Figure'1)7'

Major&Lymphoid&Organs&

•  Thymus&–  Located(in(the(front(of(the(upper(chest(–  Nursery(for(the(development(of(T(cells.(

•  Spleen(–  Located(in(the(upper(le=(side(of(your(abdomen(–  Filters(out(foreign(organisms(from(blood(–  Removing(old(or(damaged(platelets(and(red(blood(cells(–  Stores(extra(blood(and(releases(it(as(needed(–  Developmenof(white(blood(cells(–  Removal(may(lower(resistance(to(infecDon.(

•  Bone&marrow(–  Located(in(the(middle(of(bones,(specifically(vertebrae,(pelvic,(and(leg(

bones(–  Generates(T(cells,(B(cells,(and(macrophages(

No es parte d los major lymphoid organs

•  Lymph&nodes&

–  Hundreds'of'lymph'nodes'are'located'throughout'your'body'–  Filter'lymph'fluid'–  Remove'anDgens,'bacteria,'and'cancer'cells'–  Weblike'structure'traps'foreing'agents'allowing'macrophages,'

anDbodies,'and'T'cells'to'destroy'them.''–  Removal'any'lymph'nodes'during'breast'cancer'surgery'does'not'

compromise'your'overall'lymph'node'protecDon.''

Minor&Lymphoid&Organs&

Figure'1)11'

Copyright(©(The(McGrawIHill(Companies,(Inc.((

B&and&T&cell&Developpment&

CirculaDng(lymphocytes(encounter(anDgen(in(peripheral(lymphoid(organs.(

•  Naive(lymphocytes(recirculate(constantly(through(peripheral(lymphoid(Dssue,(here(illustrated(as(a(popliteal(lymph(node—a(lymph(node(situated(behind(the(knee.((

–  In(the(case(of(an(infecDon(in(the(foot,(this(will(be(the(draining(lymph(node,(where(lymphocytes(may(encounter(their(specific(anDgens(and(become(acDvated.(

•  Both(acDvated(and(nonacDvated(lymphocytes(are(returned(to(the(bloodstream(via(the(lymphaDc(system.(

OrganizaDon'of'a'lymph'node.'

•  As'shown'in'the'diagram'on'the'le=,'which'shows'a'lymph'node'in'longitudinal'secDon,'a'lymph'node'consists'of'an'outermost'cortex'and'an'inner'medulla.'The'cortex'is'composed'of'an'outer'cortex'of'B'cells'organized'into'lymphoid'follicles,'and'deep,'or'paracorDcal,'areas'made'up'mainly'of'T'cells'and'dendriDc'cells.''

•  When'an'immune'response'is'under'way,'some'of'the'follicles'contain'central'areas'of'intense'B)cell'proliferaDon'called'germinal'centers'and'are'known'as'secondary'lymphoid'follicles.'These'reacDons'are'very'dramaDc,'but'eventually'die'out'as'senescent'germinal'centers.''

•  Lymph'draining'from'the'extracellular'spaces'of'the'body'carries'anDgens'in'phagocyDc'dendriDc'cells'and'phagocyDc'macrophages'from'the'Dssues'to'the'lymph'node'via'the'afferent'lymphaDcs.'These'migrate'directly'from'the'sinuses'into'the'cellular'parts'of'the'node.'Lymph'leaves'by'the'efferent'lymphaDcs'in'the'medulla.'The'medulla'consists'of'strings'of'macrophages'and'anDbody)secreDng'plasma'cells'known'as'the'medullary'cords.''

•  Naive'lymphocytes'enter'the'node'from'the'bloodstream'through'specialized'postcapillary'venules'(not'shown)'and'leave'with'the'lymph'through'the'efferent'lymphaDc.'The'light'micrograph'shows'a'transverse'secDon'through'a'lymph'node,'with'prominent'follicles'containing'germinal'centers.'

Mucosal Associated Lymphoid Tissues (MALT)

86'RTA'

87(RTA(

88'RTA'

Macrophage(phagocytosing(Streptococcus*pyogenes((

90'RTA'

91(

MONOCYTE7MACROPHAGES&

Types&–  &&&&&&&&Macrophages&7&in&connecGve&Gssues&–  &&&&&&&&Alveolar&macrophages&7&in&lung&

–  &&&&&&&&Kupffer&cells&7&liver&–  &&&&&&&&Langerhans&cells&7&epidermis&

–  &&&&&&&&DendriGc&–travel&from&Gssues&to&lymph&nodes&–  &&&&&&&&Microglia&7&brain&

92'RTA'

Macrophages(are(phagocytes(

•  Recognize(pathogens(via(surface(receptors(– Mannose(and(scavenger(receptors(

–  TollIlike(Receptors((TLRI2,(TLRI4)(–  CD14(

•  Destroy(pathogens(in(phagosomes(

– May(be(able(to(stop(invasion(at(this(stage(

•  Secrete(numerous(cytokines(

93(RTA(

Macrophage&cytokine&funcGons&

•  AcDvate'natural'killer'cells'

