Latex in gloves and condoms (3% of health care

workers)workers) Anaphylactic shock may occur.Anaphylactic shock may occur.

Type IV MechanismType IV Mechanism

APC resident in the APC resident in the skin process antigen skin process antigen and migrate to and migrate to regional lymph nodes regional lymph nodes where they activate T where they activate T cellscellsSensitised T cells Sensitised T cells migrate back to the migrate back to the the skin where they the skin where they produce cytokines produce cytokines which attract which attract macrophages which macrophages which cause tissue damagecause tissue damage

Type IV or delayed type hypersensitivity – cell mediated

Many contact dermatitis reactions are mediated by TH1 cells

The molecules (such as pentadecacatechol) complex with skin proteins and this complex is then internalized by antigen presenting cells, processed and presented with Class II MHC molecules which are recognized by appropriate TH1 cells and which are now “sensitized” to pentadecacatecholSubsequent exposure to pentadecacatechol will activate these TH1 cells and induce cytokine production; approximately 48 to 72 hours after this second exposure macrophages accumulate at the site and release lytic enzymes that cause the redness and pustule formation of poison oak exposure

Examples of Type IVExamples of Type IV

Contact dermatitis Contact dermatitis Mantoux test Mantoux test Chronic transplant rejection Chronic transplant rejection Multiple sclerosis Multiple sclerosis

Type V Hypersensitivity / Auto Type V Hypersensitivity / Auto immuneimmune

This is an additional type that is sometimes This is an additional type that is sometimes (often in Britain) used as a distinction from (often in Britain) used as a distinction from Type 2 Type 2

Instead of binding to cell surface Instead of binding to cell surface components, the antibodies recognize and components, the antibodies recognize and bind to the cell surface receptors , which bind to the cell surface receptors , which either prevents the intended ligand binding either prevents the intended ligand binding with the receptor or mimics the effects of with the receptor or mimics the effects of the ligand, thus impairing cell signalingthe ligand, thus impairing cell signaling

Examples of Type VExamples of Type V

Grave's disease Grave's disease Myasthenia Gravis Myasthenia Gravis Hashimoto's thyroiditis Hashimoto's thyroiditis Systemic lupus erythematosus Systemic lupus erythematosus

Thank you