Hypersensitivity ReactionDefinisi Reaksi imunologik (humoral atau diperantarai seluler) terhadap antigen, baik yang bersumber endogen maupun eksogen, dapat menyebabkan beberapa reaksi perusakan jaringan. Classification The four-group classification was expounded by P. Additional Type V . G. H. Gell and Robin Coombs in 1963. Comparison . II and III are “immediate” Type IV is delayed .Hypersensitivity Reactions Gell and Coombs classification: Type I – IgE mediated (allergy) Type II – Antibody-mediated cytotoxic Type III – Immune Complex mediated Type IV – Delayed-Type Hypersensitivity (DTH) Type V – Autoimmune Disseases Types I. Type I Hypersensitivity Antigens are called “allergens” Unknown why people get allergies, but there is a strong genetic predisposition (called atopy) Hallmark is inappropriate production of IgE against allergens that cause mast cell degranulation Normally IgE/mast cell activity should be directed against parasitic infections Type I Hypersensitivity Mediators of Type I hypersensitivites Mast cell granule contents (early effects) Histamine and Heparin - ↑ vascular permeability, smooth muscle contraction (intestines, bronchi), mucus secretion Chemotactic factors – attract eosinophils and neutrophils Proteases – mucus secretion, complement activation, degradation of blood vessel basement membrane Leukotrienes and prostaglandins – secreted after tissue disruption caused by mast cell degranulation, effects are similar to histamine Arrival of proinflammatory eosinophils and neutrophils Later Effects Reaksi Hipersensitivitas Tipe I ( Tipe Anafilaksis ) Rx hipersensitivitas tipe cepat IgE Co : asma, rinitis, dermatitis atopi, urtikaria, anafilaksis. Ag sel B untuk membentuk Ig E dengan bantuan sel Th. Ig E diikat oleh mastosit pd reseptor Fc. Bila terpajan ulang, maka Ag tersebut IgE yang sudah ada pada permukaan mastosit degranulasi mastosit histamin. . . . upper respiratory tract.Clinical Manifestations of Type I Systemic anaphylaxis Allergen gets into the blood stream Dyspnea. death within minutes if untreated Treatment . eyes. ↓BP. sneeezing and coughing Allergic rhinitis (hay fever) . bronchole constriction. shock.epinephrine Inhaled allergen triggers reaction in nasal mucosa Watery exudate from nose. GI and bladder smooth muscle contration. reactions can occur where allergen deposits asthma-like symptoms Urticaria (hives. dust.Clinical Manifestations of Type I Asthma Allergic asthma – due to inhaled airborne allergens (pollens. inflammation Food allergies Ingestion of allergen Vomiting and diarrhea If allergens are absorbed into bloodstream. exercise Reaction develops in lower respiratory tract Bronchoconstriction. fumes. mucus secretion. etc) Intrinsic asthma – triggered by cold. airway edema. wheal & flare response) . . Triad asma Hipertrofi muscularis bronchial (1) spasme bronchial Produksi mukus berlebihan (2) obstruksi alveoli tertutup emphysema Edema membran mukus (3) infiltrasi eosinofil mediator inflamasi membran edema kristalisasi enzym eosinofil diamond-shaped CharcotLeyden crystals (4) . Clinical Manifestations of Type I Atopic Dermatitis (allergic eczema) Often occurs in young children Red skin rash Strong hereditary predisposition . . . . or anti-prostaglandins Hyposensitization – injections of low doses of allergen may cause a shift from IgE to IgG as the dominant antibody formed.Type I Hypersensitivity Treatment Avoid allergen if possible Antihistamines. . they are considered a hypersensitivity. but when they cause unwarranted tissue damage.Type II Hypersensitivity Antibody-mediated Cytotoxic HS Antibodies (IgM or IgG) bind to cell surface antigens. Antigen/antibody complex may lead to: Complement activation lysis ADCC Opsonization phagocytosis These are normal reactions. . Antibodi IgG dan IgM dengan adanya komplemen akan berikatan dengan antigen. Reaksi ini merupakan reaksi yang cepat.Reaksi Hipersensitivitas Tipe II ( Tipe Sitotoksik) Antigen terikat pada sel sasaran. sehingga dapat mengakibatkan hancurnya sel tersebut. . . . . Type II Hypersensitivity Examples of Type II HS: Transfusion reactions To ABO blood groups To other RBC blood groups Hemolytic disease of the newborn (erythroblastosis fetalis) Drug-induced hemolytic anemia (penicillin) . Keadaan ini menimbulkan neuro-trophic chemotactic factor yang dapat menyebabkan terjadinya peradangan atau kerusakan lokal.Reaksi Hipersensitivitas Tipe III (diperantarai kompleks imun) Antibodi berikatan dengan antigen dan komplemen membentuk kompleks imun. Pengejawantahannya di kornea dapat berupa keratitis herpes simpleks. Pada umumnya terjadi pada pembuluh darah kecil. . keratitis karena bakteri (stafilokok. pseudomonas) dan jamur. Type III Hypersensitivity Immune Complex Disease Antibody (IgG) / attaching to soluble antigen leads to complex formation Immune complexes may deposit in: Blood vessel walls (vasculitis) Synovial joints (arthritis) Glomerular basement membrane (glomerulonephritis) Choroid plexus . Type III Hypersensitivity Damage occurs due to: Anaphylatoxin release due to complement activation (C3a. C5a) which then attracts neutrophils. and causes mast cell degranulation Neutrophils have trouble phagocytosing “stuck” immune complexes so they release their granule contents leading to more inflammation Platelet aggregation also results from complement activation These effects are also known as the Arthus reaction . “farmer’s lung” from inhaling particles from moldy hay .g.Type III Hypersensitivity Localized reactions edema and redness (erythema) and tissue necrosis of the affected tissue Can occur in the skin following insect bites Can occur in the lungs E. . malaria. hepatitis. mono etc.Type III Hypersenstivity Generalized reactions: Serum sickness (following treatment with antiserum to a toxin) Autoimmune diseases SLE Rheumatoid arthritis Drug reactions (penicillin) Infectious diseases Meningitis. . . . . yaitu hipersensitivitas lambat dan sitotoksisitas diperantarai sel. .Reaksi Hipersensitivitas Tipe IV (diperantarai sel) Reaksi terjadi melalui sel ketimbang melalui antobodi. Terdapat reaksi yang termasuk ke dalam hipersensitivitas IV ini. and that it takes an average of 24 hrs to manifest after repeat exposure. First noticed with reaction to tuberculosis bacteria (tuberculin reaction) Hallmarks of type IV is the large number of macrophages at the reaction site.Type IV Hypersensitivity Delayed type hypersensitivity (DTH) TH cells that have been “sensitized” by an antigen develop a TH1 and (sometimes a TC response) leading to macrophage recruitment and activation. . . . . . . Type V : Hypersensitivity . . Inflammation . Reaksi proteksi komples Penyebab : berbagai stimulus exogen / endogen Agen penyebab : dihancurkan oleh tubuh .Inflamasi Reaksi lokal pada jaringan karena adanya injuri. . alteration 2. exsudation . proliferation (pembentukan granulasi dan jaringan fibrosa) .Mechanisme local systemic 3 major: 1.inflammatory exsudate liquid (exsudate) cellular (infiltrate) 3. alterative (predominance of necrosis .Classification several points of view length: acute × chronic (+ subacute. hyperacute) according to predominant component 1.diphtheria) 2. proliferative (cholecystitis . exsudative (pleuritis) 3.thickening of the wall by fibrous tissue) . inflammation has a reparative character septic (caused by living organisms) .vast majority specific (e.g.chemical substances. congelation. TB) according to causative agent aseptic (sterile) .Classification according to histological features nonspecific (not possible to trace the etiology) .inflammation has a protective character . radiation . . fibrin. etc.Acute inflammation important role in inflammation has microcirculation! supply of white blood cells. interleukins. heat 2. A..redness 3. B.Local symptomatology classical 5 symptoms (Celsus 1st c. functio laesa . Virchow 19th c. rubor . calor .C.swelling 4.) 