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24 Cards in this Set
- Front
- Back
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Immediate (type I) hypersensitivity disorder
Mechanism and Pathologic lesions |
- commonly called allergies
- activation of Th2 subset of CD4+ T cells by environmental antigens --> IgE production --> IgE binds antigen --> mast cells release vasoactive amines and other mediators that transiently affect vascular permeability and induce smooth muscle contraction in various organs Lesions = vascular dilation, edema, smooth muscle contraction, mucus production, and inflammation |
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What cytokines secreted by Th2 cells contribute to the reactions of Immediate (type I) hypersensitivity disorder?
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1. IL-4 --> stimulates B cells specific for allergen to undergo H chain class switching to IgE and to secrete this isotype
2. IL-5 --> activates eosinophils that are recruited to reaction 3. IL-13 --> acts on epithelial cells and stimulates mucus secretion |
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What chemokine is responsible for recruiting Th2 cells to site of allergic reactions
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eotaxin (also recruits eosinophils)
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Fc-epsilon-RI (what cells express it?)
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- high affinity receptor for the Fc portion of the epsilon heavy chain of IgE
Cells that express it 1. mast cells --> important in allergic reaction; affinity of mast cell receptor so high that is always occupied by IgE 2. basophils 3. eosinophils --> often present in hypersensitivity rxns and have role in IgE-mediated host defense against helminths |
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What types of mast cell granule contents may be released in allergic reaction?
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1. histamine --> vasodilation, increased vascular permeability, smooth muscle contraction, and increased mucus secretion
2. adenosine --> bronchoconstriction and inhibits platelet aggregation 3. chemotactic factors for neutrophils and eosinophils **#'s 1-3 are often released rapidly** 4. neutral proteases (ex. tryptase) --> may damage tissues, generate kinins, and cleave complement components 5. acidic proteoglycans (heparin, chondroitin sulfate) --> storage matrix for vasoactive amines |
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what types of mediators are released by mast cells in allergic rxns (type I hypersensitivity)
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1. vasoactive amines from granule stores (histamine, adenosine) as well as chemotactic factors for neutrophils and eosinophils
2. Lipid mediators (PGD2,LTC4 LTD4, LTB4) 3. Cytokines (TNF and chemokines, IL-4 AND IL-5, IL-13) - cytokines important for late-phase reaction |
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What are the 2 well defined phases of the IgE-triggered allergic reaction and what are they characterized by?
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1. Immediate response (w/in 5-30 minutes of exposure, and subsiding by 1hr)
- vasodilation, vascular leakage, smooth muscle spasm 2. Late-Phase Response (w/in 2-8 hrs, and may last several days) - inflammation and tissue destruction - dominant cells = neutrophils, eosinophils, and lymphocytes (esp Th2 cells) |
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What contribution do eosinophils have to the immediate hypersensivity (type I) disorder?
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important effectors of tissue injury in late-phase response
- major basic protein and eosinophil cationic protein --> toxic to epithelial cells - LTC4 and platelet activiating factor --> promote inflammation |
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what are the actions of the lipid mediators from mast cells?
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1. PGD2 --> intense bronchospasm and increased mucus secretion
2. LTC4 and LTD4 --> several times more active than histamine in increasing vascular permeability and causing bronchial smooth muscle contraction 3. LTB4 --> highly chemotactic for neutrophils, eosinophils, and monocytes |
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What is the sequence of cellular responses in Immediate Hypersensitivity (type I)?
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1. activation of Th2 cells --> IgE class switching in heavy chain of B cells (so they secrete IgE now)
2. IgE production 3. Binding of IgE to FcERI on mast cells --> mast cell sensitization 4. Repeat exposure to allergen 5. Activation of mast cells --> release of mediators a. immediate response --> vasoactive amines and lipid mediators b. Late phase --> due to cytokine synthesis and secretion by mast cells (synth takes a while, then actions of cytokines to recruit other inflamm cells, which takes some time, is what's resp. for late-phase response) |
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What determines whether an allergic reaction will be systemic or local?
