Imunitas dan patogen parasit
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Imunitas dan Patogen Parasit. Yoes Prijatna Dachlan Fakultas Kedokteran Universitas Wijaya Kusuma Surabaya. Juni 2014. Eukaryotic pathogens. Unicellular protozoans. ~s ebagian protozoa repli k a si secara e ks tra s elul er ~ sebagian lainnya repli kasi secara intra seluler.

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Imunitas dan Patogen Parasit

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Imunitas dan patogen parasit

ImunitasdanPatogenParasit

Yoes Prijatna Dachlan

Fakultas Kedokteran

Universitas Wijaya Kusuma Surabaya

Juni 2014


Imunitas dan patogen parasit

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)


Most parasites represent complex life cycles

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)


Imunitas dan patogen parasit

Protozoan infections

(Kaufmann, 2011)

(Yoes Prijatna) Dachlan, 2014)


Imunitas dan patogen parasit

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)


Umumnya infeksi menjadi khronis karena

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)


Imunitas dan patogen parasit

  • 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)


Persistence chronicity and evasion

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)


Imunitas dan patogen parasit

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)


Imunitas dan patogen parasit

√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)


Imunitas dan patogen parasit

√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)


Imunitas dan patogen parasit

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)


Imunitas dan patogen parasit

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)


Imunitas dan patogen parasit

Mechanic and

chemical barrier

Neu

NK

B1 B cells

Tγδ cells

Innate immune

system

DC

Tαβ cells

Tαβ cells

B2 B cells

Adaptive immune

system

(Yoes Prijatna Dachlan,2013)


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