1-29-10 Allergy and Hypersensitivity 1.

Define: Inflammation: a highly regulated physiologic response to perceived injury (physical, chemical, biological) characteri ed by! "ellular changes! vascular dilation and lea#age, leu#ocyte in$iltration, local hypo%ic environment, secondary tissue damage &iochem changes! in$lammatory mediator release'activation'synthesis including histamine, cyto#ines, arachadonic acid derivatives( activation o$ complement, #inins, and coagulation "linically mani$ess as the ) cardinal signs (rubor, tumor, calor, dolor, $unctio laesa Hypersensitivity: heightened host responsiveness to normally innocuous substances Allergy: immune-mediated hypersensitivity( *g+ mediated vs other mechanisms Atopy: genetic predisposition to *g+ mediated responses 2. Describe the pathophyisologic mechanisms of Types I, II, III, and IV hypersensitivity. Type I *mmediate Hypersensitivity! plasma cells secrete *g+ upon re-e%posure to an allergen, ,hich bind -c./1 receptors on mast cells0 1he mast cells degranulate releaseing histamine, leu#otrienes, and prostaglandins0 1hese compounds produce an immediate hypersensitivity reaction0 "yto#ines are also released, and these produce a late phase reaction 2-23 hours a$ter ree%posure0 Type II Antibody-mediated 4iseases! & cells recogni e $oreign antigens and release large amounts o$ *g5 and *g6, ,hich opsini e cells $or complement activation and phagocytosis0 Type III *mmune comple%-mediate 4iseases! triggered by circulating antigens that are not membrane bound0 *g5 and *g6 bind to these antigens and $orm immune comple%es that macrophages can phagocytose0 7maller immune comple%es may escape phagocytosis and deposit in small vessels, joints, and glomeruli0 Type IV 4elayed 1ype 1-cell mediated 4iseases! as name suggests, this ta#es 2-8 days to develop0 5acrophages present antigen via 5H" molecules to helper and cytoto%ic 1 cells, and secrete *9-12 to $urther activate them0 1hey cytoto%ic cells go on to destroy the in$ected cells, ,hile helper 1 cells secrete *-:-gamma and *9-2 to $urther activate macrophages0 . Describe the cell!lar mechanisms of Ig"#mediated hypersensitivity. 7ee the description $or 1ype * hypersensitivity0 *n greater detail!

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antigen-speci$ic *g5; & cells are induced to s,itch to *g+ production a$ter being e%posed to antigen and cyto#ines *g+ antibody is secreted0 1he *g+ binds to -c./1 receptors on mast cells and basophils0 7ubse<uent antigen e%posure bridges *g+ molecules occupying -c./1 receptors -c./1 bridging initiates the signal to generate and release in$lammatory mediators, ,hich initiate tissue damage a0 Acute phase (driven by vasoactive amines and peptides) sets on 10-20 minutes b0 9ate phase (driven by cyto#ines) sets on in 3-= hours0

>ltimately, 1ype * *g+-mediated hypersensitivity a$$ects 20? o$ the total population, causing asthma, allergic rhinitis, ec ema, urticaria, anaphyla%is, ,hee ing, snee ing and death $. Describe the differences bet%een mast cells and basophils. &ast cells! mononuclear, located in tissues, metachromic granules, in$lammatory mediators, -c./1 receptors 'asophils! polymorphonuclear, located in circulation, metachromic granules, in$lammatory mediators, -c./1 receptors (. )!tline the mast cell#associated mediators of inflammation. Histamine, serotonin, heparin, prostaglandin 42, leu#otriene "3, platelet activating $actor, and eosinophile chemotactic $actor (cyto#ine)0 *. Describe the eosinophil involvement in inflammatory in+!ry. +osinophils are #no,n $or their role in $ighting helminth in$ections (via A4"") and $ighting viral in$ections0 *t is also implicated in allergic responses and asthma pathogenesis, and can cause tissue damage0 +osinophil granules contain major basic protein as the core, and eosinophil cationic protein and neuroto%in in the matri%0 ,. Define: Immediate hypersensitivity s-in test: an in vivo test $or Ag-speci$ic *g+0 @lace the allergen directly in contact ,ith the s#in0 5ultiple samples o$ allergens are o$ten tested at once, leaving a patient ,ith a plethora o$ immediate locali ed 1ype 1 reactions0 .adioallergosorbent test /.A0T1: an in vitro test $or Ag-speci$ic *g+0 Allergen is bound to an insoluble sur$ace, and patient serum is added0 /adiolabeled anti-*g+ is then added to see i$ there ,as any allergen-speci$ic *g+ in the serum0