sequence4_hypersensitivity type 4&5.pptx

8/14/2019 sequence4_hypersensitivity type 4&5.pptx

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Cell mediated hypersensitivityor Delayed hypersensitivity

Type IV Hypersensitivity


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;It is mediated by cells circulatingantibody and complement are not.involved Many reactions to

immunologic insult involve both.cellular and humoral components It is mediated by soluble factors

( )lymphokines released by the

.sensitized T lymphocytes The

lymphokines have biologicalactivities affecting various cell

.types



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Those that may be used as examples ofdelayed type hypersensitivity

:response includes

Tuberculin skin reaction Contact sensitivity Granulomatous hypersensitivity



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This form of hypersensitivity was.originally described by Koch

The skin reaction is frequently used

to test for sensitivity to theorganisms following previous.exposure

This form of hypersensitivity may

-also be induced by non microbial,antigens such as beryllium and.zirconium

Tuberculin-type Hypersensitivity


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The tuberculin skin test reaction.principally involves monocytes

The tuberculin skin test is an

example of the recall response tosoluble antigen previously.encountered during infection



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-Tuberculin like delayed type( )hypersensitivity DTH reactions are

.used practically in two ways

,First reaction to soluble

antigens from a pathogendemonstrates past infection with

.that pathogen Thus tuberculin

reactivity confirms pastinfection with . ,M tuberculosisbut not necessarily active

.disease



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,Second DTH responses to frequentlyencountered microbes are a general

- .measure of cell mediated immunity This can be tested with intradermal

injection of single antigens from common,pathogens or a multipuncture devicewhich delivers seven common microbial

.antigens in a standardized fashion

Loss of recall responses to specific

antigens occurs in a wide range of-diseases and infections which impair T

,cell function and during therapy withcorticosteroids or immunosuppressive

.agents



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Contact hypersensitivity ischaracterized by an eczematous

reaction at the point of contact.with the allergen

It is often seen following contact, ,with agents such as nickel chromate

rubber accelerators and.pentadecacatechol

Contact with irritants that damageskin by toxic mechanisms notmediated by hypersensitivity can

.also produce eczema

Contact hypersensitivity


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The Langerhans cell is the principal-antigen presenting cell

Contact hypersensitivity is primarily

,an epidermal reaction and the ,dendritic Langerhans cell located,in the suprabasal epidermis is the

-principal antigen presenting cell

( ) . APC involved Langerhans cells are,inactivated by ultraviolet B whichcan thus prevent or alleviate the

.effects of contact hypersensitivity



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,In vitro Langerhans cells act asAPCs and are more potent in this

. regard than monocytes Langerhans-cells take up hapten modified

proteins by micropinocytosis and-under the influence of interleukin 1

( - ) ( )IL 1 and tumor necrosis factor TNF

from keratinocytes and other cells

,undergo maturation increase the-expression of MHC and co stimulatory

molecules and migrate to draining

.lymph nodes



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Keratinocytes produce a range ofcytokines important to the contact

.hypersensitivity - ,IL 3 can activate Langerhans cells

- ,co stimulate proliferative responsesrecruit mast cells and induce thesecretion of immunosuppressive.cytokines These latter dampen the

immune response and induce the.clonal anergy in TH1 cells



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Keratinocytes can be activated by a,number of stimuli including

.allergens and irritants Activatedkeratinocytes produce

immunostimulatory cytokines such asTNF - -and granulocyte macrophage

- ( - )colony stimulating factor GM CSF

.which activate Langerhans cells



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A contact hypersensitivity reaction:has two stages sensitization and

allicitation

Sensitization produces a

population of memory T cells Elicitation involves recruitment

+of CD4 lymphocytes and

monocytes



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Sensitization takes 10 14 days in. ,humans Once absorbed the hapten

with a protein and is internalized ,by epidermal Langerhans cells which

leave the epidermis and migrates asveiled cells through the afferent

lymphatics to the paraoctical areas.of regional lymph nodes Here they

-present hapten protien conjugates to+ ,CD4 lymphocytes producing a

+ .population of memory CD4 T cells

Sensitization


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Langerhans cells carrying the hapten(carrier complex 1)move from the

,epidermis to the dermis where they-present the hapten carrier complex to

+ (memory CD4 T cells 2) Activated+CD4 T cells released IFN, which

- (induces expression of ICAM 1 3) and(later MHC class II molecules 4) on

the surface of keratinocytes and onthe endothelial cells of dermal

capillaries and activates

-, -keratinocytes such as IL 1 IL 6 and

-GM CSF

Elicitation


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(5) +Non antigen specific CD4 T cellsare attracted to the site by

