peningkatan respon imun adaptif pada asosiasi dengan infeksi
TRANSCRIPT
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
1/24
PENINGKATAN RESPON IMUN ADAPTIF
PADA ASOSIASI DENGAN INFEKSI LATEN
Wuchereria bancrofti
Seminar 1
Agus Jaya/1106152413/guru
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
2/24
Pendahuluan
Di dunia terdapat 1,3 miliar penduduk yang berisiko tertularpenyakit kaki gajah di lebih dari 83 negara dan 60% kasusberada di Asia Tenggara.1,10
filariasis di dunia menghabiskan dana 5 juta US$ setiap tahun
untuk penanggulangannnya dan menduduki ranking 3 setelahmalaria dan tuberculosis.3
WHO: The Global Goal of Elimination of Lymphatic Filariasisas a Public Health Problem by the Year 2020.
Lebih dari 90% infeksi ini ditimbulkan oleh Wucheriabancroftidan cacing dewasa berada dalam sistem limfatikmelepaskan jutaan mikrofilaria (MF), yang secara periodikberedar dalam darah.4
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
3/24
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
4/24
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
5/24
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
6/24
FIGURE 109 Functions of TH2 cells. CD4+ T cells that differentiate into TH2 cells secrete IL-4, IL-5, and IL-13.
IL-4 (and IL-13) act on B cells to stimulate production of
antibodies that bind to mast cells, such as IgE. IL-4 is also an autocrine growth and differentiation cytokine
for TH2 cells. IL-5 activates eosinophils, a response that is important for defense against helminthic
infections. IL-4 and IL-13 are involved in barrier immunity, induce an alternative pathway of macrophageactivation, and inhibit classical, TH1- mediated macrophage activation.
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
7/24
Respon imun adaptif terhadap cacing
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
8/24
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
9/24
Susceptible, resistance, and pathology
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
10/24
Hasil penelitian(Kathrin Arndts, dkk. Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn,
Germany)2008,Ghana
Responden:
Pria(18-50 th) yg terinfeksi Wb asymptomatic
n=159 97 MF+, 62 MF-
Pembanding 22 orang sehat tanpa infeksi
EN (endemic Normal)
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
11/24
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
12/24
Figure 1. Active circulation of MF is associated with the number of worm nests.
Figure 1. Active circulation of MF is associated with the number of worm nests.
Using ultrasound, infected individuals were examined for (A) the lymph dilation around
the worm nests and (B) for the amount of worm nests (FDS). In addition, patients were
also examined for (C) the maximum degree of their supratesticular lymph dilation,
presented as a staging system. Box whisker plots in (A) show median, interquartile
ranges and outliers of individually tested patients. Bars in (B) and (C) show the number
of individuals and their correlating amount of worm nests or lymph dilation
respectively. Data in (B) were tested for significance with the Cochran-Armitage trend
test (p
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
13/24
Figure 2. Patent infection alters filarial-specific Th2-like responses.
Arndts K, Deininger S, Specht S, Klarmann U, et al. (2012) Elevated Adaptive Immune Responses Are Associated with Latent Infections of
Wuchereria bancrofti. PLoS Negl Trop Dis 6(4): e1611. doi:10.1371/journal.pntd.0001611
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611 -
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
14/24
Figure 2. Patent infection alters filarial-specific Th2-like responses.
Isolated PBMCs (2105/well) from endemic controls (EN) or filarial-
infected MF+ or MF patients were stimulated with either anti-CD3/anti-
CD28 (10 g/ml/2.5 g/ml; A and E), Brugia malayiextract (B.m., 5 g/ml;B and F), MSP-1 0.25 g/ml; C and G) or LPS (50 ng/ml; D and H) for 72
hours. Thereafter, levels of IL-5 (AD) or IL-13 (EH) were measured in the
culture supernatants via ELISA. Graphs show box whiskers with median,
interquartile ranges and outliers after background subtraction. Statistical
significances between the indicated groups were obtained after Kruskal-Wallis and Mann-Whitney-U tests.
