Immune Evasion

What are some examples of how parasites evade compliment-mediated innate immune responses?

• trichinella spiralis — express calreticulin on their surface and secrete it into the environment

  • protein binds one of the host compliment subunits, inhibits its function, prevents effector functions from taking place

• schistosoma mansoni — express surface SCIP—1 that binds a compliment subunit that prevents formation of the membrane attack complex

What are some species that have mechanisms to avoid destrction in host cells?

toxoplasma gondii, trypanosoma cruzi, leishmania

• all can survive low pH of macrophage phagolysosome

How does leishmania evade host immune response?

• parasite has a thick coat (LPG) which delays formation of phagolysosome and prevents NOX complex formation 

• superoxide radicals formed are borke down by parasite superoxide dismutase (SOD)

• secretes or induces macrophages to produce arginase 

  • arginase provides essential nutrient for parasite 

How do parasite interfer with intracellular signaling pathways?

(A) in phagocytes, PKC is activated in response to ligand binding —> phsophrylates (activates) NADPH oxidase —> enzyme converts O2 into superoxide radical (respiratory burst)

(B) hemosoin is a waste product of Plasmodium when parasite ingests hemoglobin in infected RBCs —> RBCs lyse —> hemozoin in released and phagocytosed —> interfer with PKC activity —> decreased superoxide production (less effective respiratory burst)

What are examples of intracellular parasites that interfere with apoptosis?

1. eimeria tenella — invade epithelial cells in intestines of chickens

• activation of host cell TF —> increases expression of protein that blocks apoptotic response

2. toxoplasma gondii — parasite stimulates up-regulation of host proteins that prevent the apoptotic response

What are examples of parasites that interfere with antigen presentation

1. toxplasma gondii — prevents parasitophorus vacuole from fusing with host cell vesicles

• stay isolated in cytoplasm of macrophages and dendritic cells

• cannot be processed, and antigens cannot be presented by MHC II

2. filarlia nematodes — produce cystatins (cysteine protease inhibitors)

• inhibit host proteases from processing parasite antigens for presentation by MHC II

3. schistosoma mansoni — secretes w-1, which contains mannose residues in carb portion of the molecules

• w-1 bind mannose receptors on the surface of dendritic cells —> taken up by the cell —> degrades host mRNA —> inhibition of translation (including mRNA encoding MHC II)

How do African trpanosomes avoid immune responses?

• change their surface antigens regularly

  • new antibodies must be generated for each distinct VSG protein