Hypersensitivity 2016

8/16/2019 Hypersensitivity 2016

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Hipersensitivitas


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Immunologic Mechanisms

of Tissue Damage(Immuopathology)


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Mast-cell degranulation

Mediator release

N K

Cytotoxic action

Complement mediated lysis

I II

Dharmana

E


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Immune-complex deposition

IL-4,5

IFN-γ

IFN-γ,IL-2

Th2

Th1

CTL

CTL

Th0

Cell-mediated hypersensitivity

III IV

Dharmana

E


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Immunopathology

Exaggerated immune response may lead to differentforms of tissue damage

1) An oera!tie immune response" produ!e more damage than it preents

e#g# hypersensitiity rea!tions and graft re$e!tion

2) %ailure of appropriate re!ognition"

as in autoimmune diseases


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Hypersensitivity Reaction

&ypersensitiity or allergy ' An immune response results in exaggerated

rea!tions harmful to the host

' There are four types of hypersensitiity rea!tions"

Type I Type II Type III Type I

' Types I II and III are anti*ody mediated

' Type I is !ell mediated


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!athogenic mechanisms' %irst exposure to allergen

Allergen stimulates formation of anti*ody (Ig E type) Ig E fixes *y its %! portion to mast !ells and *asophiles

' ,e!ond exposure to the same allergen

It *ridges *et+een Ig E mole!ules fixed to mast!ellsleading to a!tiation and degranulation of mast!ells and release of mediators


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!athogenic mechanisms

' Three !lasses of mediators deried from mast !ells"

/) 0reformed mediators stored in granules (histamine)

2) e+ly sensitied mediators"

leu.otrienes prostaglandins platelets a!tiating fa!tor

3) Cyto.ines produ!ed *y a!tiated mast !ells *asophils

e#g# T% IL3 IL-4 IL-5 IL-13 !hemo.ines

' These mediators !ause" smooth mus!le !ontra!tion

mu!ous se!retion and *ron!hial spasm asodilatation

as!ular permea*ility and edema


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"naphylaxis

' ,ystemi! form of Type I hypersensitiity

' Exposure to allergen to +hi!h a person is preiously sensitied

' Allergens"

Drugs" peni!illin ,erum in$e!tion " anti-diphtheriti! or ant-tetani! serum

anesthesia or inse!t enom

' Clini!al pi!ture"

,ho!. due to sudden de!rease of *lood pressure respiratorydistress due to *ronhospasm !yanosis edema urti!aria

' Treatment" !orti!osteroids in$e!tion epinephrine antihistamines


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"topy' Lo!al form of type I hypersensitiity

' Exposure to !ertain allergens that indu!e produ!tion ofspe!ifi! Ig E

' Allergens " Inhalants"dust mite fae!es tree or pollens mould spor#

Ingestants" mil. egg fish !ho!late

Conta!tants" +ool nylon animal fur

Drugs" peni!illin sali!ylates anesthesia inse!t enom

' There is a strong familial predisposition to atopi! allergy

' The predisposition is geneti!ally determined


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Methods of diagnosis

1) &istory ta.ing for determining the allergen inoled

2) ,.in tests"

Intradermal in$e!tion of *attery of different allergensA +heal and flare (erythema) deelop at the site of

allergen to +hi!h the person is allergi!

3) Determination of total serum Ig E leel

4) Determination of spe!ifi! Ig E leels to the differentallergens


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Management

1) Aoidan!e of spe!ifi! allergen responsi*le for !ondition

2) &yposensitiation"

In$e!tion gradually in!reasing doses of extra!t of allergen

- produ!tion of Ig 6 *lo!.ing anti*ody +hi!h *inds

allergen and preent !om*ination +ith Ig E

- It may indu!e T !ell toleran!e

3) Drug Therapy"

!orti!osteroids in$e!tion epinephrine antihistamines


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Type II Cytotoxic or Cytolytic Reactions

' An anti*ody (Ig 6 or Ig 7) rea!ts +ith

antigen on the !ell surfa!e

' This antigen may *e part of !ell mem*rane

or !ir!ulating antigen (or hapten) thatatta!hes to !ell mem*rane


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Mechanism of Cytolysis

' Cell lysis results due to "

1) Complement fixation to antigen anti*ody

!omplex on !ell surfa!e The a!tiated !omplement +ill lead to !ell lysis

2) 0hago!ytosis is enhan!ed *y the anti*ody (opsinin) *ound to !ell antigen leading toopsoniation of the target !ell


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Clinical Conditions

1) Transfusion rea!tion due to A9: in!ompati*ility

2) ;h-in!ompata*ility (&aemolyti! disease of the ne+*orn)

3) Autoimmune diseases The me!hanism of tissue damage is !ytotoxi! rea!tions e#g# ,LE autoimmune haemolyti! anaemia idiopathi!

throm*o!ytopeni! purpura myasthenia grais nephrotoxi!nephritis &ashimoto


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Clinical Conditions

5- 6raft re$e!tion !ytotoxi! rea!tions"

In hypera!ute re$e!tion the re!ipient already hasperformed anti*ody against the graft