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the route of antigen exposure
1. systemic --> due to systemic (parenteral) administration of a protein antigen or drugs ex) bee sting or administration of a drug the patient is allergic to 2. Local --> when antigen confined to particular site ex.) skin, GI tract (eating something you're allergic to), lung (inhalation of allergen) |
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What are the clinical manifestations of a systemic allergic reaction?
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1. itching, hives, skin erythema
2. respiratory difficulty (due to pulmonary bronchoconstriction, and exacerbated by hypersecretion of mucus) 3. laryngeal edema may cause upper airway obstruction - GI tract musculature may be affeted --> vomiting, abdominal cramps, diarrhea 4. Systemic vasodilation w/ fall in BP (anaphylactic shock) 5.Circulatory collapse and death |
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atopy
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term used to imply familial disposition to localized Type I hypersensitivity reactions
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why is splenectomy of some benefit to patients w/ hemolytic anemia or autoimmune thrombocytopenia?
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opsonized cells are usually eliminated in spleen
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What are the different mechanisms by which antibodies cause disease in Type II Hypersensitivity?
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1. opsonization of circulating cells by binding autoantibodies --> makes them targets for phagocytosis
- phagocytes express receptors for Fc tails of IgG antibodies and for breakdown products of C3 complement protein 2. Inflammation - antibodies bound to cell/tissue antigens activate complement system via "classical pathway" --> complement products recruit neutrophils and moncytes 3. Antibody-mediated cellular dysfunction --> antibodies may simply impair or dysregulate cell fucntion w/o causing injury or inflammation (ex. myasthenia gravis or graves disease) |
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what is the morphologic appearance of immune complex injury (type III hypersensitivity)?
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- acute necrotizing vasculitis, microthrombi, superimposed ischemic necrosis accompanied by acute inflammation of affected organs
- fibrinoid necrosis of vessel wall --> smudgy eosinophilic appearance |
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what are the phases in induction of systemic immune complex-mediated disease (type III hypersensitivity)?
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1. Specific antibodies produced w/in 5 days of antigen exposure, and form Ag-Ab responses in circulation
2. Complexes leave circulation and deposit in various tissues 3. Inflammatory reaction in tissue(s) - complexes activate complement system --> release bioactive fragments (C3a and C5a) --> increase vascular permeability and chemotactice for neutrophils and monocytes - complexes bind Fcgamma receptors on neutrophils and monocytes (activate them) - secretion of add'l proinflamm substances by leukocytes --> damage tissues - complexes cause platelet aggregation and activate Hageman factor |
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What are the most common sites of deposition of immune complexes systemic type III hypersensitivity?
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Kidney and joints
- high hemodynamic pressures associated w/ filtration function of glomerulus and synovium - in order for complexes to leave circ, need that high pressure as well as increased vascular permeability |
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What factors need to be present for systemic immune complex disease to be the most pathogenic?
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- antigen excess
- complexes are small or intermediate in size - complexes cleared less effectively by phagocytes and therefore circulate longer |
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What are the 2 types of T-cell mediated (Type IV) Hypersensitivity?
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1. delayed-type (DTH) --> Th1-type CD4+ T cells secrete cytokines --> recruitment of other cells (esp macrophages) that are major effectors of cell injury
2. direct cell cytotoxicity --> CD8+ T cells responsible for tissue damage |
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what may cause a false negative to a tuberculin test?
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immunosuppression or loss of CD4+ T cells (ex. HIV)
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granulomatous inflammation
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- special morphologic pattern of reaction resulting from prolonged DTH rxns against persistent microbes
- initial perivascular CD4 T infiltrate progressively replaced by macrophages over 2-3 weeks - accumulated macrophages exhibit morphologic evidence of activation --> flat, lg, eosinophilic (epitheloid cells) - aggregated macrophages w/ collar of lymphocytes |
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hyperacute rejection
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special form of rejection occurring in the setting where performed antidonor antibodies are present in circulation of host before transplant
- rejection w/in minutes to hours because circulating ab's bind to endothelium of grafted organ, w/ subsequent complement activation and vascular thrombosis - rarely occurs because potential recipients are screened for preformed anti-HLA ab's |
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Cyclosporine and FK506
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immunosuppressive drugs
- suppress T-cell mediated immunity by inhibiting transcription of cytokine genes, in particular the IL-2 gene |
