Immuno-Parasitolgy: Immune Response and Immuno-Diagnosis in Parasitic Diseases

IMMUNO-PARASITOLGY
Immune Response and Immuno-diagnosis In Parasitic Diseases

Powerpoint Templates Page 1
non-genetic
Innate immune system

IMMUNE SYSTEM Adaptive immune system
Powerpoint Templates
genetic
humoral
celluler
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Parasite :
Multicellular : Helminths Unicellular : Protozoa
Intracellular : Plasmodium
Extracellular : Entamoeba
Large size : antigens >> Multi stage : variation of antigens
Parasite infection:
Have complex multistage life cycles that involve several hosts. Route of infection can differ from oral to penetrate through the skin directly (hookworm) or by infectious bites of vector ( malaria) Many parasites are long-lived and cause chronic infections.
Parasite infection(contd)
chronic parasite-infections are common owing to weak innate immunity and parasite capacity to evade the immune response The immune response that develops often proceeds to cause pathologic changes.
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Parasite survival Strategies

Locations:
Paragonimus live in a cyst in the lung , Toxoplasma and larva T.spiralis live in the muscle cyst, Plasmodium live inside the red blood cell
Migration : Hookworn (A. duodenale ) move to escape the reaction of inflammation
Parasite survival (contd)

Antigenic variation: VSG (variant surface glycoprotein ) is a surface molecules which cover the entire surface of Trypanosoma gambiense / T. rhodesiense (African Sleeping sickness)
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Parasite survival (contd)

Mimicry ( mimicking host antigens) , ex: Schistosoma Produced soluble antigen : depressed the immune response (ex: lymphocytotoxic fc ) Produced immunomodulator toxins: Leishmania produce anti-oxidase inhibit IL-12 by the infected macrophages
Target organ of helminths infection
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Response to Helminths
Multicellular: couldnt be phagocyte exist in different stages : eggs, larvae, adult Variation of surface antigens Independently triggered host immune response Difficult to eliminate
Response to helminths(contd) Induced both humoral and cellular response immunity against helminthic infections is mediated by Th2 cells, mast cells / basophils Effector mechanism are eosinophil and produced Ig E
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Secreted immunomodulators : e.g. cysteine protease inhibitors (cystatins)

Inhibit antigen processing and presentation reduce T cell responses
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Response to the intestinal nematodes

Inflammation and increase intestinal motility is CD4 T-cell subset Th2 dependent
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Exception :
In schistosomiasis and filariasis , induced Th1 and Th2 Schstosomiasis : in early infection, dominant induced Th1. After the worm laying eggs : induced Th2 cell (antigen release is omega 1 , a glycoprotein + ribonucleic acid activity)
Formation of granuloma:
Eggs that trapped in the tissue
release omega 1
CD4 Th2 cell ,IL-13, Macrophage, eosinophil
granuloma
fibrosis of the liver

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Filariasis :
The presence of Wolbachia (endo symbiotic bacteria) induce Th1 and Th2 cell Wolbachia induced pro-inflamary cytokine IL-6 , TNF, macrophage and chemotactic activity bay neutrophils
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Out comes associated with specific immune response to Filaria
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Immunity to Protozoa
immunity against intracellular protozoa is principally mediated by Th1-triggered macrophages
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Innate immunity in Malaria

Genetic :
Play role in early infection:
malaria
RBC membrane disorder: Antigen Duffy : a receptor for P. vivax. People with Ag Duffy (-) more resistant P. vivax infection
Innate immunity
(contd)
falciparum more resistant to P. falciparum infection Ovalocytocis

Disorder of band 3 protein, more resistant to P. vivax, P. malariae and P.
Glycophorine A: receptor for P.
falciparum
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Erythrocyte disorder
G-6-PD deficiency : patients more resistant to P. falciparum Haemoglobinopathy: condition of RBC influence the life of Plasmodium:
Sickle cell anemia Thalasemia Hb -F; Hb- C; Hb-D; Hb-E
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non genetic
Hormone: pregnant woman easier to have complicated malaria
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Immunity to Plasmodium
The Plasmodium exists in humans in :
extracellular forms: sporozoites and merozoites, intracellular stages in hepatocytes and erythrocytes. Its stimulates CD4 and CD8 T cells, gamma-delta T cells, macrophages, natural killer (NK) cells, and B cells make antibodies against epitopes on the surface of the sporozoite,
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Ab helping macrophage to phagocyte Trypanosome
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In toxoplasmosis
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Response to Intestinal protozoa