=- Drug rea!tion" 0eni!illin may atta!h as haptens to ;9Cs andindu!e anti*odies +hi!h are !ytotoxi! for the

!ell-drug !omplex leading to haemolysis

>uinine may atta!h to platelets and the anti*odies

!ause platelets destru!tion and throm*o!ytopeni!

purpura


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Type III Hypersensitivity

Immune Complex Mediated Reaction


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Type III: Immune Complex Mediated Reaction

'?hen anti*odies (Ig 6 or Ig 7) and antigen !oexistimmune !omplexes are formed

'Immune !omplexes are remoed *y reti!uloendoth# syst#

',ome immune !omplexes es!ape phago!ytosis

'Immune !omplexes deposited in tissues on the *asement mem*rane of *lood essels and !ause tissue in$ury


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Mechanism #f Tissue In$ury

Immune !omplexes trigger inflammatory pro!esses"

a!tiate release1) Immune !omplexes the !omplement anaphylatoxins C3a C5a

stimulate release

degranulation of *asophiles and mast !ells histamine

&istamine as!ular permea*ility and help deposition of immune !omplexes

2) eutrophils are attra!ted to the site *y immune !omplexes and release

lysosomal enymes +hi!h damage tissues and intensify the inflammat# 0ro#

3) 0latelets are aggregated +ith t+o !onse@uen!es

a- release of histamine

*- form of mi!rothrom*i +hi!h lead to is!hemia


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Clinical conditions of Type III Hypersensitivity

Diseases produ!ed *y immune !omplexes are those in

+hi!h antigens persists +ithout *eing eliminated as"

a- ;epeated exposure to extrinsi! antigen

*- in$e!tion of large amounts of antigens

!- 0ersistent infe!tions

d- Autoimmunity to self !omponents

% " th R ti


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%- "rthus Reaction

' This is a lo!al immune !omplex deposition phenomenon

e#g# dia*eti! patients re!eiing insulin su*!utaneously

edema

' Lo!al rea!tions in the form of erythema

ne!rosis

deposited

' Immune !omplexes in small *lood essels

as!ulitis

leading to mi!rothrom*i formation

as!ular o!!lusion

ne!rosis


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&- 'erum 'ic(ness ' A systemi! immune !omplex phenomenon

' In$e!tion of large doses of foreign serum ' Antigen is slo+ly !leared from !ir!ulation

' Immune !omplexes are deposited in arious sites

feer urti!aria

' 1 days after in$e!tion arthralgia

lymphadenopathy

splenomegaly

glomerulonephritis

antidiphtheriti! serum

e#g# treatment +ith peni!illin


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Type III Hypersensitivity Clinical Conditions

3- 0ost-strepto!o!!al glomerulonephritis

glomerulitis asso!iated +ith infe!tie endo!arditis

4- &ypersensitie pneumonitis (farmer lung) immune !omplexes depositition in lung after repeated

inhalation of dust mould spores

5- Endogenous antigen anti*ody !omplexes inoled inautoimmune diseases

e#g# ,LE rheumatoid arthritis


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Type IV

Cell MediatedDelayed Type Hypersensitivity


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Type IV: Cell Mediated

Delayed Type Hypersensitivity

triggering DT& rea!tions *y T&1' T-!ells !ause tissue in$ury *y or

dire!tly .illing target !ells *y CDB

' T&1 and CDB T !ells se!rete !yto.ines (I%- and T%)

attra!t lympho!ytes

' Cyto.ines a!tiate ma!rophages

indu!e inflammation

' Tissue damage results from produ!ts of a!tiated ma!rophages


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Tu)erculin *Type Hypersensitivity

' ?hen 00D is in$e!ted intradermally in sensitied person

' Lo!al indurated area appears in$e!tion site (4B-2 hs)

' Indurations due to a!!umulation :f"

ma!rophages and lympho!ytes

' ,imilar rea!tions o*sered in diseasese#g# *ru!ellosis lepromin test in leprosy %rei


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+ranulomatous lesions

' In !hroni! diseases " T#9# Leprosy s!histosomiases

' Intra!ellular organisms resist destru!tion *y ma!rophag#

' 0ersistent antigen in tissues stimulate lo!al DT& rea!tion

' Continuous release of !yto.ines leads to a!!umulation of

ma!rophages +hi!h gie rise to epitheloidal and giant!ell granuloma


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C


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Contact Dermatitis

' Conta!t of s.in +ith !hemi!al su*stan!es or drugs

e#g# poison hair dyes !osmeti!s soaps neomy!in

' These su*stan!es enter s.in in small mole!ules

' They are haptens that atta!hed to *ody proteins form immunogeni! su*stan!es

' DT& rea!tion to these immunogeni! su*st# lead to"

e!yma

inflammtory rea!tion of s.in in rash

esi!ular eruption


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Type IV Hypersensitivity Clinical Conditions

4) Auto immune diseases and graft re$e!tion are due toin part to delayed hypersensitiity rea!tions

5) Insulin dependant dia*etes mellitus

T-!ells inade the pan!reati! islets and spe!ifi!allydestroy insulin se!reting *eta !ells


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Hypersensitivity 2016

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