FACULTY OF MEDICINE MALANG ISLAMIC UNIVERSITY SKIN TEST Applying the tuberculin skin test Courtesy of Dr. Marc Steben 2 The MTCT-Plus Initiative Applying the tuberculin skin test 3 The MTCT-Plus Initiative Applying the tuberculin skin test Courtesy of Dr. Marc Steben 4 The MTCT-Plus Initiative Reading the tuberculin skin test Read 2-3 days after placing the test Feel for induration Color change without induration is not included in the measurement Use a ruler or calipers Have someone else check if unsure Always document the exact size (mm) – not just “positive” or “negative” 5 The MTCT-Plus Initiative Reading the tuberculin skin test Courtesy of Dr. Marc Steben 6 The MTCT-Plus Initiative Reading the tuberculin skin test 7 The MTCT-Plus Initiative YY REAKSI HIPERSENSITIVITAS 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 bronchoconstriction, mucus secretion, vasodilatation, vascular permeability tryptase proteolysis kininogenase kinins and vasodilatation, vascular permeability, edema ECF-A (tetrapeptides) attract eosinophil and neutrophils Newly formed mediators leukotriene B4 basophil attractant leukotriene C4, D4 same as histamine but 1000x more potent prostaglandins D2 edema and pain PAF 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 Allergen interacts with IgE on mast cell PATHOPHYSIOLOGY Release of chemical mediators : Histamine SRS-A Kinins Prostaglandins Capillary dilation Increased Capillary permebiality Increased Blood Volume Exudation of Cell, fluid protein Pressure of exudate Nerve irritation Constriction of smooth muscle Type I hypersensitivity reaction 23 MANIFESTATIONS Respiratorytract tract Respiratory 1.1. Upper headache” Upper“sinus “sinus headache” itching itchingofofeyes eyes tearing, tearing,sneezing, sneezing, watery nasal discharge, watery nasal discharge, itching of nose, itching of nose, throat irritation throatwheezing, irritation dyspnea, 2. Lungs 2. dry Lungs wheezing, cough, tightness dyspnea, in chest dry cough, tightness 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 Asthma Food allergies Atopic dermatitis Urticaria Type I hypersensitivity reaction (continued) 24 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 PATHOPHYSIOLOGY MECHANISM 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 Thrombocytopenia Vasculitis CLINICAL EXAMPLES Hemolytic anemia Susceptability to infections Purpura Vesicular purpura Type II hypersensitivity reaction 28 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 Type III hypersensitivity reactions (Arthus Reaction) - Ab-Ag Complexes Critical mediators appear to be C5a-receptor and FcgRIII--probably present on mast cells CAUSES MECHANISM PATHOPHYSIOLOGY Antigen Autoantibodies Drugs Serum Chemicals Foreign antigen Bacteria Virus Antigen and antibody form an immune complex Deposits on vessel walls or basement membrane Tissue destruction Inflammation CLINICAL EXAMPLES Glomerulonephritis Vasculitis Arthus reaction Rheumatoid diseases Serum sickness Type III hypersensitivity reaction 31 Biopsi jaringan (endapan Ig dan komplemen) Kompleks imun pada darah dan penurunan Diagnosis: 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 Biological effects of Late stage of an allergicmediators response includes the Eosinophil recruitment of eosinophils and Th2 cells contrast with a DTH (type IV) response which includes infiltration of macrophages and Th1 cells Table 3 - Delayed hypersensitivity reactions Type contact tuberculin granuloma Reaction time 48-72 hr 48-72 hr 21-28 days Clinical appearance Histology Antigen and site eczema lymphocytes, followed by macrophages; edema of epidermis epidermal ( organic chemicals, poison ivy, heavy metals, etc.) local induration lymphocytes, monocytes, macrophages intradermal (tuberculin, lepromin, etc.) macrophages, epitheloid and giant cells, fibrosis persistent antigen or foreign body presence (tuberculosis, leprosy, etc.) hardening 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 Antigen Tuberculin Poison Ivy Chemical Fungi Transplanted organs Virus Sensitized Lymphocyte reacts with antigen PATHOPHYSIOLOGY Release of : Lymphokines Migration inhibition factor Interferon Killer cells Transfer factor Injury and destruction of target organ CLINICAL EXAMPLES Contact dermatitis Graft vs host reactions Viral infection Autoallergic disease Type IV hypersensitivity reaction 37