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THE IMMUNE RESPONSES TO PARASITES. THE IMMUNE RESPONSES TO PARASITES. Unicellular parasites Plasmodium – malaria. Giardia lamblia - giardiasis. Life cycle of Leishmania. L. donovani – Visceral leishmaniasis (K ala azar) L. tropica – Cutaneous leishmaniasis (Oriental sore)
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THE IMMUNE RESPONSES TO PARASITES Unicellular parasites Plasmodium – malaria Giardia lamblia - giardiasis
L. donovani – Visceral leishmaniasis (Kala azar) L. tropica – Cutaneous leishmaniasis (Oriental sore) L. brasiliensis - Mucocutaneous leishmaniasis (Espundia)
THE IMMUNE RESPONSE TO THE SINGLE CELL PARAZITE LEISHMANIA Dead parazites IL-12 NO, O2-,H2O2,OH- IL-2 TNF Active radicals CLEARS THE INFECTION Th1 MACROPHAGE IFNγ IL-2 IL-10 lipophosphoglycane Leishmania major CR4 CR3 IL-4 DOES NOT CLEAR THE INFECTION Th2 MACROPHAGE
ESCAPE MECHANISMS OF UNICELLULAR PARASITES Poor antigenicity Variations in surface structure – gene conversion Alternating expression Trypanosoma Lysis of phagosome mebrane Complement (DAF) like structures Trypanosoma cruzi Inhibition of phagosome and lysosome fusion Toxoplasma
Multicellular parasites Helminths Tape worm Diphyllobothrium latum 9 m in length, lives in small intestine B12 deficiency (magaloblastic anaemia) Trichinella spiralis „pork worm”
Life cycle of Schistosoma Schistosoma mansoniDelayed Type Hypersensitivity - DTH Fibrosis around the eggs in the liver Chronic inflammation – Fibrotic connective tissue Inhibits the venous circulation of the liver
THE IMMUNE RESPONSE TO MULTICELLULAR WORMS Can not be ingested by phagocytes Plasma cell IgE BLOOD Mast cell IL-3 IL-4 mediators Th2 Permeability Eosinophil B B IgE IL-4, IL-5 Neutrophil IgG Th2 Monocyte C3a, C5a LYMPH NODE Schistosoma mansoni Activated eosinophils bind to IgE-coated parasites via the low affinity FcεRII and release their toxic contents onto the worm Other effector cells bind to IgG-coated parasites
IgE – MEDIATED CELLULAR CYTOTOXICITY Death of worm Shistosoma IgE FcεRI Granules Eosinophil granulocyte
DEFENSE MECHANISMS AGAINST HELMINTHS HOST ENVIRONMENT is accepted, resistant to complement and phagocytes SIZE – no phagocytosis RESISTANT – to reactive radicals and enzymes of macrophages and neutrophils • IgE – mediated protection • IgE-mediated antibody dependent cellular cytotoxicity ADCC • EFFECTOR CELLS:mast cells, basophils, and eosinophils • inflammatory mediators • vasodilation recruitment of inflammatory cells fluid outflow • smooth muscle cell contraction mechanical removal Schistosoma mansoniDelayed Type Hypersensitivity - DTH Fibrosis around the eggs in the liver Chronic inflammation – Fibrotic connective tissue Inhibits the venous circulation of the liver