REAKSI HIPERSENSITIVITAS

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Hipersensitivitas adalah suatu reaksi yang tidak diharapkan dari respon imun tubuh. Coombs dan Gell membagi menjadi 4 tipe (mekanisme dan waktu): Rx. Hipersensitivitas tipe I Rx. Hipersensitivitas tipe II Rx. Hipersensitivitas tipe III Rx. Hipersensitivitas tipe IV

4 types of hypersensitivity reactions

(hives)

Allergies

Immune complex disease

Delayed-type hypersensitivity

Reaksi Hipersensitivitas tipe I

Reaksi Hipersensitivitas tipe cepat atau anafilaktik Diperantarai IgE Alergenproduksi IgE berikatan spesifik dengan reseptor di permukaan sel mast dan basofil tersensitisasi Kontak berikutnya sederetan reaksi biokimia degranulasi dan pelepasan mediator2 (histamin, leukotrien dan sitokin) reaksi alergi 15-30 menit setelah terpapar antigen, kadang keterlambatan (10-12 jam) Dapat melibatkan kulit (urtikaria dan eksema), mata (konjungtivitis), nasofaring (rinitis), jaringan bronkopulmoner (asma), dan GI tract (gastroenteritis)

Reaksi Hipersensitivitas tipe I.

Contoh: reaksi anafilaksis terhadap bisa hewan, hay fever, urtikaria akibat makanan, dermatitis atopik, rhinitis alergika, konjungtivitis, asma, dll Gejala : ketidaknyamanan ringan sampai kematian Berat ringan gejala dipengaruhi :

antibodi IgE jumlah alergen faktor-faktor lain yang dapat meningkatkan respon (infeksi virus dan polutan)

Biologic effects of mediators

Table 1. Pharmacologic Mediators of Immediate Hypersensitivity MEDIATOR Preformed mediators in granules histamine tryptase kininogenase ECF-A (tetrapeptides) Newly formed mediators bronchoconstriction, mucus secretion, vasodilatation, vascular permeability proteolysis kinins and vasodilatation, vascular permeability, edema attract eosinophil and neutrophils

leukotriene B4
leukotriene C4, D4 prostaglandins D2 PAF

basophil attractant
same as histamine but 1000x more potent edema and pain platelet aggregation and heparin release: microthrombi

Tes diagnostik
Skin test (prick dan intradermal) Kadar total IgE dan IgE spesifik terhadap alergen yang dicurigai (ELISA) IgE tinggi pada kondisi atopik

Terapi:

Antihistamin, adrenalin, bronkodilator, kortikosteroid, menghindari paparan alergen dan immunoterapi

Skin test for allergy

Ragweed Control negative (saline)

Control positve (histamine)

CAUSES
Antigen Ingestants Food Drugs Pollens Dusts Molds Injectants Drugs Stings Vaccines Serum

MECHANISM

PATHOPHYSIOLOGY
Increased Blood Volume Exudation of Cell, fluid protein Pressure of exudate Nerve irritation Constriction of smooth muscle

Allergen interacts with IgE on mast cell

Release of chemical mediators : Histamine SRS-A Kinins Prostaglandins

Capillary dilation

Increased Capillary permebiality

Type I hypersensitivity reaction

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MANIFESTATIONS Respiratory tract Respiratory tract 1. Upper sinus headache 1. Upper sinus headache itching ofof eyes itching eyes tearing, sneezing, tearing, sneezing, watery nasal discharge, watery nasal discharge, itching of nose, itching of nose, throat irritation throat irritation 2. Lungs wheezing, dyspnea, 2. dry cough, tightness dyspnea, Lungs wheezing, in chest
Gastrointestinal Glossitis, cardiospasm Nausea, vomitting Irritable bowel Diarrhea, pruritus ani
Skin Urticaria, pruritus, Angioedema, weeping erthematosus vesico-papular lessions

CLINICAL EXAMPLES

Allergic rhinitis

Conjunctivitis

dry cough, tightness in chest

Asthma

Food allergies

Atopic dermatitis Urticaria

Type I hypersensitivity reaction (continued)

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Reaksi Hipersensitivitas tipe II

Reaksi hipersensitivitas sitotoksik Waktu reaksi : menit - jam Contoh: reaksi transfusi, drug-induced hemolytic anemia, granulositopenia, dan trombositopenia Diperantarai IgM atau IgG dan komplemen Fagosit dan sel K punya peran Interaksi antigen-antibodi pd permukaan sel, IgM atau IgG dgn antigen yang juga merupakan bagian integral membran sel atau telah terserap atau menyatu menjadi membran. Mengaktifkan sistem komplemen dan sel yang terlibat dihancurkan.

