2. Immunity against Parasitic infection Prof. dr. Supargiyono DTM&H, PhD, SpParK. Department of Parasitology FM. UGM.

3. Parasitic infection   Parasitic infection is caused by animal parasite: – –protozoa pathogenic:   Rhizopoda – –Entamoeba histolytica, – –Entamoeba coli   Ciliata: Balantidium coli   Flagelata : – –Trichononas vaginalis – –Giardia lamblia   blood & tissue : – – Plasmodium falciparum, – –P. vivax, – –P. malariae, – – P. ovale, P. knowlessi – –Toxoplasma gondii; – –Trypanosoma (Sleeping sickness), – –Liesmania (skin lesion);etc.

4.   Helminthes : – –Nematodes (round worm):   intestinal : Ascaris lumbricoides, Oxyuris vermicularis, Trichuris trichiura, Ancylostoma duodenale & Necator americanus (Hook worm);  Soil Transmitted Helmithes (STH)   blood & tissue : Filarial worms :   Lymphatic: Wuchereria bancrofti, Brugia malayi, Brugia timori   Non-Lymphatic: Loa-loa, Onchocerca sp. – –Cestodes (tape worm): Taenia saginata, T. solium, Diphylobothrium latum, Hymenolepis nana, E. granulosus, etc. – –Trematodes (fluke):   Liver : Fasciola hepatica,   Intestinal : F. buski (intestine),   Lung : Paragonimus westermani,   Blood & Lymph : Schistosoma japonicum, S. mansoni, S. hematobium, etc.   Arthrophode (insect) : – –ectoparasite (tick, mites, louse, etc)

5.   The prevalence : – –More then 30% world population suffer parasitic infection – –More in developing countries   Most parasites : – –Go through complex life cycle   part of which in human and other vertebrate host   The other part in intermediate invertebrate host (mosquito, fish, flies, etc) Fasciolopsiasis

6. Fundamental feature of parasitic infection   Most parasite produce chronic infection   Reasons : - -in endemic area parasite persisted in favorable environment  available reservoir  produce repeated infection - -weak natural immunity - -infective stage are resistance to unfavorable environment - -parasite are able to evade specific immune responses - -many antiparasite antibodies are not- effective & toxic

7. Immunity against parasitic infections   Immunity to parasites : - -Innate/Natural resistances  general - -Acquired resistances  specific (antibody)   Most parasites (Protozoa & helminth) enter the body (GI tract, blood stream/tissue) passing Natural resistance (barrier) of the body – –well adapted to resisting natural host defence (cyst of intestinal protozoa, worm eggs, hookworm larvae etc) – –able to evade lysis by complement – –able to survive inside phagocytic cells – –integument of helminth resistant to cytosidal of neutrophylls and macrophage

8. Specific immune responses to parasites  Parasites : Varies greatly : structure & molecular constituent variety of immune responses Histamin, Proteases, Etc. Histamin, Proteases, Etc.

9. Major pattern of specific Immune Responses to parasites 1) 1) Production of specific IgE & Eosinophilia in helminthic infection Stimulation of Th2(CD4+TCell): release IL4 (interleukin 4)  elevation of serum Ig E release IL5 (interleukin 5)  eosinophilia IgE-dependent cytotoxicity by eosinophils is efective in killing some helmiths Major basic protein of eosinophil granules are toxic for helminths Stimulation of Th1 (CD4+TCell)  IFN  activation of M@  secretes NO & TNF (kill the parasites: malaria) Eosinophil MJP

10. Major pattern of specific Immune Responses to parasites (cont) 2. 2. Some parasites & their product induce granulomatous responses  fibrosis Schistosoma mansoni egs in liver induce fibrosis  disrupt venous blood flow  portal hypertension  cyrhosis Lymphatic filariasis, filarial worm in lymphatic vesel  chronic CMI  fibrosis  lymph-obstruction  severe chronic lymphedema  elephantiasis.

11. Major pattern of specific Immune Responses to parasites (cont) 3. Protozoa that replicate inside cells (intracellular parasites) stimulate specific CTLs (cytotoxic T lymphocytes) 4. Extracellular parasite antigen stimulate antibody responses (humoral immune responses) Antigen-Antibody reaction complex  deposition tissue dammage (glomerulonefritis, renal failure, etc) Attached are pathology & imunology of some parasitic diseases

12. Presentation of parasite antigen

13. Immune responsis against intracellular parasites

14. Loefler syndrome GI irritation : diarhea, naucea, vomitus, abdmnl discomfort Immunologis : elevation of IgE Eosinophillia, urticaria

15. The hook worm Skin : alergic reaction Serum : IgE & Eosinophylia

16. Trichinella spiralis

17. Taenia saginata Cystecercuc bovis

19. Eosinophills, IgE

20. Immune Response to Filaria parasite Following infections high levels of anti- parasite IgE and IgG4 are produced which is generally accompanied by eosinophilia. This is due to the preferential stimulation of T-cells which produce IL-4 and IL-5(Th-2 type). (In asymptomatic microfilaremic patien) Elephantiasis may result from killing of late stage larval antigens by IgE mediated mechanisms or by a passive reaction of naturally dying adult worms, evoking inflammatory reactions. The patients with tropical pulmonary eosinophilia (TPE) elicit a very high IgE response which is predominantly developed against microfilaria. In TPE mf are not found since the immunological hyper-responsiveness removes this stage of the parasite from circulation. tropical pulmonary eosinophilia (TPE) tropical pulmonary eosinophilia (TPE)

24. Entamoeba hystolitica

25. Clinical manifestation : due to erythrocytic stage Infected RBC adhered to endothelial cell in some organ (cytoadherent) Normal RBC adhered to infected RBC  rosetting  Sequestration Intermitten fever: due to ruspture of RBC  released toxic product Spleen : important organ of the immune system  splenomegaly & macrophage hyperplasia : hallmark of malaria Splenic macrophages full of parasitic pigments. ring P. falciparum  malignant Tertian malaria P. vivax  benign tertian malaria P. malariae -  Quartant malaria P. ovale  malaria ovale

26. References: References: 1. Abul K. Abbas, Andrew H. L., Jordan S.P. 1994. Cellular and Molecular Immunology. Second edition. W.B. SOUNDERS Co. 2. Jeffrey H.C. and Leach R.M., 1975. Atlas of Medical Helminthology and Protozoology, Second edition. Churchil Livingstone, London.