•  Induce'the'inflammatory'vascular'response'

•  Induce'the'inflammatory'cellular'response'

Empece a grabar 1:34

Chemotaxis

Mast Cell

Mast Cell

PMN

Eosinophil

95(RTA(

Chemotaxis'

Release&of&macrophage&chemotacGc&factor&

Figure'1)12'Extrabasacion‣

PMN&ROLLING,&STOPPING,&AGGREGATING,&AND&MIGRATING&

ROLLING STOPPING AGGREGATION & SHAPE CHANGE

TRANSENDOTHELIAL MIGRATION

L-SELECTIN P-SELECTIN E-SELECTIN

INTEGRINS ICAMS VCAMS

CD11/CD18 P-SELECTIN

INTEGRINS ICAM VCAM PCAM

99(RTA(

SEROUS&AND&&FIBRINOUS&&EXUDATES&

Interferones&(IFN)&

•  Propiedades(anDvirales(– Modulan(la(acDvidad(de(las(células(NK(y(

macrófagos(

•  Interferones(α,(β(y(γ(– se(encuentran(en(muchas(especies(

– producidas(por(muchas(células(

•  fibroblastos,(leucocitos(•  célula(infectada(con(un(virus(

101(RTA(

Interferones&(IFN)&

Protege'células'no'infectadas'por'virus'

•  produce'derrepresión'de'dos'genes'–  proteína'quinasa'bloquea'la'transcripción'de'mRNA'

•  gene'que'cataliza'la'formación'de'un'polímero'pequeño'

–  acDva'una'endonucleasa''–  degrada'el'mRNA'viral'y'del'huésped''

•  Produce'un'círculo'de'células'sanas'

102'RTA'

MAST(CELLS(

103(RTA(

MAST CELL Chemicals

Mechanical Injury

IgE + Allergen

Activated Complement

Mast Cell Degranulation

104'RTA'

Dentro de los granos hay acido araquidonico.•

Arachidonic&acid&metabolites&a.   Prostaglandins&

&&&L&vasodilaGon,&vascular&permeability,&pain&

b.   Thomboxane&A2&(from&platelets)&&&L&&vasoconstricGon,&bronchoconstricGon,&and&platelet&

aggregaGon&

c.   Leukotrienes&(from&mast&cells&and&WBC)&&L&LTC4,D4,E4&=&SRSA&(Slow&reacGng&substance&of&anaphylaxis)&&L&LTB4&=&ECFA&(chemotacGc&for&eosinophils&and&neutrophils)&

d.   Platelet&acGvaGng&factor&105(RTA(

Parte d las histaminas, leucotrienos,etc......van a nurstros tejidos y x eso gotea la nariz, etc•Benadryl- bloquea los receptores d la histamina (1rst genration)•De 2nd generacion (allegra, etc) bloquea la histamina•

106'RTA'

ARACHIDONATE&METABOLISM&ARACHIDONATE

PROSTAGLANDIN PRECURSOR

PROSTAGLANDINS EX. PGI2 AND PGE THROMBOXANES

LEUKOTRIENE PRECURSOR

LTB4

LTC4 LTD4 LTE4

OXYGEN RADICALS

PLATELET ACTIVATING

FACTOR COX 1 &2 LIPOXYGENASE

107(RTA(

Todas son bn inflamatorias (los ultimos de cada columna)‣

Leucotrienos bn importantes en el asma•Cingulair bloquea leucotrienos◦

BASOPHILS&

a.   PhagocyGc&

b.   Release&histamine,&leukotrienes,&prostaglandins&

108'RTA'

EOSINOPHILS&

a.   Release&numerous&inflammatory&cytokines&that&can&result&in&prolonged&or&recurrent&inflammaGon&and&Gssue&damage&

b.   Produce&basic&caGonic&protein&which&kills&parasites,&also&produces&chemotacGc&factors&to&parasites&

c.   Are&a&key&part&of&anaphylaxis&and&allergy&response&109(RTA(

INFLAMMATORY&CELLS&IN&TISSUES&

110'RTA'

*****empece otra vez amgrabar 1:50

POLYMORPHONUCLEAR&NEUTROPHIL&

111(RTA(

Pare a las 1:55 y emepce 1:57

PMNs&a\racted&to&wound&area&by&chemotacGc&factors&of&the&immune&response&or&by&products&of&

bacterial&infecGon.&112'RTA'

