Mahardika AWParasitologi- FK UGM

4/3/2013dikafkugm@yahoo.co.id1

4/3/2013 2dikafkugm@yahoo.co.id

The cartoon illustrates the threat to the body from various pathogens (viruses, bacteria, parasites, worms) and the various types of immune responses. The illustration shows leucocytes, which are killing worms, B cells (‘bombers’) which form specific antibodies that destroy bacteria, and cytotoxic T cells (‘police with truncheons’), which destroy virus-infected cells. (© Eric Reits) 4/3/2013 3dikafkugm@yahoo.co.id

4/3/2013 4

Adaptive immunity

Innate immunity

Humoral Immune response

Cellular Immune response

Mucosal Immune response

dikafkugm@yahoo.co.id

Protozoa

Helminth

Arthropod

4/3/2013 5dikafkugm@yahoo.co.id

4/3/2013 dikafkugm@yahoo.co.id 6

4/3/2013 dikafkugm@yahoo.co.id 7

Antigen E. histolitica

20-32 componentSolubleUn-soluble

Surface :12 glycoprotein strong hydrophobicattachment

Somatic

The triad :Gal–lectin, cysteine proteinases and amoebapores major

proteins involved in the pathogenesis of amoebiasis.

Other amoebic molecules:lipophosphopeptidoglycan, perioxiredoxin, arginase, and lysine and glutamicacid-rich proteins are also implicated

8

Attachment

Amoeba’s surface Ag bind to fibronectin & Laminin

Lectin

Matrix extracell:

- Collagen

- Fibronectin

- Laminin

Attachment & Migration into solid tissue

4/3/2013

Surface Ag:-Lectin-Cystein proteinase-Amebaphore

dikafkugm@yahoo.co.id

9

4/3/2013

RELM-β: Resistin like mol β homeostatis of GI & inflamation; TFF3: Trefoil factor Family 3 parameter fungsi sel goblet

Amoebacysteineproteases manipulate and destroy host defences to facilitate nutrient acquisition, parasite colonization and/or invasion.

dikafkugm@yahoo.co.id

10

4/3/2013

Cysteine proteases of the protozoan parasite Entamoebahistolytica are key virulence factors involved in overcoming host defences. These proteases are cathepsin-like enzymes with a cathepsin-L like structure, but cathepsin-B substrate specificity.

In the host intestine, amoeba cysteine proteases cleave colonic mucins and degrade secretory immunoglobulin (Ig) A and IgG rendering them ineffective.

They also act on epithelial tight junctions and degrade the extracellular matrix to promote cell death.

They are involved in the destruction of red blood cells and the evasion of neutrophils and macrophages and they activate pro-inflammatory cytokines IL-1b and IL-18.

Strategies to inhibit the activity of amoeba cysteineproteases could contribute significantly to host protection against E. histolytica. dikafkugm@yahoo.co.id

11

Ulcus Ameba

Invasion of intestinal epithelial

4/3/2013dikafkugm@yahoo.co.id

4/3/2013 12

Lytic activity

Combined chemical & mechanical action:

◦ Chemotaxis

◦ Adhesion

◦ Cytolysis following contact

◦ Phagocytosis

◦ Intracellular degradation

dikafkugm@yahoo.co.id

13

Chemotaxis:

Locomotion toward target cells

Contact/ adhesion Lysis of target cells

Liberation of enzym & Toxins of amoeba

Intracellular Degradation

Amoeba :- ingest lysed cells

- engulf living cells (RBC)

Nonpathogen : lose their erythrophagocytic activity

(Entamoeba dispar similar morphology, distinc pathogenicity) 4/3

/2013dikafkugm@yahoo.co.id

14

4/3/2013

Inhibition of colonic epithelial cell functions by E. histolytica.(A) Soluble amoebic proteins activate HSF-1 in epithelial cells causing it to trimerize. Activation of HSF-1 induces expression of Hsp 27 and Hsp 72. (B) Increased levels of Hsp 72 have anti-apoptotic effects and lead to increased enterocyte survival. (C) Hsp 27 becomes phosphorylated and associates with IKK, inhibiting its activity and suppressing nuclear factor-κB activation induced by proinflammatory cytokines (IL-1, TNF) released in response to amoebic invasion.HSF = Heat shock protein transcription factor; Hsp = Heat shock protein.dikafkugm@yahoo.co.id

