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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&aracted&to&wound&area&by&chemotacGc&
factors&of&the&immune&response&or&by&products&of&
bacterial&infecGon.&
112'RTA'
Animacion leucotrinos extravasation (kuby inmunology)•
pare 1:59
Comenzo 2:08
Phagocytosis
C3b
Antibody
Encapsulated
Bacteria
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

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