REAKSI HIPERSENSITIVITAS

dr Atik Sutisna, SpAn

Vice Dean for Academic affair Lecturer of Anaesthesiology and Reanimation, Faculty of Medicine, Unswagati , Cirebon

Vice Director for Medical services and ursing !ead of Anaesthesia and "ntensive Care Unit #utera $ahagia !os%ital, Cirebon

Immunologic Mechanisms of Tissue Damage

(Immuopathology)

Immunopathology
Exaggerated immune response may lead to different forms of tissue damage 1) An overactive immune response: produce more damage than it prevents e.g. hypersensitivity reactions and graft rejection

2) ailure of appropriate recognition: as in autoimmune diseases

Hypersensitivity Reaction
!ypersensitivity or allergy
" An immune response results in exaggerated reactions harmful to the host " #here are four types of hypersensitivity reactions: #ype I$ #ype II$ #ype III$ #ype I% " #ypes I$ II and III are anti&ody mediated " #ype I% is cell mediated

Type I: Immediate hypersensitivity

" An antigen reacts 'ith cell fixed anti&ody (Ig E) leading to release of solu&le molecules An antigen (allergen) solu&le molecules (mediators) " (olu&le molecules cause the manifestation of disease " (ystemic life threatening) anaphylactic shoc* " +ocal atopic allergies) &ronchial asthma$ hay fever and food allergies

Pathogenic mechanisms
" irst exposure to allergen Allergen stimulates formation of anti&ody (Ig E type) Ig E fixes$ &y its c portion to mast cells and &asophiles " (econd exposure to the same allergen It &ridges &et'een Ig E molecules fixed to mast cellsleading to activation and degranulation of mast cells and release of mediators

Pathogenic mechanisms
" #hree classes of mediators derived from mast cells: ,) -reformed mediators stored in granules (histamine) 2) .e'ly sensiti/ed mediators: leu*otrienes$ prostaglandins$ platelets activating factor 0) 1yto*ines produced &y activated mast cells$ &asophils e.g. #. $ I+0$ I+23$ I+24 I+210$ chemo*ines " #hese mediators cause: smooth muscle contraction$ mucous secretion and &ronchial spasm$ vasodilatation$ vascular permea&ility and edema

Anaphylaxis
" (ystemic form of #ype I hypersensitivity " Exposure to allergen to 'hich a person is previously sensiti/ed " Allergens: 5rugs: penicillin (erum injection : anti2diphtheritic or ant2tetanic serum anesthesia or insect venom " 1linical picture: (hoc* due to sudden decrease of &lood pressure$ respiratory distress due to &ronhospasm$ cyanosis$ edema$ urticaria " #reatment: corticosteroids injection$ epinephrine$ antihistamines

Atopy
" +ocal form of type I hypersensitivity " Exposure to certain allergens that induce production of specific Ig E " Allergens : Inhalants:dust mite faeces$ tree or pollens$ mould spor. Ingestants: mil*$ egg$ fish$ choclate 1ontactants: 'ool$ nylon$ animal fur 5rugs: penicillin$ salicylates$ anesthesia insect venom " #here is a strong familial predisposition to atopic allergy " #he predisposition is genetically determined

Methods of diagnosis
1) !istory ta*ing for determining the allergen involved 2) (*in tests: Intradermal injection of &attery of different allergens A 'heal and flare (erythema) develop at the site of allergen to 'hich the person is allergic 0) 5etermination of total serum Ig E level 3) 5etermination of specific Ig E levels to the different allergens

Management
1) Avoidance of specific allergen responsi&le for condition 2) !yposensiti/ation: Injection gradually increasing doses of extract of allergen 2 production of Ig 6 &loc*ing anti&ody 'hich &inds allergen and prevent com&ination 'ith Ig E 2 It may induce # cell tolerance 0) 5rug #herapy: corticosteroids injection$ epinephrine$ antihistamines

Type II: Cytotoxic or Cytolytic Reactions

" An anti&ody (Ig 6 or Ig 7) reacts 'ith antigen on the cell surface " #his antigen may &e part of cell mem&rane or circulating antigen (or hapten) that attaches to cell mem&rane

Mechanism of Cytolysis
" 1ell lysis results due to :
1) 1omplement fixation to antigen anti&ody complex on cell surface #he activated complement 'ill lead to cell lysis 2) -hagocytosis is enhanced &y the anti&ody (opsinin) &ound to cell antigen leading to opsoni/ation of the target cell

Mechanism of cytolysis
0) Anti&ody depended cellular cytotoxicity (A511): 2 Anti&ody coated cells e.g. tumour cells$ graft cells or infected cells can &e *illed &y cells possess c receptors 2 #he process different from phagocytosis and independent of complement 2 1ells most active in A511 are: .8$ macrophages$ neutrophils and eosinophils

