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  Inflammatory response: 1. Vascular reaction2. Cellular reaction Circulating cells: 1. Neutrophils2. Monocytes3. Eosinophils4. Lymphocytes5. Basophils6. Platelets Tissue cells: 1. Mast cells2. Bloo !essels3. i#ro#lasts4. $esient M%5. $esient lymphocytes Extracellular matrix: 1. &tructural 'i#rous proteins ( colla)en ( elastin2. *hesi!e )lycoproteins ( 'i#ronectin ( laminin ( non'i#rillar colla)en ( tenascin3. Proteo)lycans i)ure 2(1  i)ure 2(2 i)ure 2(3 Acute Inflammation: 1. *lterations in !ascular cali#er   increase in #loo 'lo+2. &tructural chan)es in the micro!ascular   increase permea#ility3. Emi)ration o' leu,ocytes   accumulation at site o' in-ury   acti!ation HALLMARK  o' acute in'lammation / increase !ascular permea#ility Stimuli for Acute Inflammation: 1. 0n'ections2. rauma3. Physical an chemical a)ents4. issue necrosis5. orei)n #oies6. 0mmune reactions Changes in ascular !lo an# Cali$er: 1. ransient !asoconstriction2. Vasoilation 'irst at the arterioles histamine N3. 0ncrease !ascular permea#ility   protein into etra!ascular space4. 0ncrease !iscosity o' #loo   #loo stasis5. Leu,ocytes mo!e to enothelial +all   roll   ahere   mi)rate  i)ure 2(5 Mechanisms of Increase# ascular %ermea$ility: 1. ormation o' enothelial )aps in !enules ( !enules ( rapi an short li!e 15(37 min ( most common mechanism8 9immeiate transient response: ( histamine #ray,inin Ls su#stance P   #in to their receptors   intracellular  si)nalin) path+ays   contraction o' cytos,eletal proteins myosin   contraction o' enothelial cells   separation o' intercellular -unctions ( 0L(1 N  0 N(;8 elaye an lon) li!e 4(6 hrs8 lastin) 24 hrs or more2. <irect enothelial in-ury ( !enules capillaries arterioles ( results in enothelial cell necrosis an etachment ( immeiate sustaine response ( may result in platelet cell ahesion an throm#osis3. <elaye prolon)e lea,a)e ( !enules an capillaries ( #e)ins a'ter a elay o' 2(12 hrs8 lasts 'or hrs to ays ( sun#urns (raiation =V raiation4. Leu,ocyte(meiate enothelial in-ury ( !enules an pulmonary an )lomerular capillaries ( leu,ocytes that ahere to the enothelium may #ecome acti!ate   release toic oy)en species an proteolytic en>ymes   enothelial in-ury or etachment   increase permea#ility5. 0ncrease transcytosis ( channels consistin) o' clusters o' interconnecte uncoate !esicles an !acuoles8 calle the 9!esiculo!acuolar or)anelle: ( VE? increases the num#er an si>e o' these6. Lea,a)e 'rom ne+ #loo !essels ( an)io)enesis8 ne+ !essel sprouts remain lea,y until the enothelial cells mature ( VE? inuces an)io)enesis an increases !ascular permea#ility  Bloo stasis   leu,ocytes mar)inate   leu,ocytes roll   #ecome acti!ate   ahere to the enothelium   transmi)rate across the enothelium !enules   pierce the BM   mi)rate to+ar chemoattractants to the source o' in-ury A#hesion receptors in&ol&e#: 1. &electins ( E(selectin / on enothel ( P(selectin / on enothel @ plts ( L(selectin / on leu,ocytes2. 0mmuno)lo#in 'amily ( 0C*M(1 ( VC*M(1 ( PEC*M C<313. 0nte)rins ( L *(1 ( Mac(1 C$3 ( p157A5 C$44. Mucin(li,e )lycoproteins ( heparin sul'ate ( P&?L(1 ( ?lyC*M(1 ( E&L(1 ( C<34 Rolling  ahesion to actii!. enothelium neutrophils monocytes  cells0mportant in homin) o' e''ector @ memory  cells8 esp. to s,in&ialyl(Le+is( &ialyl(Le+is *E(selectin enothelium Transmigration 8 Leu,ocyte mi)ration throu)h enotheliumC<31C<31 PEC*MLymphocyte homin) to hi)h enothelial !enules EV *lso ser!es to #in neutrophils to acti!ate enotheliumL(selectin?lyC*M(18 MaC*M(18 C<34 A#hesion  eosinophils monocytes lymphocytesVL*4 !ery late acti!ation / meiates homin) o' lymphocytes to enothel at peripheral sites o' in'lammationD 1(inte)rins 1 VL*4 F4D1 2 LP*M(1 F4DGVC*M(1!ascular cell ahesion molecule(1 A#hesion  arrest transmi)ration all leu,ocytesL *(1 / meiates leu,ocyte ahesion to *PC an !asc. enotheliumMac(1 C$3 / meiates leu,ocyte attachment to enothel8 'unc as 'i#rino)en receptor8 'unc as CH receptor on pha)ocytic cells #ins iC3# on opsoni>e iC3# coate cellsp157A5 C$4 / meiates leu,ocyte attachment to enotheliumD 2(inte)rins 1 L *(1 C<11aIC<1J 2 Mac(1 C$3 C<11#IC<1J 3 P157A5 C$4 C<11cIC<1J0C*M(1 intercellular ahesion molecule (1 Rolling  neutrophils monocytes lymphocytes8 selectins #in to sialylate(Le+is( +hich themsel!es are co!alently #oun to !arious mucin(li,e )p ?lyC*M(1 P&?L(1 E&L(1 C<34&ialyl(Le+is(8 P&?L(1 P(selectin )lycoprotein li)an(1P(selectin enothel @ plt Ma'or RoleLeu(ocyte Receptor En#othelial Molecule Ta$le )*+ En#othelial,Leu(ocyte A#hesion Molecules 0nuce enothelial epression o' 1 VC*M(1 2 0C*M(1 3 E(selectin / epression o' E(selectin / HALLMARK  o' acute cyto,ine meiate in'lammationistamine throm#in P* / cause release o' P(selectin 'rom Kei#el(Palae #oy to enothel sur'ace*cti! neutrophils to increase a!iity o' inte)rinsB1 inte)rin an C<44 / #in matri proteinsChemotais1 eo)enous / #acterial LP&2 eno)enous / C5a LB4 0L(Jheparan sul'ate ?*?s
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