Efficient Consumer Response Respuesta Eficiente al Consumidor.
Innate Response - 1A
Transcript of Innate Response - 1A
Universidad*Interamericana*de*Puerto*Rico*Recinto*Metropolitano*
Facultad*de*Ciencias*y*Tecnología*Escuela*de*Tecnología*Médica!
Inmunología*Clínica!
Dr.!Rafael!Tosado!Acevedo!
History(of(Immunology(
• 1798(4(Edward(Jenner:(the(father(of(Immunology(• 1840(4(Jacob(Henle:(propose(germ(theory(• 1862(4(Ernst(Haeckel:(phagocytosis(
• 1880(4(Louis(Pasteur:(live(aMenuated(microorganisms(for(vaccinaNon(
• 1895(4(Jules(Bordet:(serum(complement(acNvity(• 1900(4(Paul(Ehrlich:(anNbodies(
• 20(novel(prizes(in(Immunology(so(far(
Sara(Nelmes(
Edward(Jenner(James(Phillips(
Inmunidad:*la?n!immunitas!!(liberarse*de)!
Respuesta*Inmune*en*mamíferos:!• Respuesta!Innata!
– Conjunto!de!defensas!con!las!que!nacemos.!
• Respuesta!Adquirida!– Se!produce!una!vez!que!entramos!en!contacto!con!un!anWgeno.!
• AnWgeno!(Ag)!o!Inmunógeno!– Agente!que!induce!una!respuesta!inmune!!
• Exógeno!o!propio!• Alergeno!
• AnNcuerpo!(Ab)!– Inmunoglobulinas!(proteínas)!solubles!que!reconocen!y!se!unen!a!Ags!específicos!– Producidos!por!linfocitos!B!
Figure(1423(
Figure!1M32!
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First!Line!of!Defense:!Physical!Barriers!
• Prevent!entrance!of!microorganism!unless!the!find!a!entry!portal.!
Inmunidad*Innata*
• Barreras!Físicas!• Mucosas!!– mucosidad!atrapa!microorganismos!y!parWculas!inmunogénmicas!
– impide!adherencia!de!microorganismos!
– Se!remueven!!por!la!acción!ciliar.!!!
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Piel se irigima del ectodrmo‣Del endodermo - sist. digestivo, pulmonr. Urogenital, etc, etc‣
Inmunidad*Innata*Barreras!Físicas!!
– Epitelio!Respiratorio!• Cilios,!Tos!y!estornudos.!
– Lágrimas!• Lysozima!
– Saliva!• Lysozima,!agentes!anNvirales!
– Orina.!• pH!y!flujo!líquido!
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Inmunidad*Innata*
Barreras!Físicas!
• Tracto!gastrointesNnal!
– HCl,!sales!biliares!– pepNdasas!– Movimientos!peristálNcos!
• Semen!
– espermina!y!zinc!
• Tracto!vaginal!
– pH,!flora!residente!!
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Inmunidad(Innata(
Barreras(Físicas(
• lactoperoxidasa((– en(leche(
• Lisozima(
– lágrimas,(saliva(y(secreciones(nasales(
• Microflora(normal(– bacterias(y(hongos((lactobacilus)(– Bactericinas((colicinas)(
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Microflora(Normal(
• Bacterias(– E.coli,(Lactobacillus(– Producción(de(Bactericinas((colicinas)(
• Levaduras(– Candida(albicans(
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Células(Tallo(del(Sistema(Inmune(
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>>>Stem cells vs. celulas madres = en ingles no hay celulas madres
embrionic stem cells - celukas madres (se puede convertir en cualkier tipo de celula) totipotentes stem cells - celulas delcordon umbilicar, celula de ;a medula osea (han sudrido ungrado de diferenciacion y no se pueden converir en cualkier tipo e celula)
• Cells!of!the!myeloid!lineage!perform!various!important!funcNons!in!the!immune!response.!In!the!rest!of!the!book,!these!cells!will!be!represented!in!the!schemaNc!form!shown!on!the!lef.!!
• Macrophages!and!neutrophils!are!primarily!phagocyNc!cells!that!engulf!pathogens!and!destroy!them!in!intracellular!vesicles,!a!funcNon!they!perform!in!both!innate!and!adapNve!immune!responses.!!
