04/18/2023 Even Semester 2014

BLOCK MPT 2014

IMMUNE RESPONSE IN PARASITIC DISEASES

non-genetic

Innate immune system

genetic

IMMUNE SYSTEM

humoral

Adaptive immune system

celluler

04/18/2023 Even Semester 2014

PARASITE

Multicellular : Helminths

Unicellular : Protozoa

Intracellular : Plasmodium

Extracellular: Entamoeba,Giardia lamblia

Large size : antigens >>Multi stage : variation of antigens

PARASITE INFECTION:

• complex multistage life cycles & 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.

04/18/2023 Even Semester 2014

• The immune response that develops often proceeds to cause pathologic changes.

04/18/2023 Even Semester 2014

PARASITE SURVIVAL STRATEGIES

• Locations: • live in a cyst: Toxoplasma and larva

T.spiralis live in the muscle cyst • Intracellular: Plasmodium• Migration : Hookworm move to escape the

reaction of inflammation

04/18/2023 Even Semester 2014

HOOKWORM INFECTION

04/18/2023 Even Semester 2014

PARASITE SURVIVAL STRATEGIES

• Antigenic variation

• Mimicry ( mimicking host antigens)

• Produced soluble antigen

• Supression – regulatory environment: Produced

immunomodulator toxins: Leishmania

produce anti-oxidase inhibit IL-12

by the infected macrophages

04/18/2023 Even Semester 2014

• Antigenic variation:• VSG (variant surface glycoprotein ) is a

surface molecules which cover the entire surface of Trypanosoma gambiense / T. rhodesiense (African Sleeping sickness)

MICHAEL F. GOODNATURE 400, 25-26(1 JULY 1999)

04/18/2023 Even Semester 2014

ACUTE AND CHRONIC CONDITIONS

RESPONSE TO HELMINTHS

• Multicellular : couldn’t be phagocyte

• exist in different stages : eggs, larvae, adult

• Variation of surface antigens • Independently triggered host immune response

Difficult to

eliminate

• 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

RESPONSE TO HELMINTHS

04/18/2023 Even Semester 2014

RESPONSE TO HELMINTHS

• 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)

04/18/2023 Even Semester 2014

SCHISTOSOMIASIS:STIMULATION OF TH1, EGGS : STIMULATION OF TH2

release omega 1 CD4 Th2 cell ,IL-13,Macrophage, eosinophil

04/18/2023 Even Semester 2014

OUT COMES ASSOCIATED WITH SPECIFIC IMMUNE RESPONSE TO FILARIA

• The presence of Wolbachia (endo symbiotic bacteria) induce Th1 and Th2 cell

• Wolbachia induced pro-inflamary cytokine IL-6 , TNF, macrophage and chemotactic activity by neutrophils

04/18/2023 Even Semester 2014

OUT COMES ASSOCIATED WITH SPECIFIC IMMUNE RESPONSE TO FILARIA

04/18/2023 Even Semester 2014

IMMUNITY TO PROTOZOA

• immunity against intracellular protozoa is principally mediated by Th1-triggered macrophages

04/18/2023 Even Semester 2014

IN TOXOPLASMOSIS:

IMMUNITY TO MALARIA: INNATE IMMUNITY

• Genetic (associated with human red blood cells ):• Persons who are negative for the Duffy

blood group are resistant to infection by P. vivax.

• People with thalassemia heterozygote relatively resistance to malaria infection ((50% reduction in infection),

INNATE IMMUNITY TO MALARIA:( GENETIC)

• sickle cell trait (heterozygotes for the abnormal hemoglobin gene HbS) are relatively protected against P. falciparum (90% protection) and confer protection against severe malaria and related mortality

• G6PD deficiency, are thought to provide protection from malaria disease (50% protection).

INNATE IMMUNITY TO MALARIA:( GENETIC)

• People with Southeast Asian Ovalocytosis (SAO) relatively resistant to P. falciparum and P. vivax infections.

04/18/2023 Even Semester 2014

04/18/2023 Even Semester 2014

ADAPTIVE IMMUNITY

• Plasmodium falciparum variant surface antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against falciparum malaria.

04/18/2023 Even Semester 2014

04/18/2023 Even Semester 2014

04/18/2023 Even Semester 2014

IMMUNE RESPONSE :

• Not always protected• Reinfection in Plasmodium, Ascaris infection

• Not always beneficiary:• Immunopathology Response

• Serological test for diagnosis • Make vaccines: Malaria

• Ag-Ab immune complex in malaria : glomerulonephritis

• P. falciparum infection: parasitized red blood cells adhere to the cerebral capillary (Cerebral malaria)

IMMUNE RESPONSE (CONT’D)

• 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

• Response granulomatous to eggs of Schistosoma in liver

cirrhosis

04/18/2023 Even Semester 2014

MALARIA VACCINE

• CSP(circumsporozoit protein)• LSA (liver stage antigen)

•Pfs 28 & Pfs 25

•MSP (merozoite surface protein)•RESA (ring infected surface antigen)