type ii
DESCRIPTION
Type II. 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 - PowerPoint PPT PresentationTRANSCRIPT
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Type II•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
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Clinical Examples• 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
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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)
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Type III
• 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.
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Type III
• It is mediated by soluble immune complexes
• The reaction may take few hours after exposure to the antigen
• The lesion contains primarily neutrophils
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Immune complex mediated diseases
• Immune complexes cause disease only:1-in excessive amounts2- not efficiently cleared3- become deposited in tissuesa) intermediate complexes tend to be deposited
in vesselsb) Cationic antigens bind to negatively charged
components of the basement membranes of blood vessels and glomeruli,joints
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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.
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Cell Mediated Immunity
• The effector cells involved in these processes are cytotoxic T-lymphocytes (CTLs), NK-cells and Th cells
Phagocytosis and killing of intracellular pathogens Direct cell killing by cytotoxic T cells Direct cell killing by NK and K cells • These responses are especially important for
destroying intracellular bacteria, eliminating viral infections and destroying tumor cells
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• Response to microbes residing within the phagosomes is mediated by effector CD4 Th1 cells
• Microbes that infect and replicate in nonphagocytic cells,is mediated by CD8
• T cell dependent macrophage activation and inflammation may damage normal tissues
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• Th1(IFN- )• Th2(IL-4,IL-5)• Th17(TGF-,IL-1,IL-6)• The most differentiation –inducing stimuli
are IFN- ,IL-12 and IL-4
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Killing by cytotoxic T cells
• release some substances known as perforin ,Granzyme A,B ,C and serglycin and granulysin
• the CTL may release lymphokines and/or cytokines
•
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• Recognition• Activation• Lethal hit• Release(cathepsin B)
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Type IV hypersensitivity
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Type IV hypersensitivity• DTH (Delayed type hyper sensitivity)• Is a T cell mediated inflammatory response ,in which
stimulation of T cells leads to macrophage activation and localised inflammation and edema within tissues.
• This effector T cell response is essential for the control of intracellular and other pathogens.
• If the response is excessive it can damage host tissues• Subsequent exposure of the sensitised individual to the
exogenous Ag results in the recruitment of specific T cells to the site and development of a local inflammatory response over 24-72 hrs.
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Interferon production
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TDTH formation
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variants of type IV HS
There are 3 variants of type IV HS reaction• Contact HS• Tuberculin type HS• Granulomatous HS
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Contact hypersensitivity
• Occur within 72 hrs of Ag challenge• Characterized by an eczematous reaction
in the skin at the point of contact with an allergen
• Organic chemicals and inorganic metals such as nickel , chromate and rubber accelerator in latex gloves
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Contact hypersensitivity
Has 2 stage• Sensitization • elicitation
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TUBERCULIN TYPE
• Is induced by soluble antigens from organisms such as M.Tuberculosis and Leprae and leishmania tropica
• Following ID tuberculin challenge memory T cells are recruited and activated to secrete IFN- ,which activates Macrophages to produce TNF and IL-1
• The initial influx at 4 hrs is neutrophils but replaced at 12 hrs by monocytes and T cells.
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PPD skin test
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Granulomatous HS
• Clinically the most important form of type IV HS.
• If the Ag persist(intracellular micro.,other particles such as ziconium and beryllium ,talc ,silica) ,chronic activation of T cells and macrophages lead to granuloma formation and tissue damage.
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Granulomatous HS
The Granuloma contains :• Epithelioid cells (secret TNF)• Langhans giant cells(low ER and
degeneration of lysosomes and mitochondria)
• MacrophagesIFN- and TNF are essential for granuloma
formation
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Granulomatous HS
• Crohn disease(chronic inflammatory disease of ileum and colon)
• Leishmaniasis• Sarcoidosis• Leprosy• tuberculosis