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Prof Dr Ariyanto Harsono dr SpAK
CURICULUM VITAE
Tempat /tgl lahir : Kediri, 3- Juli
Agama : Islam
Status Perkawinan: Menikah
Pendidikan
S-1: Lulus Dokter : FK UNAIR, 1972
S-2: Spesialis Anak : FK UNAIR, 1982
S-3: Program Pascasarjana UNAIR, 2004
Pendidikan tambahan : Sertifikat “Fellowship on Food Allergy”,
Academisch Ziekenhuis Utrecht, Nederland, 1990-1991
Jabatan sekarang : Guru Besar Ilmu Kesehatan Anak,
Dep IKA FK UNAIR/RSU Dr.Soetomo, Surabaya.
Konsultan Alergi/Imunologi: 1992
1
Symbiotic: Manfaat Lebih Untuk
Kasus Alergi Pada Anak
Prof DR Dr Ariyanto Harsono SpA(K)
PENDAHULUAN
• Mikrobiota pada usus manusia terdiri atas
beberapa ratus spesies, banyak diantaranya
yang sangat bermanfaat. Misalnya untuk
mencegah kolonisasi kuman patogen dan
memelihara integritas imunitas mukosa usus.
• Sebaliknya, sistem imun mukosa usus sehat
memungkinkan bertahannya mikrobiota usus
dan menghindari toleransi imunologi,
mempertahankan homeostasis usus.
3Prof DR Dr Ariyantto Harsosno SpA(K)
Ag
APC MHC-II Th0
IL-12/ IL-1
Th-2
Th.1
IL-1
TNF-β, IFN-γ
IL-2, IFN-γ
B-Cell
IL-4
IL-5
SEL PLASMASEL MEMORI
IL-6
IL-10
CTL
MHC-I
I L-2
IFN-γ
SEL-NK
SEL-NK AKTIF
FC-R
L
L
SEL ABNORMAL
SITOTOKSIN
SEL-LISIS
Sel Abnormal FASL
Memory Cells
ADCC
4Prof DR Dr Ariyantto Harsosno SpA(K)
Probiotic
Treg
TGFβ
• Prebiotik yang banyak dikenal dan digunakan
adalah oligosakarida kedelai (yang terdiri atas
rafinosa dan stakiosa), frukto-oligosakarida
(disebut juga oligofruktosa), Inulin, Laktulosa
dan Laktosukrosa. Inulin dan oligofruktosa
memiliki fungsi penting sebagai penyeimbang
fungsi gastrointestinal (menyeimbangkan
mikroflora kolon).
5Prof DR Dr Ariyantto Harsosno SpA(K)
Metabolisme Prebiotik--> Short Chain Fatty Acid
6Prof DR Dr Ariyantto Harsosno SpA(K)
Prebiotik membantu mengatasi
kerusakan barier mukosa usus
• Prebiotik
fructooligosaccharides (FOS)
dan inulin merupakan substrat
untuk fermentasi mikrobiota
usus proximal dan distal
• Fermentasi FOS dan inulin di
kolon menghasilkan short-
chain fatty acids (SCFA)¹
• SCFAs merupakan pelumas
untuk epitel ileum dan kolon,
yang membantu memelihara
integritas dinding kolon²
7Prof DR Dr Ariyantto Harsosno SpA(K)
Prebiotik membantu pertumbuhan flora
normal usus:
• Fermentasi FOS dan inulin
menghasilkan lactic acid4
• Lactic acid membantu
menurunkan pH kolon,
menyebabkan kolon kurang
baik untuk pertumbuhan
pathogenic bacteria2,4
• FOS dan inulin secara selektif
mempermudah pertumbuhan
bacteria yang baik dengan
dosis 8 gram per hari2-4,5
• Lactate membantu
menurunkan pH kolon untuk
mengontrol pertumbuhan
bacteria patogen
8Prof DR Dr Ariyantto Harsosno SpA(K)
Meta analisis kegunaan Synbiotik
