Inflammatory Mediators PDF

xtra note In ammatory mediators are like messengers in your body that deliver signals during the process of in ammation. When you get injured or have an infection, your body's defense system kicks in. In ammatory mediators are the substances that coordinate this response. They help bring immune cell...

xtra note In ammatory mediators are like messengers in your body that deliver signals during the process of in ammation. When you get injured or have an infection, your body's defense system kicks in. In ammatory mediators are the substances that coordinate this response. They help bring immune cells to the affected area, increase blood ow, and work together to heal the damage. She fifI m tmciEnesfns'eh 1k.mn a I iensgtigmation produce onlysynthesizedwhen • Involves venular contraction means the smallest veins have endothelial cells that will causes contraction responsible for permeability , and acute in ammatory cells can’t migrate from the vascular compartment to area of in ammation —> histamine will allow migration by fenetsration and cause sluggishness of blood stream ◦In the blood stream theres are cells that can’t attach to the walls of blood vessel and migrate unless the stream slows down ( slowing down comes from leakage of uid making the blood viscous and velocity decreases then there will be cells that will come close to the endothelial cells which attach then roll then reach fenestrations • Q. What cells are responsible for the release of histamine? Mast cells basophils and palatelets in reponse to injury liek trauma, cutting, in ammation they the E mainfunctionis withoutinjury • Mast cells have receptors called FcR receptor, when IgE attached to receptor there will be chemical reaction to secret teh prefomred granules release ng • Anaphylatoxins are part of the complementary system. ◦Compelemetary systems has 20 proteins and some proteins has sub proteins ◦C5a and C3a (after cleavage from c3 and c5) will cause anaphylotxin ◦Aaphylotoxin is reposnsible for teh release histamine • Cytokines release histamine of histamine ofserotonin source vascularinjury plateletaggregation ofthe P'getftp.dygfahuyme leafBerthon Yella's ofinflamma Proteffy plasmaderivedmediators factors coaguative startingwithfactor endingwithfibrinformation tmanfactor hag IL 1 IL 8 1. Clotting cascade • activation pf platlets to convert factor 12 into its active form 12a • Which converts brinogen into bren *is factor 1 • For point 3 it means: we have clotting system it is activated for blood clot formation if it doesnt stop our whole body will be clotted so they has to be breaks ◦Once clotting is done —> the brinolytic system will prevent clot formation startswith whentheseareasareexposed mum Formation exasperating thing fm kinin bradykinin Bradykhincauses functionofksystem Gwhatsthe that'swhywhen kininsystem isactivated by thifBronchospasm EXAM Q: What is teh function of kin in system? • its is vascular permeability because everything related to in ammation is related to vascular permeability • Arteriolar dialation • Non- vascular smooth muscle contraction because in blood vessels they have smooth muscles for contraction ( when kinin is active ther will be bronchoapasm • Kinin cascade starts by activation of klaikrein intermediate molecular that will stimulate the high moelculur kinin into bradykinin • Fibrolytic system comes from kalikrin activates plasminogen into plasmin and plasmin cause complement cascade • Plasmin will activate c3 into c3a causes anaphylotoxin which is responsible for the release 12 111 I2a Hla EX startsthe fiE ifii aaast.itis • Factor 12 activate the kinin system because of exposure of collagen and basement membrane ( since endothelial cells are damaged and basement membrane of it will be exposed ) ( factor 12 becomes active factor 12a) • Factor 12a will start clotting cascade, how? By activating factor 11(prothrombin) into factor 11a(thrombin) then thrombin activates brinogen into brin • Fibrin will make the rst hemosttaic mechanism by blood clot formation and forming mesh byactivating stimulates II fa.hr aifure active of inflammation 1a on I titiff causesanaphylotoxin whichisresponsible fortherelease of histamine Kinin system is related to clotting cascade Kinin cascade fibrinolyticsystem complement clotting cascade always start w Hageman factor factor 1 Exposure ofcollagen or basement 2 Xlla causes Xl Prothrombin 3 cascade 11 121 11 mem causes 119 Xla thrombin Xla converts soluble fibrinogen to insoluble fibrin fibrin is The first homeostatic mechanism bloodclot mesh forming by kinin cascade I Xlia Activation of Prekallikrein to Kakkinein By afanuses to bradykinin bradykinin HMWR Kallikrien stimulate 2 cascade Fibrinolytic 1 Kalliterien converts plasminogen plasmin activates to plasmin complimentarysystem plasmin activates to Ga releasing anaphylotoxin to release histamine • Complement is proteins from c1 to c9 in its inactive form • Alternative pathways starts from c3 not c1 nor c2 staysfrom 13 proteinsfrom t • The component system complementsystem ftp.ihfft wtf • In complement system theres a cellular phase of in ammation • Leukocyte chemotaxin means leukocytes can’t move to in ammation site so they follow a chemotaxin gradient to reach in ammation area increase in integrity activity ( cells attach in walls of endothelial cells when it migrates) • C3b when expressed it cause cell to macrophage ans idnetift the antigen and cause phagocytosis 0 not a creates the releaseof follow order reach by in the to chemotatic gradentto a inflammato caused.by I iagg causethecelltomacrophage Wife pL.IT af attractcel nkd.at's antigencbacteriavirus CAUSE PHAGOCYTOSIS • In complement system classical there will be c1qrs which stimulates C4 into c4 a and c4b and c2 into C2a and c2b • C3 • C4b and c2b is called c3 