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RESPONS IMUN TERHADAP PROTOZOA Yoes Prijatna Dachlan Facultas Kedokteran Universitas Wijaya Kusuma Surabaya June 2014.

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Presentasi berjudul: "RESPONS IMUN TERHADAP PROTOZOA Yoes Prijatna Dachlan Facultas Kedokteran Universitas Wijaya Kusuma Surabaya June 2014."— Transcript presentasi:

1 RESPONS IMUN TERHADAP PROTOZOA Yoes Prijatna Dachlan Facultas Kedokteran Universitas Wijaya Kusuma Surabaya June 2014

2 Protozoan diseases Jenis respons imun yang berkembang dan keefektifan respons bergantung dari, a.l. lokasi parasit didalam host Protozoa bisa hidup: didalam usus → amoeba di sirkulasi darah → African trypanosomiasis dalam makrofag → Leishmania spp., Toxoplasma gondii dalam otot → Trypanosoma cruzi Protozoa yang bebas berada di sirkulasi darah selama menjalani siklus hidupnya → humoral antibody yang paling efektif Protozoa yang sedang tumbuh secara intraseluler selama menjalani siklus hidupnya → cell-mediated immune response yang efektif (Yoes Prijatna Dachlan 2014)

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

4 ~Respons imun innate terhadap protozoa yang terpenting adalah fagositosis ~namun banyak protozoa mampu bertahan hidup terhadap efek fagositosis → replikasi dalam sel makrofag ~Protozoa mengekspresikan molekul permukaan yang dikenal oleh TLR/PRR dan kemudian mengaktivasi sel fagosit ~Mekanisme pertahanan yang terpenting dalam melawan protozoa yang hidup dalam makrofag adalah cell-mediated immunity, terutama makrofag yang diaktifkan oleh sitokin yang bersumber dari sel Th1 (Yoes Prijatna Dachlan, 2014 ) (Abbas, Lichtman, Pillai, 2010)

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

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

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 ↓ Produce IFN-γ ↓ Activate MØ ↓ Destroy intracellular parasites Activation of Th-2 by protozoa ↓ Produce IL-4 ↓ MØ-suppressive actions of Th-2 ↓ Increased parasite survival and excerbation of lesions (Yoes Prijatna Dachlan, 2014)

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

10 PROTOZOADISEASESPrincipal mechanisms of protective immunity Plasmodium speciesMalariaAbs and CD8+ CTLs Leishmania donovaniLeishmanisis (mucocutaneous, disseminated) CD4+ Th1 cells activate MØ to kill phagocytosed parasites Trypanosoma bruceiAfrican trypanosomiasisAbs Entamoeba histolytica AmebiasisAbs, phagocytosis Abbas, Lichtman, Pillai, Cellular and molecular immunology (Yoes Prijatna Dachlan 2014) Immune Responses to Disease-Causing Protozoan (Chiodini, Moody, Manser, 2001) Atlas of Med.Helminth.& Protozool.

11 FAMILYMEMBERPARASITE LIGAND CollectinsMBLMannose-rich sugars from numerous protozoans PentraxinsCRPPhospholipids and phosphosugars Leishmania spp C-type lectinsMØ mannose receptorTrypanosoma cruzy Scavenger receptorsCD36P. falciparum (PfEMP1) C’ receptorCR1/CR3Leishmania spp. lipophosphoglycan TLRsTLR2 (with TLR1/TLR6) GPI anchors from many protozoans TLR9Protozoal DNA Malaria pigment hemozoin (Male, Brostoff, Roth, Roitt, 2006) (Yoes Prijatna Dachlan 2014) reseptor innate yang terlibat dalam mengenal parasit

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

13 Malarial Parasites Human Host Immune Response Effective Not effective Pathology Response No Response Anemia Cerebral Malaria Sterilization Hyper-parasitemia Respiratory- of Infection Distress Immune response Parasitemia (Troye-Blomberg, Weidanz, v.d. Heyde, 2005)

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

15 Sporozoite CSP TRAP STARP Hepatic stage LSA SALSA Ring trophozoite RESA Schizonts PfEMP-1 Rifins STEVOR HRP-2 Gametocyte Pfg27 Pfg230 Pfg48/45 ~ Species specific immunity ~ Stage specific immunity ~ Antigenic diversity ~ Geographic origin ~ Polyclonal B cell activation (Kinyanjui, 2012) Merozoite AMA-1 EBA175 Pf RH1/2/3/4 MSP1/2/3 RAP1/2 GLURP Abs CD8+ T cell Abs NK and CD4+ T cell 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: Microvascular cytoadherence/sequestration Pathophysiology 1: Microvascular cytoadherence/sequestration and microvascular obstruction (Yoes Prijatna Dachlan, 2014)

19 Pathophysiology 2: dysregulated inflammatory response GPI, Lymphotoxin (Yoes Prijatna Dachlan, 2014)


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