9Prof DR Dr Ariyantto Harsosno SpA(K)
PROBIOTIK
NON PATOGENIK
• Probiotik adalah mikroorganisme hidup yang
berasal dari tumbuhan. Mereka pada
dasarnya adalah ganggang. Bakteri probiotik
hadir di usus sejak manusia lahir. Bakteri ini
terus menerus mengalahkan mikroba lain
dalam tubuh, dan hal ini dapat dapat
mengancam populasinya. Selain itu,
pengobatan antibiotik dapat membunuh
semua bakteri dalam tubuh, termasuk
bakteri probiotik. 10Prof DR Dr Ariyantto Harsosno SpA(K)
Mikroflora Usus
11Prof DR Dr Ariyantto Harsosno SpA(K)
Non Pathogenic bacteria Pathogenic bacteria
12Prof DR Dr Ariyantto Harsosno SpA(K)
13Prof DR Dr Ariyantto Harsosno SpA(K)
Bagaimana bacteria intra luminal
membangkitkan respons imun sistemik?:
• (A) Fluoresensi di Peyer's
patches usus halus
• (B) Fluoresensi di lamina
propria usus halus
• (C) Fluoresensi di nodule
dan crypta usus besar
14Prof DR Dr Ariyantto Harsosno SpA(K)
Internalisasi bacteria kedalam GI
Sebagian mikrobiota difagosit dan dimusnahakan. Sebagian epitopnya dibantu dengan IL6
menimbulkan clonal IgA B lymphocytes, meningkatkan jumlah IgA-producing cells dan transfer ke
plasma sel usus. IL-6 bersama dengan IL-4 dan TGF-ß dapat menginduksi T-independent switch dari IgM
ke IgA dipermukaan sel B.
(EC, intestinal epithelial cells; MQ, macrophages; TL, T lymphocytes; BL, B lymphocytes; MS, mast cells;
PC, plasma cells).
15Prof DR Dr Ariyantto Harsosno SpA(K)
Prof DR Dr Ariyantto Harsosno SpA(K) 16
Prof DR Dr Ariyantto Harsosno SpA(K) 17
Schematic representation of the multiple consequences of the cross-talk between the
probiotic bacteria and the intestinal mucosa.
Corthésy B et al. J. Nutr. 2007;137:781S-790S
©2007 by American Society for Nutrition
18Prof DR Dr Ariyantto Harsosno SpA(K)
Treg
19Prof DR Dr Ariyantto Harsosno SpA(K)
20Prof DR Dr Ariyantto Harsosno SpA(K)
IgA
TReg
TGF−β
21Prof DR Dr Ariyantto Harsosno SpA(K)
Cara kerja antibodi yang di-induksi
Probiotik
22Prof DR Dr Ariyantto Harsosno SpA(K)
Orihara et. al. WAO Journal 2008, 9-14
The profiles of immune
response in healthy subject
23Prof DR Dr Ariyantto Harsosno SpA(K)
The
balancing
square
model.
The 4 T-cell
types (Th1,
Th2, Th17,
and Treg)
antagonize
each other.
Proinflammatory T-cell
subsets, that is, Th17 cells and
Th2 cells that are capable of
producing high levels of TNF-
> (iTh2 cells) are upregulated
Th2 cells that are capable of
producing IL-10 (rTh2 cells)
may be up-regulated, and
Th17 cells may be inactivated
Orihara et. al. WAO Journal 2008, 9-14
The profiles of immune response in
symptomatic & asymptomatic atopy
24Prof DR Dr Ariyantto Harsosno SpA(K)
25Prof DR Dr Ariyantto Harsosno SpA(K)
WHAT ARE IMMUNOMODULATION INDUCED BY PROBIOTICS?