CAUSES Antigen Transfusion reaction Erythroblastosis fetalis Drugs Autoantibodies Unknown

MECHANISM

PATHOPHYSIOLOGY

CLINICAL EXAMPLES Hemolytic anemia

Antigen interacts with body cell i.e : Erythrocyte Leucocyte Platelet Vascular endothelium

Reaction of IgG or IgM antobody with antigen on cell Activates complement

Erytrhrocyte hemolysis

Agranulocytosis

Susceptability to infections Purpura Vesicular purpura

Thrombocytopenia Vasculitis

Type II hypersensitivity reaction

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Reaksi Hipersensitivitas tipe III

Reaksi hipersensitivitas kompleks imun / reaksi Arthus 3-10 jam setelah terpapar antigen Diperantarai kompleks imun (antigen-antibodi) Antigen eksogen (bakteri, virus, atau parasit)/endogen (SLE) Contoh: serum sickness,SLE,rx Arthus,lupus nephritis,RA,dll Terbentuk kompleks antigen-antibodi (toksik terhadap jaringan di tempat mereka diendapkan seperti ginjal / paruparu) infiltrasi dinding pembuluh darah kecil aktivasi kaskade komplemen pelepasan bahan aktif secara biologis, termasuk faktor-faktor yang menarik sel-sel fagosit yang akan menfagositosis kompleks tersebut

Type III hypersensitivity reactions (Arthus Reaction) - Ab-Ag Complexes

Critical mediators appear to be C5a-receptor and FcgRIII--probably present on mast cells

CAUSES
Antigen Autoantibodies Drugs Serum Chemicals Foreign antigen Bacteria Virus

MECHANISM

PATHOPHYSIOLOGY

CLINICAL EXAMPLES
Glomerulonephritis Vasculitis Arthus reaction Rheumatoid diseases Serum sickness

Antigen and antibody form an immune complex

Deposits on vessel walls or basement membrane

Tissue destruction Inflammation

Type III hypersensitivity reaction

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Diagnosis:
Biopsi

jaringan (endapan Ig dan komplemen) Kompleks imun pada darah dan penurunan jumlah komplemen

Terapi:
Anti-inflamasi

Reaksi Hipersensitivitas Tipe IV

tipe seluler atau tipe lambat (delayed type hypersensitivity) > 12 jam Contoh klasik: reaksi tuberkulin (Mantoux) yang memuncak 48 jam setelah injeksi antigen Contoh lain: dermatitis kontak, penyakit autoimun dan infeksi seperti tuberkulosis, lepra, granulomatosa, toksoplasmosis, dll

Late stage of an allergic response includes the recruitment of eosinophils and Th2 cells contrast with

Biological effects of Eosinophil mediators

a DTH (type IV) response which includes infiltration of macrophages and Th1 cells

Table 3 - Delayed hypersensitivity reactions Type Reaction time Clinical appearance Histology Antigen and site

contact

48-72 hr

eczema

lymphocytes, followed by macrophages; edema of epidermis

epidermal ( organic chemicals, poison ivy, heavy metals, etc.)

tuberculin

48-72 hr

local induration

lymphocytes, monocytes, macrophages

intradermal (tuberculin, lepromin, etc.)

granuloma

21-28 days

hardening

macrophages, epitheloid and giant cells, fibrosis

persistent antigen or foreign body presence (tuberculosis, leprosy, etc.)

Mekanisme perusakan melibatkan limfosit T dan monosit dan/atau makrofag Sel t sitotoksik (Tc) menyebabkan kerusakan langsung sedangkan sel T helper (TH1) mensekresi sitokin aktivasi Tc, makrofag serta monosit kerusakan

Diagnosis:
-

Mantoux test dan patch test

Terapi:
- Kortikosteroid dan agen imunosupresif

CAUSES

MECHANISM

PATHOPHYSIOLOGY

CLINICAL EXAMPLES Contact dermatitis Graft vs host reactions Viral infection Autoallergic disease

Antigen Tuberculin Poison Ivy Chemical Fungi Transplanted organs Virus

Sensitized Lymphocyte reacts with antigen

Release of : Lymphokines Migration inhibition factor Interferon Killer cells Transfer factor

Injury and destruction of target organ

Type IV hypersensitivity reaction

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