Clinical Conditions
1) #ransfusion reaction due to A9: incompati&ility 2) ;h2incompata&ility (!aemolytic disease of the ne'&orn) 0) Autoimmune diseases
#he mechanism of tissue damage is cytotoxic reactions e.g. (+E$ autoimmune haemolytic anaemia$ idiopathic throm&ocytopenic purpura$ myasthenia gravis$ nephrotoxic nephritis$ !ashimoto<s thyroiditis

3)

A non2cytotoxic #ype II hypersensitivity is 6raves<s disea

It is a form of thyroditits in 'hich anti&odies are produced against #(! surface receptor #his lead to mimic the effect of #(! and stimulate cells to over2 produce thyroid hormones

Clinical Conditions
42 6raft rejection cytotoxic reactions:
In hyperacute rejection the recipient already has performed anti&ody against the graft

=2 5rug reaction:
-enicillin may attach as haptens to ;91s and induce anti&odies 'hich are cytotoxic for the cell2drug complex leading to haemolysis >uinine may attach to platelets and the anti&odies cause platelets destruction and throm&ocytopenic purpura

Type III Hypersensitivity

Immune Complex e!i"te! #e"$tion

Type III% Immune Complex

e!i"te! #e"$tion

"?hen anti&odies (Ig 6 or Ig 7) and antigen coexist immune complexes are formed "Immune complexes are removed &y reticuloendoth. syst. "(ome immune complexes escape phagocytosis "Immune complexes deposited in tissues on the &asement mem&rane of &lood vessels and cause tissue injury

! Arthus Reaction
" #his is a local immune complex deposition phenomenon e.g. dia&etic patients receiving insulin su&cutaneously edema erythema necrosis

" +ocal reactions in the form of

deposited " Immune complexes in small &lood vessels vasculitis microthrom&i formation vascular occlusion necrosis

leading to

"! #erum #ic$ness

" A systemic immune complex phenomenon " Injection of large doses of foreign serum " Antigen is slo'ly cleared from circulation " Immune complexes are deposited in various sites fever urticaria arthralgia lymphadenopathy splenomegaly glomerulonephritis antidiphtheritic serum e.g. treatment 'ith penicillin

" 1@ days after injection

Clini$"l $on!itions o& Type III Hypersensitivity

5iseases produced &y immune complexes are those in 'hich antigens persists 'ithout &eing eliminated as: a2 ;epeated exposure to extrinsic antigen &2 injection of large amounts of antigens c2 -ersistent infections d2 Autoimmunity to self components

Mechanism %f Tissue In&ury

Immune complexes trigger inflammatory processes:
activate 1) Immune complexes the complement release anaphylatoxins
10a$ 14a

stimulate release degranulation of &asophiles and mast cells histamine !istamine vascular permea&ility and help deposition of immune complexes

2) .eutrophils are attracted to the site &y immune complexes and release lysosomal en/ymes 'hich damage tissues and intensify the inflammat. -ro. 0) -latelets are aggregated 'ith t'o conseAuences a2 release of histamine &2 form of microthrom&i 'hich lead to ischemia

&y%e "V Cell Mediated Delayed &y%e !y%ersensitivity

Type I'% Cell e!i"te! (el"ye! Type Hypersensitivity

" #2cells cause tissue injury &y triggering 5#! reactions &y #!1 or directly *illing target cells &y 15B

" #!1 and 15B # cells secrete cyto*ines (I .2C and #. ) attract lymphocytes activate macrophages induce inflammation

" 1yto*ines

" #issue damage results from products of activated macrophages

Tu'erculin (Type Hypersensitivity

" ?hen --5 is injected intradermally in sensiti/ed person " +ocal indurated area appears injection site (3B2D2 hs) " Indurations due to accumulation :f: macrophages and lymphocytes " (imilar reactions o&served in diseases e.g. &rucellosis$ lepromin test in leprosy$ rei<s test in lymphogranuloma venereum

)ranulomatous lesions
" In chronic diseases : #.9.$ +eprosy$ schistosomiases " Intracellular organisms resist destruction &y macrophag. " -ersistent antigen in tissues stimulate local 5#! reaction " 1ontinuous release of cyto*ines leads to accumulation of macrophages 'hich give rise to epitheloidal and giant cell granuloma

Contact Dermatitis
" 1ontact of s*in 'ith chemical su&stances or drugs e.g. poison$ hair dyes$ cosmetics$ soaps$ neomycin " #hese su&stances enter s*in in small molecules " #hey are haptens that attached to &ody proteins$ form immunogenic su&stances " 5#! reaction to these immunogenic su&st. lead to: ec/yma rash vesicular eruption

inflammtory reaction of s*in in

Type I' Hypersensitivity Clini$"l Con!itions

1) Auto immune diseases and graft rejection are due to in part to delayed hypersensitivity reactions 2) Insulin dependant dia&etes mellitus #2cells invade the pancreatic islets and specifically destroy insulin secreting &eta cells

Thanks