Organism days No. of cells producingb
:
Cytokines
IgA
TNF- a IFN- g IL-2 IL-12 IL-4 IL-10
L. casei
CRL 431
2 90 ± 8* 124 ± 15* 24 ± 6 13 ± 3 86 ± 23* 40 ± 2* 99 ± 21
L.
delbrueckii
subsp.
bulgaricus
CRL 423
2 79 ± 6* 59 ± 22* 40 ± 8 23 ± 11 67 ± 4* 85 ± 9* 135 ± 23*
L.
acidophilu
s CRL 724
7 Strains
2
2
52 ± 7
98+/-8
51 ± 25*
165+/-34
27 ± 8
50+/-23
30 ± 16*
45+/-60
44 ± 11
30+/-46
30 ± 7
90+/-54
173 ± 24*
199+/-76
Control 2 24 ± 4 17 ± 6 31 ± 12 11 ± 2 27 ± 7 18 ± 6 98 ± 17
26Prof DR Dr Ariyantto Harsosno SpA(K)
Probiotic modulation of humoral
immunity
Bifido
bacterium
bifidus, (live)
Human Total IgA and
response to
polio virus
Increased
sIgA
27Prof DR Dr Ariyantto Harsosno SpA(K)
Effects of probiotics on nonspecific
immunity
Probacteria Species Assessment Effect
Lactobacillus casei
Shirota, intravenous
Rodent Peritoneal macrophages Increased phagocytosis
L. acidophilus or
Bifidobacterium bifidum,
oral (live)
Rodent Peritoneal or peripheral
blood macrophages
Enhanced phagocytosis
L. acidophilus or casei,
oral (live)
Rodent Resident peritoneal
macrophages
Enhanced phagocytosis
L. casei Shirota
7 strains oral (live)
Human
Peripheral blood No effect on natural killer
cell cytolysis in vitro
Enhanced phagocytosis
28Prof DR Dr Ariyantto Harsosno SpA(K)
Effect of probiotics on select human
disease1
Disease Probiotic Assessment Effect
Asthma Lactobacillus
acidophilus, oral
(live)
Serum IgE and IL-4
Lymphocyte
proliferation
No alterations
Rotavirus infection 7 starins, oral (live) Diarrhea Serum
total IgA and IgM
and anti-rotavirus
IgM and IgG
Duration of
diarrhea decreased;
Increased anti-
rotavirus IgA
Atopic Dermatitis L. casei, oral (live) Anti-ß-lactoglobulin
IgA- secreting cells
Number increased
Clinical
improvement 29Prof DR Dr Ariyantto Harsosno SpA(K)
Synbiotic dalam pencegahan
Asthma
• Bayi dengan Dermatitis Atopika lebih sering
menderita Asthma.
• Pemberian Synbiotic pada bayi-bayi
Dermatitis Atopika mencegah terjadinya
Asthma pada masa naka-anak.
(van der Aa LB, Synbiotics prevent asthma-like symptoms in infants with
atopic dermatitis, Allergy, 2011:68:170-7)
30Prof DR Dr Ariyantto Harsosno SpA(K)
Regulator Treg
• Probiotic untuk
penderita alergi,
Inflammatory Bowel
Disease, auto imun
membangkitkan
keseimbangan kearah
Treg melalui resptor TLR2,
TLR4, TLR6.
(Rook GAW: microbes,
immunoregulation, and
Gut.accessed fromProf DR Dr Ariyantto Harsosno SpA(K) 31
PROBIOTIC
IgA
Menurunkan kejadian penyakit
alergi
• Probiotic Menyebabkan Keseimbangan
intestinal dan sistem imun menurunkan
kejadian penyakit alergi.
(Hormannsperger G: Gut matters: microbe-host interactions in allergic
disease. J Allergy clin Immunol 2012;129:1452-9)
32Prof DR Dr Ariyantto Harsosno SpA(K)
Meningkatkan CD4 T limfosit
• Probiotic merangsang
klonal CD4 T limfosit
berperan dalam
perbaikan penyakit
alergi.
