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 (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 mansoni Delayed Type Hypersensitivity - DTH Fibrosis around the eggs in the liver Chronic inflammation – Fibrotic connective tissue Inhibits the venous circulation of the liver

Granuloma in the liver

Hepatosplenomegaly

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

Schistosoma lárvát támadó eozinofil sejtek

Mast cells

Eozinophils

IgE – MEDIATED CELLULAR CYTOTOXICITY Eosinophil granulocyte 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 mansoni Delayed Type Hypersensitivity - DTH Fibrosis around the eggs in the liver Chronic inflammation – Fibrotic connective tissue Inhibits the venous circulation of the liver