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
15/24
Figure 3. Latent infected patients show elevated IL-17 but not Th1-like responses.
Arndts K, Deininger S, Specht S, Klarmann U, et al. (2012) Elevated Adaptive Immune Responses Are Associated with Latent Infections of
Wuchereria bancrofti. PLoS Negl Trop Dis 6(4): e1611. doi:10.1371/journal.pntd.0001611
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611 -
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
16/24
Figure 3. Latent infected patients show elevated IL-17 but not Th1-like
responses.
Isolated PBMCs (2105/well) from endemic controls (EN) or MF+ or
MF patients suffering from LF were stimulated with either anti-CD3/anti-
CD28 (10 g/ml/2.5 g/ml; A and E), Brugia malayiextract (B.m. 5 g/ml; B
and F), MSP-1 (0.25 g/ml; C and G) or LPS (50 ng/ml; D and H) for 72
hours. Thereafter, levels of IFN- (AD) or IL-17 (EH) were measured in the
culture supernatants via ELISA. Graphs show box whiskers with median,interquartile ranges and outliers after background subtraction. Statistical
significances between the indicated groups were obtained after Kruskal-
Wallis and Mann-Whitney-U tests.
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
17/24
Figure 4. Regulatory responses are enhanced in latently infected individuals.
Arndts K, Deininger S, Specht S, Klarmann U, et al. (2012) Elevated Adaptive Immune Responses Are Associated with Latent Infections of
Wuchereria bancrofti. PLoS Negl Trop Dis 6(4): e1611. doi:10.1371/journal.pntd.0001611
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611 -
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
18/24
Figure 4. Regulatory responses are enhanced in latently infected
individuals.
Isolated PBMCs from endemic controls (EN) or patients infected with W.
bancroftiwere stimulated with anti-CD3/anti-CD28 (10 g/ml/2.5 g/ml; A,E), Brugia malayiextract (5 g/ml, B, F), MSP-1 (0.25 g/ml; C, G) or LPS
(50 ng/ml, D, H) for 72 hours. Thereafter, culture supernatant was tested
via ELISA for cytokine release of IL-10 and IL-6. Graphs show box whiskers
with median, interquartile ranges and outliers after background
subtraction. Statistical significances between the indicated groups wereobtained after Kruskal-Wallis and Mann-Whitney-U tests.
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
19/24
Figure 5. Circulating microfilariae dampen release of TNF.
Figure 5. Circulating microfilariae dampen release of TNF.
Isolated PBMCs from endemic controls (EN) or patients suffering from LF were stimulated with
anti-CD3/anti-CD28 (10 g/ml/2.5 g/ml; A), Brugia malayiextract (5 g/ml; B), LPS (50 ng/ml;C) or with MSP-1 (0.25 g/ml; D) for 72 hours. Thereafter, culture supernatant was tested via
ELISA for cytokine release of TNF. Graphs show box whiskers with median, interquartile ranges
and outliers after background subtraction. Statistical significances between the indicated
groups were obtained after Kruskal-Wallis and Mann-Whitney-U tests.
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
20/24
Figure 6. Patently infected individuals present elevated levels of total IgE.
Arndts K, Deininger S, Specht S, Klarmann U, et al. (2012) Elevated Adaptive Immune Responses Are Associated with Latent Infections of
Wuchereria bancrofti. PLoS Negl Trop Dis 6(4): e1611. doi:10.1371/journal.pntd.0001611
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611
http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0001611 -
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
21/24
Figure 6. Patently infected individuals present elevated levels of total IgE.
Plasma from all three groups was analyzed for the production of total IgG1
(A), IgG2 (B), IgG3 (C), IgG4 (D) and IgE (E) with the Cytometric Bead Array.
(F) shows the ratio of IgG4 and IgE. Graphs show box whiskers with median,interquartile ranges and outliers. Statistical significances between the
indicated groups were obtained after Kruskal-Wallis and Mann-Whitney-U
tests.
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
22/24
Figure 7. Patent infected patients produce more filarial-specific IgG4.
