Hypersensitivity 1 4

7/28/2019 Hypersensitivity 1 4

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HYPERSENSITIVITY


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dr R. Lia K. Iswara, MS, SpMK (K)


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HYPERSENSITIVITY

A damage to host mediated by

preexisting an abnormalimmune response to self or

foreign antigen


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Hypersensitivity (Allergy):Four Types of Hypersensitivity Reactions:

Type I: Anaphylactic/Immediate Reactions

Type II: Cytotoxic Reactions

Type III: Immune Complex Reactions

Type IV: Cell-Mediated/delayed Reactions


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Type I (Anaphylactic) ReactionsOccur within minutes of exposure to antigen

Antigens combine with IgE antibodies

IgE binds to mast cells and basophils, causingthem to undergo degranulationand release

several mediators:


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Type I (Anaphylactic) ReactionsHistamine: Dilates and increases permeability of

blood vessels (swelling and redness), increases

mucus secretion (runny nose), smooth muscle

contraction (bronchi).

Prostaglandins: Contraction of smooth muscle of

respiratory system and increased mucus secretion.

Leukotrienes: Bronchial spasms.

Anaphylactic shock: Massive drop in blood

pressure. Can be fatal in minutes.


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Mast Cells and the Allergic Response


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Role of Mast Cells & Basophils

Mast cells located in the connective tissue of

all organs (in lungs, skin, GI and genital tract)

Basophils circulate in blood into tissues

Each cell can bind 10,000-40,000 IgE

Cytoplasmic granules contain

activecytokines, histamine, etc

Cells degranulate when stimulated by allergen


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Chemical mediators


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Mast Cells and the Allergic Response


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Mechanism of Type I

Sensitizing dose

first contact with allergen(specific B cells form IgE which attaches tomast cells and basophils)

Provocativedose - subsequent exposure withthe same allergen (binds to the IgE-mast cellcomplex)

Degranulation : releases mediators withphysiological effects (vasodilation andbronchoconstriction)

Symptoms : rash, itching, redness, increasedmucous discharge, pain, swelling, and difficultybreathing


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Systemic Anaphylaxis

Sudden respiratory and circulatory

disruption that can be fatal in a few

minutesAllergen and route are variable

Bee stings, antibiotics or serum injection


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Strategies for circumventing

allergic attacks


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Blocking Ab


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Type II (Cytotoxic) ReactionsInvolve activation ofcomplement by IgG or

IgM binding to an antigenic cell.

Antigenic cell is lysed.

Transfusion reactions:

ABO Blood group system: Type O is universal

donor. Incompatible donor cells are lysed as theyenter bloodstream.


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Type II (Cytotoxic) ReactionsRh Blood Group System: 85% of population is Rh

positive. Those who are Rh negative can be

sensitized to destroy Rh positive blood cells.

Hemolytic disease of newborn: Fetal cells are destroyed

by maternal anti-Rh antibodies that cross the placenta.


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Immunopathology

Definition - Type II reaction

Cytotoxic antibodies of IgM or IgG

subtype formed against an antigen on a

cell surface, or more rarely, against a

component of the extracellular matrix.

Usually, the binding of the antibody to the

cellular antigen causes complement

fixation (activation).

The membrane attack complex (MAC) of

complement then kills the cell.


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Type III (Immune Complex) ReactionsInvolve reactions against solubleantigens

circulating in serum.

Antibody-Antigen immune complexes are

deposited in organs, activate complement, and

cause inflammatory damage.

Glomerulonephritis: Inflammatory kidneydamage.

Occurs with slightly high antigen-antibody

ratio is present.


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Immunopathology

Definition - Type III reaction

Type III reactions involve immunecomplexes of antibody and antigen.

Antibodies are of IgM or IgG type, but theantigen is usually a soluble antigen.

Antibodies form immune complexes withthese antigens, and the complexes aredeposited in tissue activatecomplement.

Kidney and skin are most often affected.


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Immunopathology

Type III hypersensitivity reaction

Immune complexes of ideal size areusually formed with slight antigen excess.

Larger complexes removed by themononuclear phagocyte system.

Complexes likely induce disease byattaching to the Fc or C3b receptors onpolymorphs, and trigger release ofcytokines, attracting more PMNs, andinitiating more complement fixation.


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Immune Complex Mediated Hypersensitivity


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SYSTEMIC LUPUS ERYTHEMATOSUS

Detection of immune complexes in serum


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Detection of immune complexes in serum


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Type IV (Cell-Mediated) ReactionsInvolve reactions by TD memory cells.

First contact sensitizes person.

Subsequent contacts elicit a reaction.

Reactions are delayedby one or more days

(delayed type hypersensitivity).

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


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Type IV (Cell-Mediated) Reactions

Reactions are frequently displayed on the skin:

itching, redness, swelling, pain. Tuberculosis skin test

Poison ivy

Metals

Latex in gloves and condoms (3% of health care workers)

Anaphylactic shock may occur.


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Type IV Hypersensitivity

Cell-mediated

A delayed response to Ag involvingactivation of and damage by T cells

Delayed allergic response

skin responseto allergens tuberculin skin test, contactdermititis from plants, metals, cosmetics

Graft rejection

reaction of cytotoxic Tcells directed against foreign cells of agrafted tissue; involves recognition offoreign HLA


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ImmunopathologyTransplant rejection

Mechanisms involved in transplant

rejection

T cell mediateddelayed type hypersensitivity

Direct pathway via recipient CD4+ and CD8+

recognition of MHC Class I antigens on donor APCs

Indirect pathway whereby processing of antigen by

the recipients APCs is required

Antibody mediatedimmediate hypersensitivity


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Allergic Contact Dermatitis Response to


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Allergic Contact Dermatitis Response to

Poison Ivy Hapten


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Contact dermatitis reaction to leather


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Granuloma in a leprosy

i i i


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Delayed hypersensitivity


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Comparison of hypersensitivity


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Comparison of hypersensitivity


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Hypersensitivity 1 4