(Mazmanian SK: The love–hate
relationship between bacterial
polysaccharides and the host
immune system. Nature Reviews
Immunology, 2006: 6, 849-858)
Prof DR Dr Ariyantto Harsosno SpA(K) 33
Kegunaan Probiotik
34Prof DR Dr Ariyantto Harsosno SpA(K)
35Prof DR Dr Ariyantto Harsosno SpA(K)
36Prof DR Dr Ariyantto Harsosno SpA(K)
Dasar pemilihan Probiotik
37Prof DR Dr Ariyantto Harsosno SpA(K)
TH1<Treg <TH2
TH1 > Treg > TH2
TH1, Treg and TH2 immunoregulation through TLR2 and TLR4 by
Lactobacillus plantarum IS-10506 probiotics in reducing allergic
reaction. Experimental Study in Mice Subjects
Allergic
Reaction
Adaptive
Immunity
Innate
Immunity
Control group LIS probiotics group
(Endaryanto A, et.al., 2006)Study on animal model
38Prof DR Dr Ariyantto Harsosno SpA(K)
RANKof
FEV1rev
RANKof
Eo_count
RANKofIgE
RANKofIL5
RANKofIL4
RANKofIL10
RANKofTGFb
RANKofIFNg
RANKofIL2
55
50
45
40
35
30
25
20
15
Mean
post-treatment with SLIT
Treg
TH2
Sym
TH1
RANKof
FEV1rev
RANKof
Eo_count
RANKofIgE
RANKofIL5
RANKofIL4
RANKofIL10
RANKofTGFb
RANKofIFNg
RANKofIL2
55
50
45
40
35
30
25
20
15
Mean
post-treatment with probiotics
Treg
Sym
TH1
TH2
Probiotics compared with SLIT in influencing
the Treg–mediated balance shift of TH1-TH2 in
children with allergic-asthma.
Fig 1. FEV1 reversibility in % of predicted normal
value, total IgE, eosinophil count, IFN-γ, IL-2, IL10,
TGF-β, IL-4, and IL-5
in the post-treatment condition with SLIT
Fig 2. FEV1 reversibility in % of predicted normal
value, total IgE, eosinophil count, IFN-γ, IL-2, IL10,
TGF-β, IL-4, and IL-5
in the post-treatment with probiotics
39Prof DR Dr Ariyantto Harsosno SpA(K)
RANKof
FEV1rev
RANKof
Eo_count
RANKofIgE
RANKofIL5
RANKofIL4
RANKofIL10
RANKofTGFb
RANKofIFNg
RANKofIL2
55
50
45
40
35
30
25
20
15
Mean
RANKof
FEV1rev
RANKof
Eo_count
RANKofIgE
RANKofIL5
RANKofIL4
RANKofIL10
RANKofTGFb
RANKofIFNg
RANKofIL2
55
50
45
40
35
30
25
20
15
Mean
pre-treatment post-treatment with probiotics
Treg
Sym
TH1
TH2
(Endaryanto A, Harsono A, 2006)Study on pediatric subjects
The different of probiotics and SLIT in
influencing the Treg–mediated balance shift of
TH1-TH2 in children with allergic-asthma.