Figure 7. Patent infected patients produce more filarial-specific IgG4.
Plasma from all participants was investigated for the presence of helminth-specific
immunoglobulins by ELISA. Plates were coated overnight with 5 g/ml B.m. extract in PBS (pH
= 9.6), incubated with patient and control plasma overnight and analyzed for specific IgG1-4
and IgE. Presented are the ratios of antigen-specific antibodies IgG4/IgE (A), IgG4/IgG1 (B),IgG4/IgG2 (C) and IgG4/IgG3 (D). Graphs show box whiskers with median, interquartile ranges
and outliers. Statistical significances between the indicated groups were obtained after
Kruskal-Wallis and Mann-Whitney-U tests.
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
23/24
Kesimpulan Secara ringkas, setelah dibandingkan dengan individu MF+, pasien
amikrofilaremia menunjukkan profil peningkatan TNF, IL-17, IL-10, IL-6 dan
respon filarial-spesifik Th2-like. Ditemukan pula bahwa usia tidakberkorelasi dengan peningkatan produksi sitokin, tetapi status infeksilah
yang menentukan profil kekebalan tubuh.
Pola imunosupresif pada pasien MF + dilengkapi dengan rasio tinggi
IgG4/IgE tertentu. Prevalensi IgG4 memberikan perlindungan untuk host
dan parasite, karena menyediakan mekanisme untuk melawan- mengaturtinggi IgE dan dengan demikian menghindari immunopatologi yang
berlebihan. Perbedaan antara kedua kelompok yang terinfeksi, yang tidak
menderita patologi klinis, menunjukkan bahwa keberadaan mikrofilaria
tampak relevan untuk menginduksi imunosupresi.
Penemuan ini memberikan wawasan baru dalam individu amikrofilaremiaasimptomatik, dimana sebelumnya pasien ini diabaikan. Respon kekebalan
tinggi mereka dapat memberikan kunci pada eludasi alternative terapi
pengobatan yang diharapkan dapat memblokir penularan/transmisi yang
berakibat dapat membasmi/eradikasi infeksi/penyakit.4
-
7/29/2019 Peningkatan Respon Imun Adaptif Pada Asosiasi Dengan Infeksi
24/24
DAFTAR PUSTAKA
1. Subdit Filariasis Kemenkes RI. Rencana Nasional Program Akselerasi Eliminasi Filariasis Di
Indonesia 2010-2014.Jakarta:April 2010.
2. Alam A, Garna H. Buku Ajar Divisi Infeksi Dan Penyakit Tropis. Jakarta: Sagung Seto, 2012.3. Jan H.F.(et.al) Strategic emphases for tropical diseases research: a TDR perspective.TRENDS in
Parasitology Vol.18 No.10 October 2002.
4. Arndts K, Deininger S, Specht S, Klarmann U, Mand S, et al. (2012) Elevated Adaptive Immune
Responses Are Associated with Latent Infections of Wuchereria bancrofti. PLoS Negl Trop Dis
6(4): e1611. doi:10.1371/journal.pntd.000161
5. Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. Ed.6. Philadelphia:Saunders Elsevier, 2010.
6. Bratawijaya KG, Rengganis I. Imunologi Dasar. Edisi 10. Jakarta: Badan Penerbit FKUI, 2012.
7. Kresno SB. Imunologi: diagnosis dan prosedur laboratorium. Edisi 5. Jakarta: Badan Penerbit
FKUI, 2010.
8. Sutanto I, Ismid IS, Syarifudin PK, Sungkar S. Buku ajar parasitology kedokteran. Edisi ke 4.
Jakarta: Badan Penerbit FKUI, 2008.9. Nutman TB, Kazura JW. Filariasis. Dalam Guerrant RL. et al. Tropical Infectious Diseases. (e-book)
10. WHO. Weekly epidemiological record: Global programme to eliminate lymphatic filariasis:
progress report 2011, 14 september 2012, 87th year. No. 37, 2012, 87, 345356