THE IMMUNE RESPONSE TO PARASITES

Pulendran B, Artis D (2012) Science 337:431-435.

Multicellular parasite infections trigger Th2 type adaptive immune response

The elicited Th2 response leads to the production of IgE/IgG antibodies

The role ofdendritic cellsis critical in the initiation phase of anti-parasiticTh2 responses.

The main sourcesof the Th2 polarizingcytokine IL-4:

1. DCs

2. Basophils

3. Eosinophils

4. NKT cells

Gause WC et al. (2013)Nat Rev Immunol 13:607-614.

Unicellular protozoa

Plasmodium (malaria)

Leishmania

Toxoplasma

THE IMMUNE RESPONSE TO PARASITES

The life cycle of Plasmodium

Inoue SI et al. (2013) Front Immunol 4:258.

Inoue SI et al. (2013) Front Immunol 4:258.

Main components of the immune response to Plasmodium

macrophages„clearance”role of the spleen!

Dead parazitesIL-12

TNFIL-2

Th1

Th2

IL-2 IL-10

IL-4

IFNγ

Leishmania major

MACROPHAGE

NO, O2-,H2O2,OH-

CR3CR4

lipophosphoglycane

CLEARS THE INFECTION

DOES NOT CLEAR THE INFECTION

MACROPHAGE

Active radicals

Immune response to the single cell parasite Leishmania

credit: www.ppdictionary.com/parasites/gondii_t.jpg

credit: DJP Feruson/University of Oxford

Toxoplasma gondii, the „brain-hacker” parasite

Global prevalence: 30%(seropositivity in human populations)

Rarely causes clinical symptoms inhealthy adults; the endangered membersof the population are children, elderly people,Immunosuppressed individuals, etc.

The genome of T. gondii encodes two aromatic hydroxylases that allow the parasite to synthesize dopamine. This may influence the behavior ofseropositive indviduals (e.g. increased risk-taking).Recently, T. gondii infections have beencorrelated with many neuropsychiatric diseases:

- schizophrenia (38 large cohort studies, strong positive correlation);- epilepsy;- OCD (7 large cohort studies, positive correlation);- Bipolar disorder (the correlation has been unclear);

Hunter CA & Sibley LD (2012) Nat Rev Microbiol 10:766-778.

Sauer A et al. (2013) Int J Parasitol 43:721-728.

Main characteristics of the immune response to Toxoplasma:

Multicellular parasites

Helminths

Diphyllobothrium latum

Trichinella spiralis

ECFNCF

C'

THE IMMUNE RESPONSE TO MULTICELLULAR WORMS

Can not be ingested by phagocytes

C3a, C5a Monocyte

Neutrophil

Eosinophil

Mast cellIL-3IL-4

Plasma cell IgE

mediators

B

B

Th2

Th2

IL-4, IL-5

LYMPH NODE

IgE IgG

BLOOD

Schistosoma mansoniActivated eosinophils bind to IgE-coated parasites via the high affinity FcεRII

and release their toxic contents onto the wormOther effector cells bind to IgG-coated parasites

Permeability

Mast cells

Eosinophil granulocytes

IgE – MEDIATED CELLULAR CYTOTOXICITY (ADCC)

Shistosoma

Eosinophil granulocyte

IgE

FcεRI

Death of worm

Granules

DEFENSE MECHANISMS AGAINST HELMINTHS

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

HOST ENVIRONMENT is accepted, resistant to complement and phagocytes

BIG – no phagocytosis

RESISTANT – to reactive radicals and enzymes of macrophages and

neutrophils

Schistosoma mansoni Delayed Type Hypersensitivity - DTHFibrosis around the eggs in the liver Chronic inflammation – Fibrotic connective tissueInhibits the venous circulation of the liver

ESCAPE MECHANISMS OF PARASITES

Poor antigenicity

Variations in surface structure – gene conversion

Alternating expression

Trypanosoma

Privileged sites isolated from the immune system (cyst)

Intracellular Leishmania, Toxoplasma

Inhibition of phagosome and lysosome fusion

Toxoplasma

Antigen masking by bound self proteins

Complement (DAF) like structures