1.pain 5.loss (or impairment) of function . dolor . tumor .D. increased level of some substances (C-reactive protein) .Systemic symptomatology fever (irritation of centre of thermoregulation) TNF. IL-1 IL-6 – high erythrocyte sedimentation rate bacteria – neutrophils parasites – eosinophils viruses .increased number of WBC leucopenia immunologic reactions . rickettsiosis leucocytosis . salmonella infections.lymphocytosis viral infections. junctions and contraction of endothelial cells (histamin. bradykinin) protein poor transudate (edema) protein rich exsudate leukocyte-dependent endothelial injury proteolysis – protein leakage platelet adhesion thrombosis .Vascular changes vasodilation increased permeability of vessels due to widened intercell. VEGF. Cellular events leukocytes margination rolling adhesion transmigration emigration of: neutrophils (1-2 days) monocytes (2-3 days) endogenous signaling molecules .no active role in inflamm. oxidative burst passive emigration of RBC . free radicals.lymphokines exogenous .toxins chemotaxis phagocytosis . .hemorrhagic inflammation .lysosomal enzymes. destruction in highly virulent microorganisms can die leucocyte and not the microbe in highly resistant microorganisms persistence within macrophage .Phagocytosis adhesion and invagination into cytoplasm engulfment lysosomes .activation after many years . resolution . pyogenic membrane.restoration to normal. permeability apoptosis of inflammatory cells lymphatic drainage tissue destruction fibrinous inflammtion purulent infl. abscess formation (pus.pseudoxanthoma cells .Outcomes of acute inflammation 1. progression into chronic inflammation .weeks to months) 2. limited injury chemical substances neutralization normalization of vasc. healing by scar 3. resorption . low virulence.TBC) repeated acute inflamations (otitis. surviving of agents . sterile inflammations (silicosis) autoimmune reactions (rheumatoid arthritis. glomerulonephritis. rhinitis) primary chronic inflammation . multiple sclerosis) .Chronic inflammation reasons: persisting infection or prolonged exposure to irritants (intracell. cytotoxic (NK) cells. gitter cells.production of Ig monocytes-macrophages-specialized cells (siderophages. mucophages) . coordination with other parts of immune system plasma cells .fight against invaders lymphocytes plasma cells.Chronic inflammation chronic inflammatory cells ("round cell" infiltrate) lymphocytes plasma cells monocytes/macrophages activation of macrophages by various mediators . proliferative . gangrenous primary (rare) x secondary (cholecystitis) 3. pseudomembranous 2e.Morphologic patterns of inflammation 1. alterative 2. fibrinous 2c. exsudative 2a. necrotizing. suppurative 2d. serous 2b. serous membranes .g.accumulation of mucus 2b.initial phases of inflamm. pericarditis (cor villosum. few proteins . modification . fibrinous .higher vascular permeability exsudation of fibrinogen -> fibrin ."hairy" heart fibrinolysis resolution.catarrhal . serous . cor hirsutum . organization fibrosis scar .e.skin blister.excessive accumulation of fluid.Morphologic patterns of inflammation 2a. localized collection acute – border – surrounding tissue chronic – border . thoracic) . 2c. suppurative (purulent) .pyogenic membrane Pseudoabscess – pus in lumen of hollow organ formation of suppurative fistule accumulation of pus in preformed cavities empyema (gallbladder.formation of pus (pyogenic bacteria) interstitial phlegmone – diffuse soft tissue abscess .accumulation of neutrophillic leucocytes . meningitis) sepsis (= massive bacteremia) . lymphadenitis . danger of formation of secondary foci of inflamm. complications of suppurative inflamm.septic fever. septic shock thrombophlebitis .hematogenous abscesses (infected infarctions) lymphangiitis.embolization pyemia .secondary inflammation of wall of the vein with subsequent thrombosis . activation of spleen.: bacteremia (no clinical symptoms!. (endocarditis. leucocytes 2e. cholecystitis .Shigella) .inflammatory necrosis of the surface . etiologic agens.fibrinous pseudomembrane (diphtheria .ulcer (skin. pseudomembranous .secondary modification by bacteria . gastric) gangrenous . necrotic mucosa. necrotizing .apendicitis. 2d. dysentery .peritonitis .fibrin.wet gangrene .Corynebacterium.risk of perforation . Granulomatous inflammation distinctive chronic inflammation type cell mediated immune reaction (delayed) aggregates of activated macrophages epithelioid cell multinucleated giant cells (of Langhans type x of foreign body type) NO agent elimination but walling off intracellulary agents (TBC) . Unknown . Foreign body 5. breast prosthesis 4. Inorganic metals or dust silicosis berylliosis suture (Schloffer „tumor“). Bacteria TBC leprosy syphilis (3rd stage) 2. Parasites + Fungi 3.sarcoidosis .Granulomatous inflammation 1.