???s?a?t?d?as? - ???s??atast??? st??

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???s?a?t?d?as? - ???s??atast??? st?? µetaµ?s?e?s?
s???et?? ?st??

• ?. G. ?????fa?

????a, 2015-2016
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?d?a?te??t?te? t?? s???et?? ?st??

• ?e???aµί??e? p?????? ?st??? (d??µa, µ?e?, ??p??,
  ?eµfad??e?, ?st?, ??p)
• ???e ??a? ??e? d?af??et???? ίa?µ??
  a??s???????t?ta
• ? a??s???????t?ta t?? s???et?? ?st?? ??? e??a?
  ?????sµa t?? ep?µ????? ?st??
• ?? d??µa ??e? t? µe?a??te?? a??s???????t?ta
• ? a???µ? a?t?????pa???s?ast???? ??tt????
• ?????? pa?a???????s?
• ?e???aµί??e? ?eµfad??e? ?a? µ?e?? t?? ?st??

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• Types of Transplant
• Autograft is self-tissue transferred from one
  body site to another in the same individual.
• Isograft is tissue transferred between
  genetically identical individuals.
• Allograft is tissue transferred between
  genetically different members of the same
  species.
• Xenograft is tissue transferred between different
  species

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???s??????? ap??t?s?
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??e???p???s? ? ?eµf???tt????
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????ap????s?

• ???s??????? ap????s? ??a?t? µ?s?e?µat??
• ??a?t?
• ?S? (?µµes? a???a?t?d?as?)
• ??a??et??? ? p???µ??f?sµ?
• ???ss??a a?t????a
• ??µµat??? ?S? epe?e??asµ??a pa???s?asµ??a ap?
  ?S? t?? ??pt? (?µµes? a???a?t?d?as?)
• ? d?ast???t?ta ?s??? ( ap????s? ??a?t?
  pa???????)

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Incidence of Renal Allograft Survival in
Influenced by HLA Matching
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Direct and Indirect Recognition
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????ap????s?-Te???a ??tt????-ep?ίat??

• Passenger cells
• APCs µ?s?e?µa ? ?eµfad??e? ?e?e???p???s? ? ?
  ??a??? a??s???????? ap??t?s?? ? ap??????
  µ?s?e?µat??

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?p??????

• ?pe???e?a ap??????
• ?ept? ??e?
• ????p?????ta a?t?s?µata d??t?
• ??e?a ap??????
• ?µ??e? eίd?µ?de?
• ????d?ast??? ? ?eµf???tta?a
• ?????a ap??????
• ???e? ?????a
• ?p?f?a?? a?µ?f???? a??e???
• ?????? µ??a??sµ??

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?p????? ?ef????? µ?s?e?µat??
??e?a
?????a
?pe???e?a
??e?a
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?pe???e?a ap?????
1. ???s??µat?sµ??a a?t?s?µata, 2. s?µp????µa,
3. ??dete??f??a, 4. f?e?µ???, 5. ???µί?s?
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??e?a ap??????

1. T-?eµf???tta?a, µa???f??a, a?t?s?µata,
2. ???ί? e?d??????? ?a? µ????tt????,
3. F?e?µ???

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?????a ap??????

1. Ma???f??a T ?eµf???tta?a
2. ?pe?p?as?a µ?s?? ??t??a
3. ?????a a?t?d?as? t?p?? ?V

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?????a ap??????

• ?a?d??
• ?ef???
• p?e?µ??e?
• ?pa?
• ???s?, a??e?a??? d?ata?a???, ap??e?a ?e?t?????a?

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St????

• ?p?f??? ap???????
• ? s??ta???asµa ?S? (e??ta?? a??? ap??a??)
• ???s??atast???
• ?pa???? a????? (tolerance)

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???s??atast???

• G???????t???e?d? (GC)
• ??ast??e?? ?a?s??e??????
• ?????sp?????
• Tacrolimus
• ??t?p???ap?as?ast???
• ????fa??????? ???
• ??a?e??p????
• ?apaµ????? (sirolimus)

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G???????t???e?d?

• ???se?? GC
• ? pa?a???? ??tta??????? (IL-1, -6, -3, -4, TNFa,
  GMCSF)
• ?PLPA2, COX2 ? ? PG, LTA
• ? µ???a p??s?????s?? ? ? d?ape?at?t?ta a??e???
• ? e?d??????e?se? ? epa???? ap?pt?s?? se
  ?ef???tta?a ??s???f??a

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??ast??e?? ?a?s??e??????

• Cyclosporin A (fungus Tolyplocladium infatum)
• Tacrolimus (bacterium Streptomyces tsukabaensis)
• ??ast??? t?? d?ast????t?ta? f?sfat?s?? t?? Ca
  e?a?t?µe??? e???µ?? ?a?s??e?????
• ?????p???s? ? ? ? e?d???tt????? Ca ?
  e?e???p???s? ?a?s??e?????? ? e?e???p???s?
  ????d??? IL-2, CD40L, FasL
• ????a d??s? a?ast??? p???ap?as?asµ?? ?
  ?eµf???tt????
• ??ep???µ?te? e????e?e? ?ef??t?????t?ta,
  ?p??tas?, ?pe???p?da?µ?a, ?pe??????a?µ?a,
  ?p?µa???s?aµ?a, ?pe?t????s?, ?pe?p?as?a ?????, G?
  d?ata?a???, ?e???t?????t?ta
• K????sp????? Vs Tacrolimus ? ?ef??t?????t?ta
  a??? ? ??sa?e??a st? G??????

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??t?p???ap?as?ast???

