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RESPONS IMUN T ERHADAP HELMINTH

RESPONS IMUN T ERHADAP HELMINTH. Yoes Prijatna Dachlan Facult as Kedokteran Universitas Wijaya Kusuma Surabaya. (YPD/06.201 4 ). Multiseluler , berukuran besar , tidak selalu bermultiplikasi didalam tubuh host.

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RESPONS IMUN T ERHADAP HELMINTH

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  1. RESPONS IMUN TERHADAP HELMINTH Yoes Prijatna Dachlan Facultas Kedokteran Universitas Wijaya Kusuma Surabaya (YPD/06.2014)

  2. Multiseluler, berukuranbesar, tidakselalubermultiplikasididalamtubuh host Sekalipunhelminthlebihmudahdiaksesolehsistemimun → penderitamasihmengandungsejumlahkecilparasit (carrier) Sistemimunmemberikanperlawanan yang tidakkuat → derajatimunitasterhadaphelminthseringkalisangatlemah HELMINTHS Nematodamempunyaikutikulatebal → melindungi nematode dariefektoksikresponsimun Tegumenschistosomatebalsebagaisaranaproteksi Mantel permukaanhelminthtersebutdapatmengelupas (slough off) ketikamendapatseranganimun •Tapeworms elastase inhibitorelastasenetrofil •Mengembangkanmetodauntukmenghalangioxidative burst •Helminth → sekresi protease → memecahmolekul antibody (imunoglobulin) (Yoes Prijatna Dachlan, 2014)

  3. MORFOLOGI PARASIT NEMATODA Kutikula Hipodermis Otot Traktus digestivus Sistem syaraf Sistem ekskretori Sistem reproduktif Bentuk larva TREMATODA Tegumen Traktus digestivus Sistem syaraf dan otot Osmoregulatory system Sistem reproduktif CESTOIDEA Tegumen Parenchyme Otot parenchym Scolex Calcareous corpuscle Osmoregulatory system System syaraf Sistem reproduktif (Yoes Prijatna Dachlan 2014)

  4. The functions of tegument TREMATODA CESTOIDEA Microthrix (microvilli) provide resistance to the peristaltic movement of the intestine Glycocalyx (a surface layer of carbohydrate) protecting the parasite from host digestive enzymes, enhancing nutrient absorption, and maintaining the parasite’s surface membrane Proximal cytoplasm (cyton) involved in protein synthesis and packaging Tegumental musculature consisting of an outer and inner layer with its contractile fibrils • A dynamic, cellular structure, a generally homogenous layer • Glycocalyx (surface coat) : to absorb exogenous molecules. Hydrolytic enzymatic activity facilitates the uptake of certain molecules from the environment. Also a protective structure, shielding the worm from host antibodies and digestive enzymes • Spine : may serve as ancillary holdfast mechanisms; storage sites for certain essential molecules • Proximal cytoplasm for the repair and maintenance of the distal cytoplasm (Yoes Prijatna Dachlan 2014)

  5. Cuticle • Lapisan elastis menyelaputi permukaan nematoda. Tidak semata-mata sebagai lapisan pembungkus tetapi juga melakukan metabolisme aktif karena mengandung enzym • Umumnya permukaan kutikula halus, tetapi pula mengandung berbagai struktur, seperti spina, papila, dll. • Terdiri dari 4 lapisan : - epi-kutikula : pelindung - exo-kutikula : terdiri dari 2 sublayer, eksternal dan internal - meso-kutikula : fleksibel untuk memudahkan kesemua arah dan tebalnya menunjukkan umur cacing - endo-kutikula (Yoes Prijatna Dachlan 2014)

  6. IMMUNITY TO PARASITES (1) • Memahami imunologipenyakit parasitikyang penting gunamengendalikanpenyakittersebutmelalui imunisasi • Mempelajari respons host terhadap parasit yang kemudian penting untuk lebih memahamitentang respons imun itu sendiri. Contoh : For studying the formation and regulation of granulomatous inflammation Response to schistosome eggs Schistosomula as in vitro experimental model For elucidating the function of eosinophil (Yoes Prijatna Dachlan 2014)

