RESPONS IMUN TERHADAP

PROTOZOA
Yoes Prijatna Dachlan
Facultas Kedokteran
Universitas Wijaya Kusuma Surabaya

June 2014
 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
Protozoan diseases
•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)
 ANTIBODY SINGLE ACTION

Infected Red Blood Cells at schizont stage

. .
. . .. . . .
. .

Prevents spread by neutralizing attachment site

(Yoes Prijatna Dachlan, 2014)

 ~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
(Abbas, Lichtman, Pillai, 2010)

(Yoes Prijatna Dachlan, 2014)

 The way by which protozoa that multiply within macrohages escape
digestion by lysosomal enzymes

Toxoplasma
gondii
MØ
.
.
Parasit tetap hidup
didalam endosome –
(tidak terjadi fusi
dengan lysosome)

.
Lysosom
e

Parasit mati didalam

fagosom yang telah
berfusi dengan (Male, Brostov, Roth, Roitt, 2006)
lysosom

(Yoes Prijatna Dachlan, 2014)4)

Mechanism of INNATE
Complement
Classical
Lectin receptors pathway

Ab Lectin
C1 pathway
Macrophage C4-C2
Alternative
TLRs pathway
C3b opsonization

PAMP

scavenger receptors
(Male, Brostoff, Roth, Roitt, 2006)

protozoan

(Yoes Prijatna Dachlan, 2014)

 Steps of the three complement activation
pathways

(Yoes Prijatna Dachlan, 2014)

 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 IFN-γ Produce IL-4
↓ ↓
Activate MØ MØ-suppressive actions
↓ of Th-2
Destroy intracellular ↓
parasites Increased parasite survival
and excerbation of lesions

(Yoes Prijatna Dachlan, 2014)

 IL-12
Naive cell
PRR DC
T Th1 IFNγ
MHC class TCR IL-2
Protozoa II

Development of the immune response to protozoan

(Male, Brostov, Roth, Roitt, 2006)

Yoes Prijatna Dachlan 2014
 Immune Responses to Disease-Causing Protozoan

PROTOZOA DISEASES Principal mechanisms of

protective immunity
Plasmodium species Malaria Abs and CD8+ CTLs
Leishmania donovani Leishmanisis CD4+ Th1 cells activate MØ
(mucocutaneous, to kill phagocytosed parasites
disseminated)
Trypanosoma brucei African trypanosomiasis Abs
Entamoeba Amebiasis Abs, phagocytosis
histolytica

Abbas, Lichtman, Pillai, 2010. Cellular and molecular immunology

(Chiodini, Moody, Manser, 2001)Atlas of Med .Helminth.& Protozool.

(Yoes Prijatna Dachlan 2014)

 reseptor innate yang terlibat dalam mengenal parasit

FAMILY MEMBER PARASITE LIGAND

Collectins MBL Mannose-rich sugars from numerous
protozoans
Pentraxins CRP Phospholipids and phosphosugars
Leishmania spp
C-type lectins MØ mannose receptor Trypanosoma cruzy
Scavenger receptors CD36 P. falciparum (PfEMP1)
C’ receptor CR1/CR3 Leishmania spp. lipophosphoglycan
TLRs TLR2 (with GPI anchors from many protozoans
TLR1/TLR6)
TLR9 Protozoal DNA
Malaria pigment hemozoin

(Male, Brostoff, Roth, Roitt, 2006)

(Yoes Prijatna Dachlan 2014)

Entamoeba histolytica penyebab amoebiasis
Invasi kedalam usus besar

(Yoes Prijatna Dachlan, 2014) (PL Chiodini, AH Moody, DW Manser, 2003)

 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)
 Malaria transmission cycle from mosquito
to human

(Yoes Prijatna Dachlan, 2012

 The identification proteins of a malarial
parasite

(Marcus B, 2009)
Marcus B. Deadly diseases and
epidemics. Malaria,2009.
Yoes Prijatna Dachlan,2010
 Abs
CD8+ T cell
Hepatic stage
Sporozoite LSA
CSP SALSA
TRAP
STARP

Abs

Merozoite
AMA-1
EBA175 Ring trophozoite
Pf RH1/2/3/4
MSP1/2/3 RESA
RAP1/2
GLURP
NK and
~Species specific immunity
CD4+ T cell
~Stage specific immunity
~Antigenic diversity
~Geographic origin
~Polyclonal B cell activation Schizonts
PfEMP-1 Gametocyte
Rifins Pfg27
STEVOR Pfg230
HRP-2 Pfg48/45

Abs (Kinyanjui, 2012)

• 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)

PfEMP1 on knob structure

(Yoes Prijatna Dachlan, 2014)

(Yoes Prijatna Dachlan, 2014)
 GPI

, Lymphotoxin

(Yoes Prijatna Dachlan, 2014)