• DendriNc(cells(are(phagocyNc(when(they(are(immature(and(can(take(up(pathogens;(afer(maturing,(they(funcNon(as(specialized(cells(that(present(pathogen(anNgens(to(T(lymphocytes(in(a(form(they(can(recognize,(thus(acNvaNng(T(lymphocytes(and(iniNaNng(adapNve(immune(responses.((
• Macrophages(can(also(present(anNgens(to(T(lymphocytes(and(can(acNvate(them.(The(other(myeloid(cells(are(primarily(secretory(cells(that(release(the(contents(of(their(prominent(granules(upon(acNvaNon(via(anNbody(during(an(adapNve(immune(response.((
• Eosinophils!are!thought!to!be!involved!in!aMacking!large!anNbodyMcoated!parasites!such!as!worms;!basophils!are!also!thought!to!be!involved!in!anNparasite!immunity.!!
• Mast!cells!are!Nssue!cells!that!trigger!a!local!inflammatory!response!to!anNgen!by!releasing!substances!that!act!on!local!blood!vessels.!!
• Mast!cells,!eosinophils,!and!basophils!are!also!important!in!allergic!responses.!!
DendriNc(cells(form(a(key(link(between(the(innate(immune(system(and(the(adapNve(immune(system.(
• Like!the!other!cells!of!innate!immunity,!dendriNc!cells!recognize!pathogens!via!invariant!cellMsurface!receptors!for!pathogen!molecules,!and!are!acNvated!by!these!sNmuli!early!in!an!infecNon.!!
• DendriNc!cells!in!the!Nssues!are!phagocyNc!and!are!specialized!to!ingest!a!wide!range!of!pathogens!and!to!display!their!anNgens!at!the!dendriNc!cell!surface!in!a!form!that!can!be!recognized!by!T!cells.!
• AcNvated!dendriNc!cells!also!produce!molecules!that!enable!T!cells!to!be!acNvated!by!anNgen.!
1-4 The lymphoid lineage comprises the lymphocytes of the adaptive immune system and the natural killer cells of innate immunity
Natural(killer((NK)(cells.(
• These(are(large(granular(lymphoid4like(cells(with(important(funcNons(in(innate(immunity,(especially(against(intracellular(infecNons,(being(able(to(kill(other(cells.(Unlike(lymphocytes,(they(lack(anNgen4specific(receptors.(
Tincion!de!Wright/Giemsa!
!!!!!!!!!!!!!!Fijador!!!!!eosina!!!!!!!azul!de!meNleno!
WBC(–(IdenNfique(((
A. Monocito. B. neutrofilo. C. Linfocito. D. Plaquetas. E. neutrofilo. F. EosinofiloG. Basofilo
Eritrocitos son los mas abundantes. 4.5(4.7) -6 xEE6 (hombre) Mujer __________????‣
The(Second(Line(of(Defense:(Innate(Cellular(Response(
• Cellular(Response((The(BaMle(Front)(– First(reponders(in(Nssues(are(Macrophages(and(Mast(cells.(
– Citokines(produced(by(these(cells(recruit(Polymofonuclear((PMNs)(leucocytes(to(the(point(of(infecNon.(
Plaquetas 150000-400000. <40000 emergencia‣
Si el miroorganismo logra pasar lam primera linea d defensa (barrera fisica d la piel y mucosa), ataques quimicos y a los ‣medanismos mecanicos, se encuentran cn edas celulas. Las dendriticas son las q llevan y traen, no atacan.v‣
INFLAMATION*
IniJal*Cellular*Responders*to*Invasion*
First*Responders:**Macrophages***&***Mast*Cells*
Inflamacion es la resouesta mas importante Iniciads x los macrofagos y los mast cells
Los mast cells son. Las q suean la alarma de q ya pasaron la primera linea ◦
Alarma - citoquinas ‣Y se encienden la resouesta inflamatoria•
ProtecJve(Host(Response(to(Injury(
• Edema(dilutes(toxins(
• Phagocytosis(remove(bacteria(and(cell(debris(
• IniJate(healing(and(repair(
• Wall(off((infecJon(
Kinins*
• SJmulate*vasodilaJon,*increased*vascular*permeability*and*pain.*
• *AcJvated*by*products*of*the*intrinsic**coagulaJon*system*
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Turgor- hinchazon o edema, hinchazon es xq sale el plasma◦
Hinchazon para diluir, sirvend senal para neurtrofilod y macrofagos‣Rubor◦
Calor◦
Dolor◦
Complement(
• Complement(proteins(can(be(acJvated(via(– anJgenGanJbody(reacJons((classical(pathway)(– bacterial(products((alternate(pathway(or(MBGlecJn)(
• AcJvaJon(occurs(on(cell(surface(and(serves(to(increase(blood(flow(and(aXract(PMNs(
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COMPLEMENT*ACTIVATION*
Complement(
Complement(is(a(series(of(serum(proteins(
• Classical(pathway(– acJvated(via(anJbodies(
• Alternate(pathway((– AcJvated(by(bacterial(products(
• AcJvaJon(occurs(on(cell(surface(and(serves(to(increase(blood(flow(and(aXract(PMNs.(
AcJons*of*Complement*
– *Chemotaxis*
– *OpsonizaJon*
– *Increased*vascular*permeability*
– *InteracJon*with*coagulaJon*
– *Cell*lysis*
Blood(Clo[ng(
• 1.(InflammaJon(results(in(acJvaJon(of(the(coagulaJon(system(
• 2.(Components(of(the(coagulaJon(system(serve(as(inflammatory(mediators(
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*Platelets*
Megakaryocyte(FragmentaNon(
Otras*moléculas*envueltas*en*Inflamación!