Animacion leucotrinos extravasation (kuby inmunology)•

pare 1:59Comenzo 2:08

Phagocytosis

C3b

Antibody

EncapsulatedBacteria

Lysozyme and elastase

Cationic Proteins

Lactoferrin

Lactic Acid and Toxic Oxygen Radicals

113(RTA(

Fagositosis ayudada x la opsonizacion‣

Quimiotáxis'y'Fagocitósis'Video (garland science)‣

Neutrophil&phagocytosis&&occurs&by&extension&of&&pseudopods&toward&&bacteria&and&debris&&with&engulfment&and&&

digesGon&through&release&&of&hydrolyGc&enzymes&&and&oxygen&radicals.&

115(RTA(

OpsonizaDon'

Video‣

Phagocytosis&is&facilitated&by&opsonizaGon&

CoaGng&of&the&bacteria&with&anGbody&and&complement&C3b.&&

Neutrophils&bind&with&C3b&and&anGbody&at&Fc&receptor.&&

FibronecGn&and&CLreacGve&protein&can&opsonize&bacteria&

117(RTA(

118'RTA'

Fagocitosis&y&Muerte&Intracelular(

119(RTA(

Mecanismo&de&Muerte&Dependientes&de&O2&•  Formación'de'Intermediarios'ReacDvos'de'Oxígeno'(ROI)'

–  a'parDr'del'NADPH'

–  Vía'del'Monofosfato'de'Hexosa'(presencia'de'una'oxidasa)'•  NADPH'+'O2''NADP+'+'•'O2

)''

' ' 'Aniones'de'superóxido'(•O2))''

' ' ' '' ' ''''''dismutasa'de'H2O2'

' ' 'estables'H2O2'

' ' ' '' ' 'Fe2+''

' ' 'Radicales'hidroxilo'(•OH)' ''

' ' ' ' ' '''''mieloperoxidasa'(MPO)'

' ' ' ' ' '''''halógenos'

' ' 'estables'haloaminas'(cloramina)'

120'RTA'

Mecanismos&de&muerte&intracelular&dependientes&de&oxígeno(

121(RTA(

Mecanismos&de&muerte&dependientes&de&O2.'

•  Intermediarios'ReacDvos'de'Nitrógeno'(RNI)''

–  a'parDr'de'O2'y'L)arginina'

–  sintasa'del'óxido'nítrico'(iNOS)'•  enzima'inducible'

•  Radicales'de'peroxinitritos'(•NOOO)'

–  (•NO)+'(•O2))''

–  para'eliminar'organismos'que'escapan'del'fagosoma'

•  invaden'el'citosol'

122'RTA'

Mecanismos&Independientes&de&O2(

– Catepsinas(– Defensinas(de(bajo(peso(molecular(

– Proteínas(caDónicas(de(alto(peso(molecular(

– Permeability(Increasing(Protein((BPI)(

– Lisozima(

– Lactoferrina(– Enzimas(proteolíDcas(

123(RTA(

Mecanismos&Independientes&de&Oxígeno'

124'RTA'

Células&Citotóxicas(

Células(NK((natural'killer)'

 Linfocitos(grandes((granulares)(

 Reconocen(células(infectadas(con(virus((receptores)(

  Inducen(apoptosis((PCD)( FasL(se(une(al(receptor(Fas(en(la(célula(blanco(

 Degranulación(( Perforinas( TNFβ( Granzimas( ATP(ionizado(

 inducen(apoptosis(

125(RTA(

matan celulas w estan infectadas, le salen senales en la superficies.•

Ellas matan a la celula pero las d alrededor no se afectan, el atp ionizadp hace q halla ‣apoptosis.

126'RTA'

Todo lonq liberan los macrofagos. Sirven d semales•

128'RTA'

129(RTA(

****Aprenderse las marcadas****

130'RTA'

131(RTA(

Stos mismo sreceptores los encontramos en los macrofagos ‣

InfecDon(triggers(an(inflammatory(response.(

•  Macrophages(encountering(bacteria(or(other(types(of(microorganisms(in(Dssues(are(triggered(to(release(cytokines(that(increase(the(permeability(of(blood(vessels,(allowing(fluid(and(proteins(to(pass(into(the(Dssues.(They(also(produce(chemokines,(which(direct(the(migraDon(of(neutrophils(to(the(site(of(infecDon.((

•  The(sDckiness(of(the(endothelial(cells(of(the(blood(vessel(wall(is(also(changed,(so(that(cells(adhere(to(the(wall(and(are(able(to(crawl(through(it;(first(neutrophils(and(then(monocytes(are(shown(entering(the(Dssue(from(a(blood(vessel.((

•  The(accumulaDon(of(fluid(and(cells(at(the(site(of(infecDon(causes(the(redness,(swelling,(heat,(and(pain(known(collecDvely(as(inflammaDon.(Neutrophils(and(macrophages(are(the(principal(inflammatory(cells.((

PAMPs- pathogen associated molecular patterns‣

Innate'RecogniDon'of'Microbes'

Video