15

4/3/2013

Phagocytosis of host cells by E. histolitica

dikafkugm@yahoo.co.id

16

4/3/2013

Immune Response against E. histolitica

LPPG:lipopeptidophosphoglycan

dikafkugm@yahoo.co.id

17

Antibody respons

Intestinal

Circulating

Rapid

1week

IgA/ IgM/ IgG

-Diagnostic Value ELISA

-No Protective Value

4/3/2013dikafkugm@yahoo.co.id

4/3/2013 18

Antibody in Amebiasis

Ab against surface Ag

-Immobilization

Shedding of

Ag-Ab complex

Resistance to Complement lysis

Evade HumoralImmune response

Ab against lectin :

-inhibit adhesion Reduce Cytophatic Effect

-phagocytosis (+)

dikafkugm@yahoo.co.id

19

4/3/2013

Proposed model of IgA-based protection against intestinal infection of E. histolitica

dikafkugm@yahoo.co.id

4/3/2013 dikafkugm@yahoo.co.id 20

The life cycle of the malaria parasite Plasmodium falciparumand acquisition of immunity in an area of endemic transmission.

Jean Langhorne, Francis M Ndungu, Anne-Marit Sponaas & Kevin Marsh

Nature Immunology 9, 725 - 732 (2008) doi:10.1038/ni.f.205

4/3/2013 21dikafkugm@yahoo.co.id

Ab

Ab

Ab

MALARIA

Change over time of various indices of malaria in a population living in an endemic area of P. falciparumtransmission: asymptomatic infection (pink), mild disease (febrile episodes caused by malaria; blue) and severe or life-threatening disease (green). The data are normalized and are presented as the percent of maximum cases for each population index.

4/3/2013 22dikafkugm@yahoo.co.id

Clinical manifestation of malaria in relation to host immunity in endemic area

Linking innate and adaptive immunity to blood-stage

malaria.

4/3/2013 23dikafkugm@yahoo.co.id

Host immune responses against Plasmodium

4/3/2013 24dikafkugm@yahoo.co.id

Type of vaccines could be used in each specific stage of the parasite's life cycle.

4/3/2013 25dikafkugm@yahoo.co.id

Vaccine against malaria

4/3/2013 dikafkugm@yahoo.co.id 26

4/3/2013 dikafkugm@yahoo.co.id 27

Sporozoite

4/3/2013 dikafkugm@yahoo.co.id 28

ROLE OF NEUTROPHIL IN EARLY DEFENDS AGAINST T. GONDII

4/3/2013 dikafkugm@yahoo.co.id 29

BRADIZOITE FORMATION

Immunocompetent host : CMI cyst

formation

Slow rate bradiz tachiz control by

RNI

Protozoa

Helminth

Arthropod

4/3/2013 30dikafkugm@yahoo.co.id

To combat intestinal worms, mammals rely on adaptive immune responses mediated by T cells. However, it seems that, initially, innate immune cells mimic T-cell activity, while T cells get ready for action.

4/3/2013 31dikafkugm@yahoo.co.id

Immune Response againstIntestinal Nematode

4/3/2013 dikafkugm@yahoo.co.id 32

The intestinal epithelium: sensors to effectors in nematode infectionD Artis and R K Grencis

TLSP: Tymic Stromal Prot. Mucosal Immunology (2008) 1, 252–264; doi:10.1038/mi.2008.2

4/3/2013 dikafkugm@yahoo.co.id 33

parasite-specific CD4 T-cell responses elicit nonspecific "modular" type-2 responses

34

Intestinal Helminths provoke strong TH2-mediated immune responses

4/3/2013 dikafkugm@yahoo.co.id

35

Eosinophils use FcgR1 Receptor to mediate to kill helminth

4/3/2013 dikafkugm@yahoo.co.id

Antibody-coated target cells (i.e: worm) can be killed by NK cells in Antibody Dependent cell-mediated Cytotoxicity (ADCC)

4/3/2013 36dikafkugm@yahoo.co.id

Protozoa

Helminth

Arthropod

4/3/2013 37dikafkugm@yahoo.co.id

Venomous Arthropods

4/3/2013 38dikafkugm@yahoo.co.id

Hypersensitivity reactions are mediated by immunological mechanism that cause tissue damage

4/3/2013 39dikafkugm@yahoo.co.id

Arthropod’s Venom:

Mast-cell activation has different effects on different tissues

4/3/2013 40dikafkugm@yahoo.co.id

Antihistamines block Histamine-Receptors from joining with Histamine

4/3/2013 41dikafkugm@yahoo.co.id

4/3/2013 42dikafkugm@yahoo.co.id