• LISOZIMA!(muraminidasa)!!– rompe!la!pared!bacteriana.!
• PROTEÍNAS!DE!LA!FASE!AGUDA!!– aumentan!en!respuesta!a!la!liberación!de!mediadores!
• ILM1!e!ILM6.!• Pentraxina!M!Proteína!C!ReacNva!(CRP)!
– AcNva!Complemento.!
• Amiloide!Sérico!P!(SAP)!Pentámero!de!la!familia!de!la!CRP.!
• Proteína!que!une!Manosa!(MBP)!M!ColecNnas!– MúlNples!Complejos!Triméricos.!
• Fibrinógeno!– α1M!anNtripsina!
• Factores!del!Complemento!– C3,!C9,!Factor!B!
• Interferones!61!RTA!
Acute(Phase(Proteins(
• Synthesized(by(the(liver:(promote(and(control(inflammatory(response(
• Include(C(reacJve(Protein,(alphaG1(anJtrypsin,(ceruloplasmin,(haptoglobin,(and(fibrinogen(
• Lead(to(increased(erythrocyte(sedimentaJon(rate((ESR)(
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Serum*Proteins*PAGE*
Inflammatory(cytokines(
Monocito y neutrofilo
The!Third!Line!of!Defense:!AdapNve!Immune!Response!
• Humoral!immunity,!the!Intelligence!– Humoral!immunity!is!due!to!the!acNvity!of!lymphocytes.!
– Some!lymphocytes!produce!anNbodies!(Abs)!that!provide!long!lasNng!immunity.!
Linfocito no hay forma d decir si es T o BHay q marcar cn florecencia para poder saber cual es
Lymphocytes!are!mostly!small!and!inacNve!cells!
• The!upper!panel!shows!a!light!micrograph!of!a!small!lymphocyte!in!which!the!nucleus!has!been!stained!purple!by!the!hematoxylin!and!eosin!dye,!surrounded!by!red!blood!cells!(which!have!no!nuclei).!!
• The!darker!purple!patches!of!condensed!chromaNn!of!the!lymphocyte!nucleus,!indicaNng!liMle!transcripNonal!acNvity,!the!relaNve!absence!of!cytoplasm,!and!the!small!size.!!
• Evidence!of!funcNonal!inacNvity:!the!condensed!chromaNn,!the!scanty!cytoplasm,!and!the!absence!of!rough!endoplasmic!reNculum.!Photographs!courtesy!of!N.!Rooney.!
Linfosito q no se puede todavia decir si es B o T
1-5 Lymphocytes mature in the bone marrow or the thymus and then congregate in lymphoid tissues throughout the body
Componentes*de*la*Respuesta*Inmune!Respuesta*Innata*
*(No*Específica)!
• Celular!– Fagocitos!(PMN,!monocitos)!– Células!citotóxicas!(linfocitos!
NK)!– Células!Inflamatorias!
(mastocitos,!trombocitos)!
• Factores!Solubles!– Complemento!– Citoquinas!– Interleuquinas!– Interferones!– Enzimas!hidrolílicas!
Respuesta*Adquirida*
*(Específica)!
• Celular!
– Linfocitos!B!– Linfocitos!T!– AbMDependent!Cell!Citotoxicity!
(ADCC)!
• Factores!solubles!(Respuesta!Humoral)!– AnNcuerpos!– Linfoquinas!– Complemento!
• Vía!clásica!
Menos especifica