40Prof DR Dr Ariyantto Harsosno SpA(K)
Thank You41Prof DR Dr Ariyantto Harsosno SpA(K)

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Immunomodulation induced by symbiotic

  • 1. Prof Dr Ariyanto Harsono dr SpAK CURICULUM VITAE Tempat /tgl lahir : Kediri, 3- Juli Agama : Islam Status Perkawinan: Menikah Pendidikan S-1: Lulus Dokter : FK UNAIR, 1972 S-2: Spesialis Anak : FK UNAIR, 1982 S-3: Program Pascasarjana UNAIR, 2004 Pendidikan tambahan : Sertifikat “Fellowship on Food Allergy”, Academisch Ziekenhuis Utrecht, Nederland, 1990-1991 Jabatan sekarang : Guru Besar Ilmu Kesehatan Anak, Dep IKA FK UNAIR/RSU Dr.Soetomo, Surabaya. Konsultan Alergi/Imunologi: 1992 1
  • 2. Symbiotic: Manfaat Lebih Untuk Kasus Alergi Pada Anak Prof DR Dr Ariyanto Harsono SpA(K)
  • 3. PENDAHULUAN • Mikrobiota pada usus manusia terdiri atas beberapa ratus spesies, banyak diantaranya yang sangat bermanfaat. Misalnya untuk mencegah kolonisasi kuman patogen dan memelihara integritas imunitas mukosa usus. • Sebaliknya, sistem imun mukosa usus sehat memungkinkan bertahannya mikrobiota usus dan menghindari toleransi imunologi, mempertahankan homeostasis usus. 3Prof DR Dr Ariyantto Harsosno SpA(K)
  • 4. Ag APC MHC-II Th0 IL-12/ IL-1 Th-2 Th.1 IL-1 TNF-β, IFN-γ IL-2, IFN-γ B-Cell IL-4 IL-5 SEL PLASMASEL MEMORI IL-6 IL-10 CTL MHC-I I L-2 IFN-γ SEL-NK SEL-NK AKTIF FC-R L L SEL ABNORMAL SITOTOKSIN SEL-LISIS Sel Abnormal FASL Memory Cells ADCC 4Prof DR Dr Ariyantto Harsosno SpA(K) Probiotic Treg TGFβ
  • 5. • Prebiotik yang banyak dikenal dan digunakan adalah oligosakarida kedelai (yang terdiri atas rafinosa dan stakiosa), frukto-oligosakarida (disebut juga oligofruktosa), Inulin, Laktulosa dan Laktosukrosa. Inulin dan oligofruktosa memiliki fungsi penting sebagai penyeimbang fungsi gastrointestinal (menyeimbangkan mikroflora kolon). 5Prof DR Dr Ariyantto Harsosno SpA(K)
  • 6. Metabolisme Prebiotik--> Short Chain Fatty Acid 6Prof DR Dr Ariyantto Harsosno SpA(K)
  • 7. Prebiotik membantu mengatasi kerusakan barier mukosa usus • Prebiotik fructooligosaccharides (FOS) dan inulin merupakan substrat untuk fermentasi mikrobiota usus proximal dan distal • Fermentasi FOS dan inulin di kolon menghasilkan short- chain fatty acids (SCFA)¹ • SCFAs merupakan pelumas untuk epitel ileum dan kolon, yang membantu memelihara integritas dinding kolon² 7Prof DR Dr Ariyantto Harsosno SpA(K)
  • 8. Prebiotik membantu pertumbuhan flora normal usus: • Fermentasi FOS dan inulin menghasilkan lactic acid4 • Lactic acid membantu menurunkan pH kolon, menyebabkan kolon kurang baik untuk pertumbuhan pathogenic bacteria2,4 • FOS dan inulin secara selektif mempermudah pertumbuhan bacteria yang baik dengan dosis 8 gram per hari2-4,5 • Lactate membantu menurunkan pH kolon untuk mengontrol pertumbuhan bacteria patogen 8Prof DR Dr Ariyantto Harsosno SpA(K)
  • 9. Meta analisis kegunaan Synbiotik 9Prof DR Dr Ariyantto Harsosno SpA(K)
