Imunitas dan Patogen Parasit

1. ImunitasdanPatogenParasit Yoes Prijatna Dachlan Fakultas Kedokteran Universitas Wijaya Kusuma Surabaya Juni 2014

2. Eukaryotic pathogens Unicellular protozoans ~sebagian protozoa replikasisecara ekstraseluler ~sebagianlainnya replikasisecara intraseluler Multicellular helminth worms ~Helminth worms reproduksidalamtubuh host~ataudiluartubuh host disuatulokasidimana parasitmudahmengaksess host ~Pertumbuhan dan maturasicacingterjadi didalamtubuhhost → severe and long- term damage to tissues and organs Parasites Umumnya, cell-mediated immunity dan humoral immunitydimobilisasiuntukmenaklukan parasit (Yoes Prijatna Dachlan, 2014)

3. Most parasites represent complex life cycles • Part of which occurs in humans (or other vertebrates) • Part of which occurs in intermediate hosts (flies, ticks, snails) There is a considerable problem from a public health point of view, since a parasite that continually changes form and/or makes use of an invertebrate or animal vector is much harder to control than a pathogen that infects human only (Yoes Prijatna Dachlan, 2014)

4. Protozoan infections (Kaufmann, 2011) (Yoes Prijatna) Dachlan, 2014)

5. Trematoda •Schistosoma spp. hati, intestine, bladder, paru → fibrosis •Opistorchis spp. → livercancer (O. viverrini) •Fasciola hepatica → liver Cestoda •Echinococcus spp. hatidanjaringanlainnya •Taeniasolium → otak Platyhelminths s Nematodes Filariae •Brugiamalayi lymphatics → elephantiasis •Wuchereriabancrofti lymphatics→ elephantiasis •Onchocerca volvulus → kulit, mata Soil transmitted nematodes •Ancylostomaduodenale → intestin (anemia) •Necatoramericanus → intestin (anemia) •Trichuristrichiura → intestin •Strongyloidesstercoralis → intestin •Ascarislumbricoides → intestin (Kaufmann, 2011) (Yoes Prijatna Dachlan, 2014)

6. Umumnya infeksi menjadi khronis karena : • Lemahnya Innate Immunity • Kemampuan parasit menghindar atau bertahan terhadap daya eliminasi Adaptive Immune Response • Individu yang tinggal di daerah endemis seringkali mendapat paparan (terus menerus), sehingga memerlukan kemoterapi yang berulang  mahal • Vaksin yang efektif belum berhasil ditemukan. Vaksin malaria sangat dibutuhkan sehubungan dengan meluasnya resistensi parasit didunia terhadap obat antimalaria. (Yoes Prijatna Dachlan, 2014)

7. Respons imun terhadap struktur antigenik yang kompleks mempunyai manifestasi yang bervariasi dan tidak selalu mewujudkan kekebalan yang mampu melindungi hospes dengan sempurna (complete protective immunity) • Respons imun seringkali pada kasus-kasus penyakit infeksi menghasilkan penyakitnya menjadi lebih serius dibandingkan dengan yang diakibatkan oleh parasit itu sendiri • Beberapa parasit mampu menghindar dari respons imun dengan menggunakan mekanisme yang bervariasi • Kemampuan parasit beradaptasi dengan lingkungan hospesnya menyebabkan parasit tetap berhasil mempertahankan hidupnya (Yoes Prijatna Dachlan, 2014)

8. Persistence, Chronicity and Evasion • Most parasitic infections are chronic in nature • Chronicity is evidence that the immune response has failed to eradicate the infection and implies that the immune responses to most parasites are to some extent ineffectual • A consequence of chronicity is the presence of regulatory mechanisms that develop to modulate immunologically mediated tissue damage associated with infection (Yoes Prijatna) Dachlan, 2014)

9. denganmenghindardariresponsimun(melaluiantigenic variationatau mekanismelainnya) Parasit mengembangkansuatuperlawananterhadapresposimun atau, mencegahberkembangnya mekanisme efektor kedua strategi diatasdipakai Host meresponskuathanyaterhadap antigen yangdiekspresikanpadastadiumitusaja Setiap stadium parasit mengekspresikan gen yang spesifikterhadap stadium respons terhadap antigentersebuttidakefektipuntukmelawan stadium parasit → infeksimenjadikhronis (Yoes Prijatna) Dachlan, 2014) (Kaufmann, 2011)

10. √Although parasitism implies mutual coexistence of host and infectious agent, the immune response plays a critical role in the establishment and maintenance of this balance √Traditionally, the control of parasitic infections was thought to be the exclusive domain of the acquired immune system and typical innate functions ~Complement components ADAPTIVE TRADITIONAL CONCEPT + PARASITES Typical Innate (Hunter & Sher, 2011) ~Phagocytes ~Complemen components Primitive vector mechanisms (Yoes Prijatna Dachlan, 2014)

11. √Since the start of the 1990s, it has been recognized that the early interactions between the host innate system and pathogens shape subsequent adaptive responses and the outcome of infection CONCEPT of 1990s Host Innate System ADAPTIVE Outcome of Infection + PARASITES RESOLUTION DISEASE LATENCY (Yoes Prijatna Dachlan, 2014)

12. Innate Immunity to Parasitic Infections Humoral mechanisms Cellular mechanisms In Determining the Nature of Adaptive Immunity Molecular Basis for Innate Recognition Activation of Complement Mediated by Phagocytes PAMPs & PRRs (eg. TLR) Involve sharply divergent T-cell effector outcomes • Th1/Th2 • a balanced immune response • Tregs Development of IFN-γ Granulocyte populations (Eo, mastocytes) (Kaufmann, 2011) (Hunter CA; Sher A) (Yoes Prijatna Dachlan, 2014)

13. Adaptive Immunity to Parasitic Infections Intracellular Parasites of Phagocytic Cells (Leishmania, T.gondii, T. cruzi) Initiation of immunity TLR → DCs → cytokine IL-12 T-cell dependent Control Activation of MØ and DCs The key cytokines important for resolution is IFN-γ (Kaufmann, 2011) (Scott P., Riley EM) (Yoes Prijatna Dachlan, 2014)

14. Mechanic and chemical barrier MØ Neu NK B1 B cells Tγδ cells Innate immune system DC MØ Tαβ cells Tαβ cells B2 B cells Adaptive immune system (Yoes Prijatna Dachlan,2013)