Gut Associated Lymphoid tissue (GALT) Mucosal lymphoid follicles Immunological active cell in the lamina propria The protozoa stimulate inflammation:
Proliferation, crypt >>, atrophy of the villous Malabsorption syndrome Powerpoint Templates Hypermotility Page 31
Response to intestinal protozoa infection

Activation of Intraepithelial lymphocyte, especially CD8+ T cell Function:
To produce cytokine ( IFN and IL10) Cytotoxicity process Apoptosis and cell regeneration
Immune response :
Not always protected
Reinfection in Plasmodium, Ascaris infection
Not always beneficiary: Immunopathology Response Allergic reaction: anaphylactic shock in hydatidosis
Syndroma Loeffler
Ag-Ab immune complex in malaria : glomerulonephritis P. falciparum infection: parasitized red blood cells adhere to the cerebral capillary (Cerebral malaria)
Immune response (contd)

Chronic Amebiasis : formation of
granuloma surrounding the amebic ulcer (ameboma / amebic granuloma)
Cardiomyopathy in Chagas disease ( Trypanosoma cruzi infection) : autoimmune reaction to the nerve ganglion
Onchocercosis : Auto immune response to microfilaria of Onchocerva volvulus produce blindness
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The Advantage of Immune response :

I. Immuno-diagnosis (sero-diagnosis) Based on antigen-antibody reaction Antibody / antigen detection When do we need ?? Parasite difficult to find Pre-patent and chronic phase Light infection (number of parasite <<) Powerpoint Templates Page 37
II. Make vaccines

An ideal malaria vaccine : safe, cheap, easy to manufacture, easy to administer and confer life-long immunity against the disease Three main types of vaccines, are being developed:
1. A pre-erythrocytic / antisporozoite :
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1. A pre-erythrocytic / antisporozoite :
would prevent invasion of hepatocytes by sporozoites and/or prevent liver-stage parasites from developing to maturity, e.g.: o CSP ( circum sporozoite protein)
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2. Againts asexual blood stage
to induce Ab that neutralize/ destroy the merozoites and infected RBC, and block cytoadherence, Proteins identified : MSP 1 (merozoit surface protein), MSP 3
Vaccines against asexual blood (contd)

o apical merozoite surface antigen 1 (AMA-1), o the 175 kDa erythrocyte binding antigen (EBA175) o and rhoptry- associated protein 1 (RAP-1), RAP-2 o RESA (ring infected erythrocyte surface antigen)
3. Blocking transmission
inducing Ab that inactivate gametocytes and interfere with fertilization would prevent transmission of the disease.
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Immunocompromised host
some diseases can be dangerous and fatal Helminths :
Strongyloides stercoralis Cysticercosis
Protozoa:
Toxoplasma gondii Cryptosporidiosis Cyclospora

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IMMUNO-PARASITOLGY

Immune Response and Immuno-diagnosis In Parasitic Diseases

Innate immune system

Parasite survival Strategies

Parasite survival (contd)

Parasite survival (contd)

Target organ of helminths infection

Secreted immunomodulators : e.g. cysteine protease inhibitors (cystatins)

Response to the intestinal nematodes

fibrosis of the liver

Out comes associated with specific immune response to Filaria

Innate immunity in Malaria

falciparum more resistant to P. falciparum infection Ovalocytocis

Glycophorine A: receptor for P.

Ab helping macrophage to phagocyte Trypanosome

Response to Intestinal protozoa

Response to intestinal protozoa infection

Immune response (contd)

Onchocercosis : Auto immune response to microfilaria of Onchocerva volvulus produce blindness

The Advantage of Immune response :

II. Make vaccines

2. Againts asexual blood stage

Vaccines against asexual blood (contd)

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