Cytotoxic Hypersensitivity (Type II)

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Presentation transcript:

Cytotoxic Hypersensitivity (Type II)

Type II Directed against cell surface or tissue antigen Cytotoxic hypersensitivity Reaction time is minutes to hours mediated by antibodies of IgM or IgG class and complement Phagocytes and NK cells may also play a role (ADCC). Diagnostic tests include detection of circulating antibody against tissues involved and the presence of antibody and complement in the lesion (biopsy) by immunofluorescence Directed against cell surface or tissue antigen The reaction may be local

Some diseases caused by Type II Transfusion reactions Autoimmune Hemolytic anemia Hemolytic disease of newborn Drug induced hemolytic anemia Autoimmune thrombocytopenia Pemphigus vulgaris(desmoglein ) Goodpastures syndrome Myasthenia gravis Graves disease Insulin resistant diabetes Pernicious anemia others

Drug-Induced Reactions: Adherence to Blood Components blood cell adsorbed drug or antigen drug metabolite antibody to drug complement Study Guide What is the hapten? What is the carrier? lysis

Drugs that can cause this type of hemolytic anemia include: Cephalosporins (a class of antibiotics) Levodopa Methyldopa Penicillin and its derivatives Quinidine Some nonsteroidal anti-inflammatory drugs (NSAIDs)

Hemolytic Disease of the Newborn first birth post partum subsequent RhD negative mother RhD positive red cells anti-RhD B cell Study Guide What immunoglobulin class(es)? Why is the second pregnancy at greater risk? Is there a problem in the second pregnancy is the fetus is Rh negative? Why? Lysis Of RBC’s RhD positive fetus RhD positive fetus anti-RhD

Type III (Immune complex mediated Diseases) كمپلكسهاي ايمني ممكن است متشكل از آنتي بادي هايي متصل شده به آنتي ژنهاي خودي و يا بيگانه باشند شماي پاتولوژيك اين بيماريها منعكس كننده محل رسوب اين كمپلكسها بوده و نه منشاء آنتي ژنها بنابراين اين بيماريها چندين بافت را ممكن است تحت تاثير قرار دهند در سال 1911دانشمندي بنام Von pirquet اولين بار اين بيماري را معرفي كرد

Type III (Immune complex mediated Diseases) The reaction may be general (e.g., serum sickness) or may involve individual organs including skin ( Arthus reaction), kidneys, lungs, blood vessels , joints or other organs. It is mediated by soluble immune complexes The reaction may take few hours after exposure to the antigen The lesion contains primarily neutrophils

Arthus reaction چنانچه آنتي ژني را زير جلدي به حيواني كه قبلا ايمن شده است تزريق كنيم آنتي باديهاي موجود در گردش با آنتي ژنهاي تزريق شده بسرعت متصل وكمپلكسهاي ايمني را تشكيل مي دهند. اين كمپلكسها در ديواره عروق كوچك در محل تزريق رسوب مي كنند كه منجر به واسكوليت موضعي و نكروز بافتي مي شود اين فرم واسكوليت موضعي را واكنش آرتوس مي نامند

Immune complex mediated diseases كمپلكسهاي ايمني در شرايط زير موجب بيماري مي شوند: ميزان زياد كمپلكس ها در صورتيكه اين كمپلكسها بطور موثرپاكسازي نشوند در بافت ها رسوب كنند ميزان رسوب كمپلكسها در بافتها بوسيله ماهيت كمپلكسهاوويژگيهاي عروق خوني تعيين مي شود كمپلكسهاي كوچك اغلب فاگوسيت نمي شوند وبيشتر از كمپلكسهاي درشت تمايل به رسوب در عروق دارند آنتي ژنهاي كاتيوني به تركيبات با بار منفي در غشاء پايه عروق خوني و گلومرولها يا مفاصل متصل مي شوند اين كمپلكسهاآسيب هاي بافتي شديدوطولاني ايجاد مي كنند

Tissue injury mechanisms Antibodies may opsonize cells or activate the complement system Production of complement proteins that opsonize cells. These cells are phagocytosed and destroyed by phagocytes that express FcR and CR Main mechanism in autoimmune hemolytic anemia and thrombocytopenia and hemolysis in transfusion reactions.

Tissue injury mechanisms آنتي باديهايي كه در بافت ها رسوب كرده اند با فعال كردن كمپلمان ،نوتروفيلها و ماكروفاژها را فراخوانده و سپس اين سلولها به آنتي باديها ويا پروتئينهاي كمپلمان متصل شده وفعال مي شوند. آنزيمهاي ليزوزومال و راديكالهاي آزاد از اين سلولهاي التهابي ترشح شده و موجب اسيب بافتي مي شوند.

Mechanisms of tissue injury

Tissue injury mechanisms آنتي باديهايي كه به گيرنده هاي طبيعي سلولها ويا ساير پروتئينهامتصل شده اندممكن است در عملكرد اين گيرنده ها و يا پروتئينها مداخله كرده و موجب بيماري شوند بدون اينكه باعث التهاب و يا آسيب بافتي شوند. اين مكانيسم علت بيماريهاي Grave و Myasthenia gravis است

آنتي باديهايي كه باعث بيماريهاي خاص سلولي و يا بافتي مي شوند معمولا اتوآنتي بادي هستند در بعضي شرايط آنتي بادي ممكن است عليه يك آنتي ژن خارجي (ميكروب) توليد شود ولي با تركيبات بافت خودي واكنش متقاطع دهد(cross reaction)

Some diseases caused by immune complexes Systemic Lupus Erythematosus Nephritis Vasculitis Post streptococcal glomerulonephritis

Mechanisms of tissue injury

Mechanisms of tissue injury

Pemphigus vulgaris