  • 10. PROBIOTIK NON PATOGENIK • Probiotik adalah mikroorganisme hidup yang berasal dari tumbuhan. Mereka pada dasarnya adalah ganggang. Bakteri probiotik hadir di usus sejak manusia lahir. Bakteri ini terus menerus mengalahkan mikroba lain dalam tubuh, dan hal ini dapat dapat mengancam populasinya. Selain itu, pengobatan antibiotik dapat membunuh semua bakteri dalam tubuh, termasuk bakteri probiotik. 10Prof DR Dr Ariyantto Harsosno SpA(K)
  • 11. Mikroflora Usus 11Prof DR Dr Ariyantto Harsosno SpA(K)
  • 12. Non Pathogenic bacteria Pathogenic bacteria 12Prof DR Dr Ariyantto Harsosno SpA(K)
  • 13. 13Prof DR Dr Ariyantto Harsosno SpA(K)
  • 14. Bagaimana bacteria intra luminal membangkitkan respons imun sistemik?: • (A) Fluoresensi di Peyer's patches usus halus • (B) Fluoresensi di lamina propria usus halus • (C) Fluoresensi di nodule dan crypta usus besar 14Prof DR Dr Ariyantto Harsosno SpA(K) Internalisasi bacteria kedalam GI
  • 15. Sebagian mikrobiota difagosit dan dimusnahakan. Sebagian epitopnya dibantu dengan IL6 menimbulkan clonal IgA B lymphocytes, meningkatkan jumlah IgA-producing cells dan transfer ke plasma sel usus. IL-6 bersama dengan IL-4 dan TGF-ß dapat menginduksi T-independent switch dari IgM ke IgA dipermukaan sel B. (EC, intestinal epithelial cells; MQ, macrophages; TL, T lymphocytes; BL, B lymphocytes; MS, mast cells; PC, plasma cells). 15Prof DR Dr Ariyantto Harsosno SpA(K)
  • 16. Prof DR Dr Ariyantto Harsosno SpA(K) 16
  • 17. Prof DR Dr Ariyantto Harsosno SpA(K) 17
  • 18. Schematic representation of the multiple consequences of the cross-talk between the probiotic bacteria and the intestinal mucosa. Corthésy B et al. J. Nutr. 2007;137:781S-790S ©2007 by American Society for Nutrition 18Prof DR Dr Ariyantto Harsosno SpA(K) Treg
  • 19. 19Prof DR Dr Ariyantto Harsosno SpA(K)
  • 20. 20Prof DR Dr Ariyantto Harsosno SpA(K)
  • 21. IgA TReg TGF−β 21Prof DR Dr Ariyantto Harsosno SpA(K)
  • 22. Cara kerja antibodi yang di-induksi Probiotik 22Prof DR Dr Ariyantto Harsosno SpA(K)
  • 23. Orihara et. al. WAO Journal 2008, 9-14 The profiles of immune response in healthy subject 23Prof DR Dr Ariyantto Harsosno SpA(K)
  • 24. The balancing square model. The 4 T-cell types (Th1, Th2, Th17, and Treg) antagonize each other. Proinflammatory T-cell subsets, that is, Th17 cells and Th2 cells that are capable of producing high levels of TNF- > (iTh2 cells) are upregulated Th2 cells that are capable of producing IL-10 (rTh2 cells) may be up-regulated, and Th17 cells may be inactivated Orihara et. al. WAO Journal 2008, 9-14 The profiles of immune response in symptomatic & asymptomatic atopy 24Prof DR Dr Ariyantto Harsosno SpA(K)
  • 25. 25Prof DR Dr Ariyantto Harsosno SpA(K)
  • 26. WHAT ARE IMMUNOMODULATION INDUCED BY PROBIOTICS? Organism days No. of cells producingb : Cytokines IgA TNF- a IFN- g IL-2 IL-12 IL-4 IL-10 L. casei CRL 431 2 90 ± 8* 124 ± 15* 24 ± 6 13 ± 3 86 ± 23* 40 ± 2* 99 ± 21 L. delbrueckii subsp. bulgaricus CRL 423 2 79 ± 6* 59 ± 22* 40 ± 8 23 ± 11 67 ± 4* 85 ± 9* 135 ± 23* L. acidophilu s CRL 724 7 Strains 2 2 52 ± 7 98+/-8 51 ± 25* 165+/-34 27 ± 8 50+/-23 30 ± 16* 45+/-60 44 ± 11 30+/-46 30 ± 7 90+/-54 173 ± 24* 199+/-76 Control 2 24 ± 4 17 ± 6 31 ± 12 11 ± 2 27 ± 7 18 ± 6 98 ± 17 26Prof DR Dr Ariyantto Harsosno SpA(K)
