Professional Documents
Culture Documents
Hipersensitivity 200111
Hipersensitivity 200111
Hipersensitivity 200111
Definisi
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. H. G. Gell and Robin Coombs in 1963. Additional Type V
Comparison
Hypersensitivity Reactions
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
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
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
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
Systemic anaphylaxis
Allergen gets into the blood stream Dyspnea, BP, bronchole constriction, GI and bladder smooth muscle contration, shock, death within minutes if untreated Treatment - epinephrine
Inhaled allergen triggers reaction in nasal mucosa Watery exudate from nose, eyes, upper respiratory tract, sneeezing and coughing
Asthma Allergic asthma due to inhaled airborne allergens (pollens, dust, fumes, etc) Intrinsic asthma triggered by cold, exercise Reaction develops in lower respiratory tract Bronchoconstriction, airway edema, mucus secretion, inflammation Food allergies Ingestion of allergen Vomiting and diarrhea If allergens are absorbed into bloodstream, reactions can occur where allergen deposits
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)
Often occurs in young children Red skin rash Strong hereditary predisposition
Type I Hypersensitivity
Treatment
Avoid allergen if possible Antihistamines, or anti-prostaglandins Hyposensitization injections of low doses of allergen may cause a shift from IgE to IgG as the dominant antibody formed.
Type II Hypersensitivity
Antibody-mediated Cytotoxic HS
Antibodies (IgM or IgG) bind to cell surface antigens. Antigen/antibody complex may lead to:
These are normal reactions, but when they cause unwarranted tissue damage, they are considered a hypersensitivity.
Antigen terikat pada sel sasaran. Antibodi IgG dan IgM dengan adanya komplemen akan berikatan dengan antigen, sehingga dapat mengakibatkan hancurnya sel tersebut. Reaksi ini merupakan reaksi yang cepat.
Type II Hypersensitivity
Transfusion reactions
Hemolytic disease of the newborn (erythroblastosis fetalis) Drug-induced hemolytic anemia (penicillin)
Antibodi berikatan dengan antigen dan komplemen membentuk kompleks imun. Keadaan ini menimbulkan neuro-trophic chemotactic factor yang dapat menyebabkan terjadinya peradangan atau kerusakan lokal. Pada umumnya terjadi pada pembuluh darah kecil. Pengejawantahannya di kornea dapat berupa keratitis herpes simpleks, keratitis karena bakteri (stafilokok, pseudomonas) dan jamur.
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
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
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
Generalized reactions:
Reaksi terjadi melalui sel ketimbang melalui antobodi. Terdapat reaksi yang termasuk ke dalam hipersensitivitas IV ini, yaitu hipersensitivitas lambat dan sitotoksisitas diperantarai sel.
Type IV Hypersensitivity
TH cells that have been sensitized by an antigen develop a TH1 and (sometimes a TC response) leading to macrophage recruitment and activation. First noticed with reaction to tuberculosis bacteria (tuberculin reaction) Hallmarks of type IV is the large number of macrophages at the reaction site, and that it takes an average of 24 hrs to manifest after repeat exposure.
Type V : Hypersensitivity
Inflammation
Inflamasi
Reaksi lokal pada jaringan karena adanya injuri. Reaksi proteksi komples Penyebab : berbagai stimulus exogen / endogen Agen penyebab : dihancurkan oleh tubuh
Mechanisme
Classification
1. alterative (predominance of necrosis - diphtheria) 2. exsudative (pleuritis) 3. proliferative (cholecystitis - thickening of the wall by fibrous tissue)
Classification
nonspecific (not possible to trace the etiology) - vast majority specific (e.g. TB)
aseptic (sterile) - chemical substances, congelation, radiation - inflammation has a reparative character septic (caused by living organisms) - inflammation has a protective character
Acute inflammation
important role in inflammation has microcirculation! supply of white blood cells, interleukins, fibrin, etc.
Local symptomatology
classical 5 symptoms (Celsus 1st c. B.C., Virchow 19th c. A.D.) 1. calor - heat 2. rubor - redness 3. tumor - swelling 4. dolor - pain 5. functio laesa - loss (or impairment) of function
Systemic symptomatology
leucopenia
Vascular changes
vasodilation
increased permeability of vessels due to widened intercell. junctions and contraction of endothelial cells (histamin, VEGF, bradykinin)
protein poor transudate (edema) protein rich exsudate leukocyte-dependent endothelial injury
Cellular events
neutrophils (1-2 days) monocytes (2-3 days) endogenous signaling molecules - lymphokines exogenous - toxins
chemotaxis
phagocytosis - lysosomal enzymes, free radicals, oxidative burst passive emigration of RBC - no active role in inflamm. - hemorrhagic inflammation
Phagocytosis
adhesion and invagination into cytoplasm engulfment lysosomes - destruction in highly virulent microorganisms can die leucocyte and not the microbe in highly resistant microorganisms persistence within macrophage - activation after many years
chemical substances neutralization normalization of vasc. permeability apoptosis of inflammatory cells lymphatic drainage
tissue destruction fibrinous inflammtion purulent infl. abscess formation (pus, pyogenic membrane, resorption - pseudoxanthoma cells - weeks to months)
2. healing by scar
Chronic inflammation
reasons:
persisting infection or prolonged exposure to irritants (intracell. surviving of agents - TBC) repeated acute inflamations (otitis, rhinitis) primary chronic inflammation - low virulence, sterile inflammations (silicosis) autoimmune reactions (rheumatoid arthritis, glomerulonephritis, multiple sclerosis)
Chronic inflammation
lymphocytes plasma cells monocytes/macrophages activation of macrophages by various mediators - fight against invaders
lymphocytes plasma cells, cytotoxic (NK) cells, coordination with other parts of immune system plasma cells - production of Ig monocytes-macrophages-specialized cells (siderophages, gitter cells, mucophages)
1. alterative 2. exsudative
2a. serous 2b. fibrinous 2c. suppurative 2d. pseudomembranous 2e. necrotizing, gangrenous primary (rare) x secondary (cholecystitis)
3. proliferative
2a. serous - excessive accumulation of fluid, few proteins - skin blister, serous membranes - initial phases of inflamm. modification - catarrhal - accumulation of mucus 2b. fibrinous - higher vascular permeability exsudation of fibrinogen -> fibrin - e.g. pericarditis (cor villosum, cor hirsutum - "hairy" heart fibrinolysis resolution; organization fibrosis scar
2c. suppurative (purulent) - accumulation of neutrophillic leucocytes - formation of pus (pyogenic bacteria) interstitial
acute border surrounding tissue chronic border - pyogenic membrane Pseudoabscess pus in lumen of hollow organ
formation of suppurative fistule accumulation of pus in preformed cavities empyema (gallbladder, thoracic)
bacteremia (no clinical symptoms!; danger of formation of secondary foci of inflamm. (endocarditis, meningitis) sepsis (= massive bacteremia) - septic fever, activation of spleen, septic shock thrombophlebitis - secondary inflammation of wall of the vein with subsequent thrombosis - embolization pyemia - hematogenous abscesses (infected infarctions) lymphangiitis, lymphadenitis
2d. pseudomembranous - fibrinous pseudomembrane (diphtheria - Corynebacterium, dysentery - Shigella) - fibrin, necrotic mucosa, etiologic agens, leucocytes 2e. necrotizing - inflammatory necrosis of the surface - ulcer (skin, gastric)
gangrenous - secondary modification by bacteria - wet gangrene - apendicitis, cholecystitis - risk of perforation - peritonitis
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)
Granulomatous inflammation
1. Bacteria
4. Foreign body
5. Unknown - sarcoidosis