conevrtase so converters c3 into c3a ( anaphylatoxin and c3b is opsonin) • In classic pathway c3a will split c5 into c5a ( anaphylatoxin) and c5b, c5b will bind to c6 c7 c8 c9 creating a bullet to to penetrate teh membrane wall of bacteria this will also lead to lysis of teh cell • Teh membrane attack complex for nonnuclead cell one is enough for lyrsis of teh cell arecalled c convertase converts 3 to Csa tocab Ekchopnage i a in ie iii fi.ie beenough forthelysisofthecell nie neawa leadstothelysis the I 7 I Iggy • Platelets activating factor which is released from plaleters repsonsible for vascular permeability and leukocyte adhesion by moving through teh tsraem of blood and needs integrity to attach to the wall of endthelium • phospholipids in the cell membrane of platelets serve as a source of arachidonic acid, which is then converted into eicosanoids, including platelet-activating factors like prostaglandins and thromboxane A2. ARMIC a are math a fine leg • These are the main functions of the cytokines function b a which cell isthemajorplayerof acuteinflammation neutrophil macrophage in chronicinflam leukocyte • Q. Which cell is teh major cell of acute in ammation? Neutrophil, maceihoage • Q. Which cell is repsonsible for chronic in ammation? Leukocyte Q.pht • Which cells produces No? Macrophage during opozination release NO and endotehial cells • Nitric oxide decrease palatelts adhesion and aggregation and degranuualation dess e ÉÉ n in G Aredrivedfrom • When the cell is lysed theres lysosome Q. Which cells repsonsible for teh rlease of lysosomes? Neutrophils and macrophage after whenit'sdestroyed • Q. What is teh nature of lysosomal component? acid protease and neural protease • Neutral protease destroys the ECM of blood vessels, when ECM if blood vessels are destroyed it allows teh cells to transmit form vascular component into inter intertsial tissue itallowsthecelltotransmigratefromvascula Fa_cellularmatrixofthe Bu component interstitialtissue • Direct tissue injury rlease histamine histamine causes pain the is Tesponsible for membrang factorXII sopaincancomefrom p ressure swelling fluid nerve e nding histamine release the beof • Tissues injury —-> exposure of basement membrane of blood vessels activates classical pathway ——-> activation of factor 12 • Factor 12 a activates kinin system to activate bradykinin causing pain due to swelling putting pressure on nerve ending causing pain • bradykinin causes the release of arachiodonic acid ◦Archidonic acid has two pathways cyclogenase and leukoxygenase ◦Cycloxygenase rlease prostaglandin = pain ◦Leukoxygenase rlease leuoktrienes activate neutrophil and chemotaxin to site of in ammation causing phagocytosis and starts killing process. • How many sources of pain? Prostaglandin, bradykini, histamine ampene sRednes museeas His.tk gj.nep of due tothe fEtdgknkh.ca tt 1 mini causesreleaseofplasmaprote leaddtoedema causepain teddtoswelling refittin pintumperature Q whatare • Cells ar responsible for regeneration are still active sourceofexternal factorsaffecting thehealing process • These are clinical manifestation responsiblefor therelease of plasmamediato p sponsible for • Acute phase proteins are produced by hepatocytes • Hepatocytes are reposnsible for release of plasma mediator known are IL 6 responsible for acute phase proteins • Q. What is the response of teh release of IL6? vascular component • Hypotension causes fainting due to decrease volume of teh vessel be ofthe volume ofthevessel • Major cells in chronic in ammation is? • Neutrophils are multinucleated cells • Progressed to chronic in ammation and lead to: chronicinflammation Q.wggjmfntgte.tt c pinagnificism cells whatoccursduringchronic inf w fibrosis angiogenisis to attempt repair itprogressesinto hints ifeng.atffea fe i Macrophage G Who Are the 3plashmalceds 7 Eosinophils incy in lungs pleen tespan initiate by macrophage psonization process In liver intomacrophage Macrophages are ctaovated by T cell derived cytokines meaning they have work by message coming from T cells Also endotoxin form bacteria stimulate macrophages by opsinization process We have different name sof macrophage depending on its location B lymophtes come from? Neon marrow and antibodies are produced by plasma cells Macrophages engulfs the antigen ( like bacteria) rlease of cytokines stimulate helper T cells whihc will be matured into a memory cells so when the infection comes again it can recognize it Helper T cells stimulate IL2 to stimulate other cytosine T cells couldbebacteria foreignbody endotoxin release when it of comesagain itcanrecognize Ea I Helper T cells stimulates b celll and cytotoxic T cells and memory helper T cell Q. What type of in ammation do we have in chronic in ammation? epilhelioid cell granuloma macrophages Thatto epithelial cell morphology becomes G 2 hastheability multinucleated tounitewith giant cells oneanother will be responsible tuberculosis forkilling H caps silica suturematerial In grnaulomatus in ammation there will be a lot of T cells and theres macrophages Macrophages were present and change its morphology to epitheliodl Cells which make iit hav tehe baility to unite with one another so they’re will be mulitnuelted hgiant cell an depitheloid cell Giant cells are responsible for killing TB , hsitomplasmic capsule, silica 9ar 3ndna tissue demage, this should be removed what system is reposnsible for removal of toxic material responsible fortheremoval of thetoxicmaterialsfrom thebody Produces antigen, to form more t lymphocytes Information of lymphatic system Because of tenderness or pain In heart the brous in ammation works like a cheese between 2 breads theres stickiness Fetsponsibutorpusformation Fever comes form IL6 and TNF and IL1 Fever is the main systemic cause of in ammation with fever theres is: Come from IL6 g