  • 27. Probiotic modulation of humoral immunity Bifido bacterium bifidus, (live) Human Total IgA and response to polio virus Increased sIgA 27Prof DR Dr Ariyantto Harsosno SpA(K)
  • 28. Effects of probiotics on nonspecific immunity Probacteria Species Assessment Effect Lactobacillus casei Shirota, intravenous Rodent Peritoneal macrophages Increased phagocytosis L. acidophilus or Bifidobacterium bifidum, oral (live) Rodent Peritoneal or peripheral blood macrophages Enhanced phagocytosis L. acidophilus or casei, oral (live) Rodent Resident peritoneal macrophages Enhanced phagocytosis L. casei Shirota 7 strains oral (live) Human Peripheral blood No effect on natural killer cell cytolysis in vitro Enhanced phagocytosis 28Prof DR Dr Ariyantto Harsosno SpA(K)
  • 29. Effect of probiotics on select human disease1 Disease Probiotic Assessment Effect Asthma Lactobacillus acidophilus, oral (live) Serum IgE and IL-4 Lymphocyte proliferation No alterations Rotavirus infection 7 starins, oral (live) Diarrhea Serum total IgA and IgM and anti-rotavirus IgM and IgG Duration of diarrhea decreased; Increased anti- rotavirus IgA Atopic Dermatitis L. casei, oral (live) Anti-ß-lactoglobulin IgA- secreting cells Number increased Clinical improvement 29Prof DR Dr Ariyantto Harsosno SpA(K)
  • 30. Synbiotic dalam pencegahan Asthma • Bayi dengan Dermatitis Atopika lebih sering menderita Asthma. • Pemberian Synbiotic pada bayi-bayi Dermatitis Atopika mencegah terjadinya Asthma pada masa naka-anak. (van der Aa LB, Synbiotics prevent asthma-like symptoms in infants with atopic dermatitis, Allergy, 2011:68:170-7) 30Prof DR Dr Ariyantto Harsosno SpA(K)
  • 31. Regulator Treg • Probiotic untuk penderita alergi, Inflammatory Bowel Disease, auto imun membangkitkan keseimbangan kearah Treg melalui resptor TLR2, TLR4, TLR6. (Rook GAW: microbes, immunoregulation, and Gut.accessed fromProf DR Dr Ariyantto Harsosno SpA(K) 31 PROBIOTIC IgA
  • 32. Menurunkan kejadian penyakit alergi • Probiotic Menyebabkan Keseimbangan intestinal dan sistem imun menurunkan kejadian penyakit alergi. (Hormannsperger G: Gut matters: microbe-host interactions in allergic disease. J Allergy clin Immunol 2012;129:1452-9) 32Prof DR Dr Ariyantto Harsosno SpA(K)
  • 33. Meningkatkan CD4 T limfosit • Probiotic merangsang klonal CD4 T limfosit berperan dalam perbaikan penyakit alergi. (Mazmanian SK: The love–hate relationship between bacterial polysaccharides and the host immune system. Nature Reviews Immunology, 2006: 6, 849-858) Prof DR Dr Ariyantto Harsosno SpA(K) 33
  • 34. Kegunaan Probiotik 34Prof DR Dr Ariyantto Harsosno SpA(K)
  • 35. 35Prof DR Dr Ariyantto Harsosno SpA(K)
  • 36. 36Prof DR Dr Ariyantto Harsosno SpA(K)
  • 37. Dasar pemilihan Probiotik 37Prof DR Dr Ariyantto Harsosno SpA(K)
  • 38. TH1<Treg <TH2 TH1 > Treg > TH2 TH1, Treg and TH2 immunoregulation through TLR2 and TLR4 by Lactobacillus plantarum IS-10506 probiotics in reducing allergic reaction. Experimental Study in Mice Subjects Allergic Reaction Adaptive Immunity Innate Immunity Control group LIS probiotics group (Endaryanto A, et.al., 2006)Study on animal model 38Prof DR Dr Ariyantto Harsosno SpA(K)