  7. Schistosoma species Egg Delayed-type hypersensitivity An inflammatory granuloma forms with epithelial, giant, plasma and eosinophil cells and fibroblasts. There is subsequent fibrosis and calcification (Chiodini, Moody, Manser, 2001) Atlas of Med .Helminth. & Protozool. (Yoes Prijatna Dachlan 2014)

  8. Helminthdapatmengaktifkankomplemenjaluralternatif • Molekul permukaan parasit mengikat C3b dan selanjutnya komplemen jalur alternatif teraktifkan dan berakhir dengan lisisnya membran permukaan parasit Polysaccharide constituents of the parasites express at their outer surfaces and bind the C3b Polisakarida pada permukaan parasit Factor D Factor B C3  C3b C3bBb C3bBb3b C3 C3b C3 C5b C5 - 9 MAC C6 C7 C8 C9 • C3b selalu dibentuk secara berkesinambungan di sirkulasi (serum) oleh C3 konvertase (enzim pemecah C3 menjadi C3b). • MAC ( Membrane attack complex ) : gabungan komponen komplemen C5, C6, C7, C8, C9 menyebabkan osmotic lysis dari sel-sel permukaan parasit YPD/2014

  9. INNATE IMMUNITY TERHADAP PARASIT • Parasitdapatmengaktifkankomplemenjaluralternatif. • Parasitdapatmenghindardarilisisolehaktivasikomplemenjaluralternatif • dengancaraparasitmenghilangkanmolekulpermukaannyasendirisehingga • tidakterjadipengikatan C3b, danselanjutnyamencegahaktivasikomplemen • jaluralternatif. • Ataudengancara lain, permukaanparasitmenyerap protein hospes yang • berperansebagai regulator, seperti DAF ( decay accelerating factor ). • D. DAF menghambatikatan C3b dengan Bb, sehinggatidakterbentukenzim C3bBb • (pemecah C3 menjadi C3b). dengandemikianlysispermukaanparasittercegah. • Beberapa protozoa tahanterhadapfagositikmakrofag, bahkanparasit • memperbanyakdiri di dalammakrofag. • Tegumenhelminthtahanterhadapmekanismesitosidal ( cytocidal ) neutrofildan • makrofag. Golongan protozoa danhelminth yang memasukitubuhhospesmelaluialirandarahdanjaringanseringkalimampubertahanhidupdankemudianmelakukanreplikasi, inikarenaparasitberhasilmenyesuaikandiridenganbaikdalammempertahankandiriterhadappertahananalamihospes

  10. HOST PROTEIN: DAF Decay accelerating factor C3b + Bb 1 3 DAF 2 C3bBb PARASITE (Yoes Prijatna Dachlan, 2014)

  11. Respons imunterwujuduntukmelawanSchistosoma mansoni (KUBY) (Yoes Prijatna Dachlan, 2014)

  12. Pertahanan untuk melawan infeksi helminth → diperantarai oleh aktivasi TH2 cells → yang menghasilkan produksi antibodi IgE dan aktivasi eosinofil ADCC (Yoes Prijatna Dachlan, 2014)

  13. Trichinella spralis larva + Eosinophil + Specific Antibodies (Virella G., Tomlinson S., 2007) Medical Immunology 6th Ed (Yoes Prijatna Dachlan, 2014)

  14. EXPULSION OF INTESTINAL WORMS • It depends on Th2 responses and requires the coordinated action of : • Antibody : IgG and IgE • The release of mucin by cytokine-stimulated Goblet. cells • The production of intestinal contraction and diarrhea by mast cell mediators (Roitt IM, et al., 2011) (Yoes Prijatna Dachlan 09/06/2014)

  15. Helminths Naive cell Epitope DC PRR IL-4 IL-9 Il-5 Il-13 T Th2 TCR MHC class II PAMPs Development of the immune response to helminth (Male, Brostov, Roth, Roitt, 2006) (Yoes Prijatna Dachlan, 2014)

  16. reseptorinnate yang terlibat dalam mengenal parasit (Male, Brostoff, Roth, Roitt, 2006) (Yoes Prijatna Dachlan, 2014)

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