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RESPONS IMUN T ERHADAP PROTOZOA

RESPONS IMUN T ERHADAP PROTOZOA. Yoes Prijatna Dachlan Facult as Kedokteran Universit as Wijaya Kusuma Surabaya. June 201 4. Jenis respons imun yang berkembang dan keefektifan respons bergantung dari , a.l . lokasi parasit didalam host. Protozoa bisa hidup :

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RESPONS IMUN T ERHADAP PROTOZOA

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  1. RESPONS IMUN TERHADAP PROTOZOA Yoes Prijatna Dachlan FacultasKedokteran Universitas WijayaKusuma Surabaya June 2014

  2. Jenisresponsimun yang berkembangdankeefektifanresponsbergantungdari, a.l. lokasiparasitdidalam host Protozoa bisahidup: • didalamusus → amoeba •di sirkulasidarah → African trypanosomiasis •dalammakrofag →Leishmania spp., Toxoplasma gondii •dalamotot→ Trypanosoma cruzi Protozoan diseases Protozoa yang bebasberada di sirkulasidarahselamamenjalanisiklushidupnya → humoral antibody yang paling efektif Protozoa yang sedangtumbuhsecaraintraselulerselamamenjalanisiklushidupnya → cell-mediated immune response yang efektif (Yoes Prijatna Dachlan 2014)

  3. ANTIBODY SINGLE ACTION Infected Red Blood Cells at schizont stage . . . . . . . . . . . . Prevents spread by neutralizing attachment site (Yoes Prijatna Dachlan, 2014)

  4. ~Responsimuninnateterhadap protozoa yang terpentingadalah fagositosis ~namunbanyak protozoa mampubertahanhidupterhadapefek fagositosis → replikasidalamselmakrofag ~Protozoa mengekspresikanmolekulpermukaan yang dikenal oleh TLR/PRR dankemudianmengaktivasiselfagosit ~Mekanismepertahanan yang terpentingdalammelawan protozoa yang hidupdalammakrofagadalahcell-mediated immunity, terutamamakrofag yang diaktifkanolehsitokin yang bersumberdarisel Th1 (Abbas, Lichtman, Pillai, 2010) (Yoes Prijatna Dachlan, 2014)

  5. The way by which protozoa that multiply within macrohages escape digestion by lysosomal enzymes Toxoplasma gondii . MØ Parasit tetap hidupdidalam endosome – (tidak terjadi fusi dengan lysosome) . . Lysosome Parasit matididalamfagosom yang telahberfusi dengan lysosom (Male, Brostov, Roth, Roitt, 2006) (Yoes Prijatna Dachlan, 2014)4)

  6. Mechanism of INNATE Complement Classical pathway Lectin receptors Lectin pathway Ab C1 Macrophage C4-C2 Alternative pathway TLRs C3b opsonization PAMP scavenger receptors (Male, Brostoff, Roth, Roitt, 2006) protozoan (Yoes Prijatna Dachlan, 2014)

  7. Steps of the three complement activation pathways (Yoes Prijatna Dachlan, 2014)

  8. Leishmania major (in mice), a protozoan that survives within the endosomes of macrophages Activation of Leishmania-specific Th-1 CD4+ T cell Activation of Th-2 by protozoa ↓ Produce IL-4 ↓ MØ-suppressive actions of Th-2 ↓ Increased parasite survival and excerbation of lesions ↓ Produce IFN-γ ↓ Activate MØ ↓ Destroy intracellular parasites (Yoes Prijatna Dachlan, 2014)

  9. IL-12 Naive cell DC PRR T Th1 IFNγ IL-2 TCR MHC class II Protozoa Development of the immune response to protozoan (Male, Brostov, Roth, Roitt, 2006) Yoes Prijatna Dachlan 2014

  10. Immune Responses to Disease-Causing Protozoan Abbas, Lichtman, Pillai, 2010. Cellular and molecular immunology (Chiodini, Moody, Manser, 2001)Atlas of Med .Helminth.& Protozool. (Yoes Prijatna Dachlan 2014)

  11. reseptor innate yang terlibat dalam mengenal parasit (Male, Brostoff, Roth, Roitt, 2006) (Yoes Prijatna Dachlan 2014)

  12. Entamoeba histolytica penyebab amoebiasis Invasi kedalam usus besar (PL Chiodini, AH Moody, DW Manser, 2003) (Yoes Prijatna Dachlan, 2014)

  13. Malarial Parasites Human Host Immune Response EffectiveNot effective Pathology ResponseNo Response •Anemia • Cerebral Malaria SterilizationHyper-parasitemia • Respiratory- of Infection Distress Immune response Parasitemia (Troye-Blomberg, Weidanz, v.d. Heyde, 2005)

  14. The identification proteins of a malarial parasite (Marcus B, 2009) Marcus B. Deadly diseases and epidemics. Malaria,2009. Yoes Prijatna Dachlan,2010

  15. Abs CD8+ T cell Hepatic stage LSA SALSA Sporozoite CSP TRAP STARP Abs Merozoite AMA-1 EBA175 Pf RH1/2/3/4 MSP1/2/3 RAP1/2 GLURP Ring trophozoite RESA NK and CD4+ T cell ~Species specific immunity ~Stage specific immunity ~Antigenic diversity ~Geographic origin ~Polyclonal B cell activation Schizonts PfEMP-1 Rifins STEVOR HRP-2 Gametocyte Pfg27 Pfg230 Pfg48/45 (Kinyanjui, 2012) Abs

  16. Pathophysiology 1 – “Knobs” • Deformation of pRBCs resulting in “knobs” on the RBC surface • Plasmodium falciparum Expressed Membrane Protein (PfEMP1) • Endothelial cell ligands • CD36 • ICAM-1 • VCAM-1 • P-selectin • Chondroitin sulfate A (Yoes Prijatna Dachlan, 2014)

  17. PfEMP1 on knob structure (Yoes Prijatna Dachlan, 2014)

  18. Pathophysiology 1: Microvascularcytoadherence/sequestration and microvascular obstruction (Yoes Prijatna Dachlan, 2014)

  19. Pathophysiology 2: dysregulatedinflammatory response GPI , Lymphotoxin (Yoes Prijatna Dachlan, 2014)

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