  • 39. RANKof FEV1rev RANKof Eo_count RANKofIgE RANKofIL5 RANKofIL4 RANKofIL10 RANKofTGFb RANKofIFNg RANKofIL2 55 50 45 40 35 30 25 20 15 Mean post-treatment with SLIT Treg TH2 Sym TH1 RANKof FEV1rev RANKof Eo_count RANKofIgE RANKofIL5 RANKofIL4 RANKofIL10 RANKofTGFb RANKofIFNg RANKofIL2 55 50 45 40 35 30 25 20 15 Mean post-treatment with probiotics Treg Sym TH1 TH2 Probiotics compared with SLIT in influencing the Treg–mediated balance shift of TH1-TH2 in children with allergic-asthma. Fig 1. FEV1 reversibility in % of predicted normal value, total IgE, eosinophil count, IFN-γ, IL-2, IL10, TGF-β, IL-4, and IL-5 in the post-treatment condition with SLIT Fig 2. FEV1 reversibility in % of predicted normal value, total IgE, eosinophil count, IFN-γ, IL-2, IL10, TGF-β, IL-4, and IL-5 in the post-treatment with probiotics 39Prof DR Dr Ariyantto Harsosno SpA(K)
  • 40. RANKof FEV1rev RANKof Eo_count RANKofIgE RANKofIL5 RANKofIL4 RANKofIL10 RANKofTGFb RANKofIFNg RANKofIL2 55 50 45 40 35 30 25 20 15 Mean RANKof FEV1rev RANKof Eo_count RANKofIgE RANKofIL5 RANKofIL4 RANKofIL10 RANKofTGFb RANKofIFNg RANKofIL2 55 50 45 40 35 30 25 20 15 Mean pre-treatment post-treatment with probiotics Treg Sym TH1 TH2 (Endaryanto A, Harsono A, 2006)Study on pediatric subjects The different of probiotics and SLIT in influencing the Treg–mediated balance shift of TH1-TH2 in children with allergic-asthma. 40Prof DR Dr Ariyantto Harsosno SpA(K)
  • 41. Thank You41Prof DR Dr Ariyantto Harsosno SpA(K)

Editor's Notes

  1. Schematic representation of the multiple consequences of the cross-talk between the probiotic bacteria and the intestinal mucosa. At the intestinal epithelial level, probiotic bacteria may allow beneficial effects through transient colonization and/or release of bioactive compounds. This translates into reinforcement of the intestinal barrier as well as direct modulation of epithelial cell functions including cytokine and chemokine release. Although a limited event, translocation of bacteria to the lamina propria may affect innate and adaptive immunity by activating production of cytokines by monocytes/macrophages. Sampling by M cells in Peyer&apos;s patches ( PP ) and subsequent engulfment by dendritic cells ( DC ) of the innate immune system may contribute to present microbial antigens to naïve T cells in the PP and mesenteric lymph nodes ( MLN ). This allows IgA antibody-mediated mucosal response to take place against the bacterium to prevent overgrowth and spreading beyond MLN but also, for example, to the antigen coded by a recombinant probiotic strain used as a vaccine. Remarkably, the same processing pathway plays a critical role in the shaping of the mucosal immune system toward a noninflammatory, tolerogenic pattern that takes place through the induction of regulatory T cells. Author&apos;s caution: The scheme is a simplified synthesis obtained from data collected in vivo and in vitro in various experimental models; the specific effects of a particular probiotic on the development of local and systemic responses must be considered on a case-by-case basis.