Lec 57: Introduction to Hypersensitivity Flashcards
Type I (immediate) hypersensitivity
IgE antibody-mediated activation of mast cells (effector cells) produces an inflammatory reaction. IgE antibody production (sensitization), mast cell activation (re-exposure).
Sensitization
allergens are first processed by APCs. APCs interact with CD4 Th2 cells, causing interleukins to stimulate B-cell maturation. IL-4 causes plasma cells to switch from IgM to IgE synthesis. IL-5 stimulates the production and activation of eosinophils.
Re-exposure
allergen-specific IgE antibodies are bound to mast cells. allergens cross-link IgE antibodies specific for the allergen on mast cell membranes. IgE triggering causes mast cell release of preformed mediators (1. early phase reaction with release of histamine, chemotactic factors for eosinophils, proteases. 2. produces tissue swelling and bronchoconstriction). late phase reaction (1. mast cells synthesize and relase prostaglandins and leukotrienes. 2. enhances and prolongs acute inflammatory reaction).
Type II hypersensitivity
antibody-dependent reactions
Complement-dependent reactions
lysis (IgM-mediated), lysis (IgG-mediated), phagocytosis
Lysis (IgM-mediated)
antibody (IgM) directed against antigen on the cell membrane activates the complement stem, leading to the lysis of yhe cell by the membrane attack complex (MAC). ex: IgM types of cold immune hemolytic anemias, transfusion of group A blood (contains anti-B-IgM antibodies) into a group B individual
Lysis (IgG-mediated)
IgG attaches to basement membrane/matrix–>activates complement system–>C5a is produced (chemotactic factor)–>recruitment of neutrophils/monocytes to the activation site–>release of enzymes, reactive oxygen species–>damage to tissue. ex: goodpasture’s syndrome with IgG antibodies directed against pulmonary and glomerular capillary basement membranes, acute rheumatic fever with IgG antibodies directed against antigens in hear, skin, brain, subcutaneous tissue, joints.
Phagocytosis
fixed macrophages (eg. in spleen) phagocytose hematopoietic cells (eg. RBCs) coated by IgG antibodies or complement (C3b). ex: warm (IgG) immune hemolytic anemia, ABO hemolytic disease of the newborn (group O mother jas anti-A, B-IgG antibodies that cross the placenta and attach to getal blood group A or B RBCs)
Complement-independent reactions
antibody (IgG)-dependent cell mediated cytotoxicity, antibody (IgE)-dependent cell-mediated cytotoxicity, IgG autoantibodies directed against cell surface receptors–>impair function of the receptor (eg. anti-Ach receptor antibodies in myasthenia gravis) or stimulate function (eg. anti-TSH receptor antibodies in Graves’ disease).
Antibody (IgG)-dependent cell-mediated cytotoxicity
cells are coated by IgG–>leukocytes (neutrophils, monocyte, NK cells) bind to igG–>activated cells release inflammatory mediators causing lysis of teh cells. ex: killing virus-infected cells or tumor cells
Antibody (IgE)-dependent cell-mediated cytotoxicity
helminth in tissue is coated by IgE antibodies–>eosinophil IgE receptors attach to IgE–>eosinophils release major basic protein, which kills the helminth
Tests used to evaluated type II hypersensitivity
direct Coombs’ test detects IgG and C3b attached to RBCs. Indirect Coombs’ test detects antibodies (eg. anti-D) in serum
Type III hypersensitivity
activation of teh complement system by circulating antigen-antibody complexes (eg. DNA-anti-DNA complexes). first exposure to antigen–>synthesis of antibodies. second exposure to antigen–>deposition of antigen-antibody complexes, complement activation, producing C5a, which attracts neutrophils that damage tissue. Arthus reaction
Arthus reaction
localized immunocomplex reaction. ex: farmer’s lung from exposure to thermophilic actinomycetes, or antigens, in air.
Type IV hypersensitivity
antibody-independent T cell-mediated reactions (cellular-mediated immunity, CMI)
Functions of CMI
control of infections caused by viruses, fungi, helminths, mycobacteria, intracellular bacterial pathogens. graft rejection. tumor surveillance
types of reactions
delayed reaction hypersensitivity (DRH), cell-mediated cytotoxicity
Delayed reaction hypersensitivity (DRH)
CD4 cells interact with macrophages (APCs with MHC class II antigens), resulting in cytokine injury to tissue
Cell-mediated cytotoxicity
CD8 T cells interact with altered MHC class I antigens on neoplastic, virus-infected or donor graft cells, causing cell lysis. contact dermatitis–activated CD4 and CD8 T cells damage antigens in skin (eg. poison ivy, nickel)
Type I Hypersensitivity
IgE-dependent activation of mast cells.
Atopic disorders: hay fever, eczema, hives, asthma, reaction to bee sting.
Drug hypersensitivity: penicillin rash or anaphylaxis
Type II Hypersensitivity
Antibody-dependent reaction.
Complement-dependent reactions
Lysis (IgM mediated): ABO mismatch, cold immune hemolytic anemia;
Lysis (IgG mediated): Goodpasture’s syndrome, Pernicious anemia;
Phagocytosis: warm (IgG) autoimmune hemolytic anemia, ABO and Rh hemolytic disease of newborn, idiopathic thrombocytopenic purpura.
Complement-independent reactions
Antibody (IgG)-dependent cell-mediated cytotoxicity: natural killer cell destruction of neoplastic and virus-infected cells; Antibody (IgE)-dependent cell-mediated cytotoxicity: eosinophil destruction of helminths; Antibodies directed against cell surface receptors: myasthenia gravis, Graves’ disease
Type III
Deposition of antigen-antibody complexes. Systemic lupus erythematosus (DNA-anti-DNA), Serum sickness (horse antithymocyte globulin-antibody), Poststreptococcal glomerulonephritis
Type IV
Antibody-independent T cell-mediated reactions. Delayed type–tuberculous granuloma; PPD reaction, Multiple sclerosis. Cell-mediated cytotoxicity–killing of tumor cells and virus-infected cells; contact dermatitis (e.g., poison ivy, nickel)
Innate (natural, nonspecific) immunity
nonspecific defense system against microbial pathogens. does NOT confer long-lasting immunity against pathogens