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!

8(RTA(

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.!!!

11!RTA!

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!

13!RTA!

Inmunidad*Innata*

Barreras!Físicas!

•  Tracto!gastrointesNnal!

–  HCl,!sales!biliares!–  pepNdasas!–  Movimientos!peristálNcos!

•  Semen!

–  espermina!y!zinc!

•  Tracto!vaginal!

–  pH,!flora!residente!!

15!RTA!

Inmunidad(Innata(

Barreras(Físicas(

•  lactoperoxidasa((– en(leche(

•  Lisozima(

–  lágrimas,(saliva(y(secreciones(nasales(

•  Microflora(normal(– bacterias(y(hongos((lactobacilus)(– Bactericinas((colicinas)(

16(RTA(

Microflora(Normal(

•  Bacterias(–  E.coli,(Lactobacillus(–  Producción(de(Bactericinas((colicinas)(

•  Levaduras(–  Candida(albicans(

28(RTA(

Células(Tallo(del(Sistema(Inmune(

30(RTA(

>>>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*

53!RTA!

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(

54(RTA(

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(

58(RTA(

*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)(

62(RTA(

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