(cytokinesis 6) and may bind to-keratinocytes via ICAM 1 and class II

.molecules Activates macrophages are,also attracted to the skin but this.occurs later Thereafter the reaction

.stars to downregulate This

doenregulation may be influenced by,eicosanoids such as PGE produced byactivated keratinocytes and

(macrophages 7) has been shown to-induce a specific inhibitor of IL 1

activity

Elicitation


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Granulomatous hypersensitivity isclinically the most important form of

,TYPE IV hypersensitivity and causesmany of the pathological effects in

disease that involves T cells mediated.immunity It usually results from the persistence

within macrophages of intracellular

microorganisms or other particles that.the cells is unable to destroy Thisprocess results in epithelioid cell

.granuloma formation This histologicalappearance of the granuloma reaction is

quite different from that of the-

GRANULOMATOUS HYPERSENSITIVTY


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,However they often result fromsensitization to similar microbial

.antigens Immunological granulomaformation also occurs in the sensitivity

,reactions to zirconium and beryllium and,in sarcoidosis although in the latter the.antigen is unknown

Foreign body granuloma formation occur with,talc silica and a variety of other

.particulate agents In this casemacrophages are unable to digest the.inorganic matter These non immunological

granulomas may be distinguished by the.absence of lymphocytes in the lesion



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An immunological granuloma typicallyhas a core of epithelioid cells and

,macrophages sometimes with giant. ,cells In some diseases such as

,tuberculosis this central area may,have a zone of necrosis with

complete destruction of all cellular.architecture The

/macrophage epithelioid core is,surrounded by a cuff of lymphocytes

and there may also be considerable

fibrosis caused by proliferation of

fibroblasts and increased collagen



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DELAYED HYPERSENSITIVITYREACTIONS

Type Reaction

time

Clinical

appearance

Histology Antigen

contact 48-72 hr Eczema Lymphocytes,latermacrophages,

oedema ofepidermidis

Epidermal e.g.nickel, rubber,poison ivy

tuberculin 48-72 hr Local induration Lymphocytes,monocytes,macrophages

Intradermal e.g.tuberculin

granuloma 21-28 days Hardening e.g.

skin or lungs

Macrophages,

epithelioid cells,giant cells,fibrosis

Persistent Ag or

Ag/Abcomplexes ornon-immunoglobine.g. talc


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Receptor mediated hypersensitivity

Type V Hypersensitivity


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This reaction occur when IgGclass antibodies directed

towards cell surfaces antigens

have either a stimulating orinhibitory effect on their.target

Cells are signaled by agents such, -as hormones mainly amino acid

:based hormones These hormones cannot pass through

plasma membranes because they are



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Type V hypersensitivity has beenadded as a distinction from Type

.II

This additional class of reactionrefers to stimulatory,hypersensitivity where instead

of binding to cell surface

components and destroying the,cells IgG receptors thus either,prevents ligand binding or

mimics the effect of the

,endogenous ligand thus impairing



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This is a useful distinction to TypeII reactions where the cytotoxic

binding of antibody causes cell

.death

Stimulatory hypersensitivity occurswhen the autoantibodies cause

inappropriate stimulation of the

.cell



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Colby C. Evans, M.D.

John D. Fleming, M.B., B.S

New England Journal of MedicineAugust 2008

Allergic Contact Dermatitis

from a Henna Tattoo


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Temporary henna tattooing is a custom.at weddings in much of the world The

( )dyeing agent hennotannic acid

.rarely leads to skin sensitization,However tattoo henna is often mixed

( )with paraphenylenediamine PPD to.hasten drying and darken the color

PPD is a common allergen that is.also found in permanent hair dyes

Allergic Contact Dermatitis from a HennaTattoo


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Allergens that cause reactions inpatients who are sensitive to PPD

include sunscreens containing

,aminobenzoic acid certain local, .anesthetics and sulfonamides -The patient was treated high potency

,topical corticosteroids and the

,lesions resolved although withextensive postinflammatory.hyperpigmentation

Allergic Contact Dermatitis from aHenna Tattoo


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Allergic Contact Dermatitis from aHenna Tattoo

sequence4_hypersensitivity type 4&5.pptx

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