• ?apaµ?????
• Bacterium Streptomyces hygroscopicus on Easter
  island (Rapa ui)
• ?p?t??pe? t?? e?e???p???s?-a?ast???e? t??
  p???ap?as?asµ?
• S??d?eta? µe t?? immunophilin FKBP-12 ? a?ast???
  t?? ????s?? mTOR ? a?ast??? p???ap?as?asµ?? ?
• ??ep???µ?te? e????e?e?
• ?atast??? µ?e???
• ?pe???p?da?µ?a
• Posttransplant Lymphoproliferative Disorders
  (PTLD)
• ?? ?ef??t?????

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??t?p???ap?as?ast???

• ????fa??????? ???
• ?p?????e? t? ????µ? enzyme inosine monophosphate
  dehydrogenase (IMPDH) ??a t? s???es? t?? p???????
• G? d?ata?a???, d??????e?
• A?a?e??p????
• ??ta????st?? t?? p???????
• G? d?ata?a???, ???µ??e??, ?pat?t?????t?ta

?a ta??tata p???ap?as???µe?a ?eµf???tta?a ?????
a????? ap? pa?a???? p??????? ??a s???es? RNA DNA
?a?a???????s? WBC PLT ???? µ?e??t?????t?ta?
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???s??????? a???? (tolerance)
?? a?t?d?as? se s???e???µ??? a?t?????
?e?t????
?e??fe????

• ??????? e???e??? (??µ?? ad??a?)
• ?eµf???tt???? p?? a?a?????????
  ?s???? a?t?a?t????a
• ???sa?µ??? ?p?d???a (µ?e??? t?? ?st??)
• ?????e?a
• a???a??t?ta t?? ??tt???? ?a a?t?d???? sta
  d?e?e?t??? µ???µata
• ep??eta? ap? a?epa??? e?e???p???s? (???e???
  s??d?e?e?t???? µ???µ?t??)

• ???pt??? a?t????a
• ???µµ??a st? es?te???? t?? ?st??, ??tt???? ?
  p??te????
• ?pa???? ??tta????? ?a??t?? ap? ? e?e???p???s?
  (clonal exhaustion)
• ? ???µ?st??? ??tta?a
• IL-10, TGF-ί
• ??t??p? t?? a??s???????? ap????s??
• Th1 ? Th2

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????? ?a? µetaµ?s?e?s?
St?? a??s?????a µetaµ?s?e?se?? e?????µe t?? µ?
a?a??a??t?ta ??a epa???st?? a??s??atast???
(pe??p?? a????)

• ?????? pe??fe????

• ?????? pe??fe????

• ?atast??f? ??

• ?p??????sµa
• s??d?e?e?t???? µ???µ?t??

• ?pa???? ????µ?st???? ??tt????

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??????????? ??t?s?µata

• ATG
• ???s?p???s? ???? µe a????p??a ??µ???tta?a ?
  a?t?s?µata st??e???? a?t????a ?? ? ?atast??f? ??
• ??ep???µ?te? e????e?e?
• ?????s?a
• cytokine release syndrome
• ? ???d???? posttransplant lymphoproliferative
  disorder (PTLD)
• NOT ? infections

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?????????????t?s?µata

• ??t?-IL2Ra
• ?a µ? e?e???p???µ??a ? a??pafa
• ????te?? ap?te?esµat???
• ????te?e? a?ep???µ?te? e????e?e?

• ??t?-CD3
• ?p?te?esµat???
• Cytokine release syndrome
• PTLD

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?????????????t?s?µata

• ??t?-CD40L
• ? ???µί?eµί????? epe?s?d?a

• CTLA-4

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?????????????t?s?µata

• ??t?-CD52
• CD52 d?de?apept?d?? st?? ep?f??e?a µ???p??????
  ??tt????
• ??s? ??tt???? µ?s? s?µp????µat??

S?µpe?asµat??? ta a?t?s?µata, a? ?a? p??? t?
pa??? de? ????? ?p??atast?se? t??? a?ast??e??
?a?s??e?????? ?a? ta GC, d???e???? se a??a?e?
?atast?se??, ?p?? se a??e?t??? se ???a f??µa?a
ap??????
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Te?ape?t??? s??µa

• S????e? s??µa
• ?????? ?e?ape?a (10-15µ??e?)
• ??????????? ? µ?????????? a?t?s?µata
• Te?ape?a d?at???s??
• G???????t???e?d? a?ast??e?? ?a?s??e??????
  a?t?p???ap?as?ast???

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?e?µe??sµ??

• ???s???tta?a d?t? s???pa????? µe a??s???tta?a
  d??t? st?? d??t?
• ?atast??f? a???d?ast???? ?eµf???tt???? t?? d??t?,
  ta ?p??a a????? ?a st??f??ta? e?a?t??? t??
  µ?s?e?µat??
• ???s??? st? d?at???s? ?s????p?a?
• ???s???tta?a d?t? µp??e? ?a st?af??? st? de?t?!!

GVHD
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??s?? µ?s?e?µat?? ??a?t? ?e??st? (GVHD)

• ????p???se??
• ???s??e?et???? d?af???? µeta?? d?t?-??pt?
• ?pa???? a???µ?? a??s???tt???? µ?s?e?µat??
• Passenger leukocytes
• ?eµfad??e?
• ??e?? t?? ?st??
• ??????? e????a
• ?e?µat??? e?a???µata
• ??te???
• G? p????, d??????e?, a?µa

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• ?a ?f??? ap? t? µetaµ?s?e?s? ?st?? ?a p??pe? ?a
  e??a? µe?a??te?a ap? t??? p??a???? ???d????? t??
  a??s??atast????

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Take-home messages

• ????a a??s??????? ap????s? ap? ta ? ?. ??a?t? ???
  (?S?)
• ??? ?????? d??µ?? a??s??atast??? ?a? epa????
  a?????
• ?a? t? µ?s?e?µa µp??e? ?a ep?te?e? st? d?t?!