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47 Cards in this Set
- Front
- Back
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What are the major evasion mechanisms of the protozoans?
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Escape from mac phagolysosome
Resistance to humoral and/or cellular immune response Ag variation (T. brucei) Host cell signalling pathway alteration and inhibition of mac fct (Leishmania) Modulation of host cell fcts responsible for pathology development (malaria) |
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How does T. gondii evade the phagosome?
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Live parasite in the phagosome inhibits its fusion with the lysosome
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How does T. cruzi evade the phagosome?
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Parasite survives entry and divides freely in the cytoplasm
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Describe how the Leishmania evades the phagosome
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Parasite resists lysosome enzyme and divide in the vacuole
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Which parasites block the fusion of the phagosome with the lysosome?
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T. gondii
Leishmania |
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Which parasite allows fusion of the lysosome and phagosome?
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T. cruzi
Allows fusion, but will escape and replicate in the cytoplasm |
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What kind of cells can T. gondii infect?
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Phagocytic and non-phagocytic
Hard to contorl infection in non-phagocytic cells |
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Avoidance of Humoral and CMI response by Parasite:
Importance of the Ab Response |
T. brucei (free in the blood): ++++
Plasmodium (inside RBC): +++ T. cruzi (inside mac): ++ Leishmania (inside mac): + |
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Avoidance of humoral and CMI responses by parasite:
Ab mechanism |
T. brucei: Lysis with C' which opsonizes for phagocytosis
Plasmodium: Blocks invasion, opsonizes for phagocytosis T. cruzi: Limits spread in acute infection Leish: Limits spread |
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Avoidance of humoral and CMI responses by parasite:
Evasion mechanism |
T. brucei: Ag variation
Plasm: Intracellular habitat T. cruzi: Intracellular habitat Leish: Intracellular habitat |
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How important is CMI in these parasites?
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T.brucei: No CMI
Plasmodium: A little important, activate Macs T. cruzi: CMI activation very important (in chronic stage), uses mac activation anf killing by O2 metabolites Leish: CMI very important, activates macs by lymphokines and killing by O2 metabolites |
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What is the geographical distribution of T. brucei?
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Africa/South Africa
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Describe the relationship between T. brucei's Ag variation and the humoral response?
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The parasite will make A Ag, so the body producesAb vs it, so the parasite load decreases
Then, parasite changes its surface Ag and new Ab ned to be produced to agains lower parasitemia Parasite continues to change its surface Ag |
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What vector carries T. brucei?
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Tsetse fly
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What immune response controls a Leish infection?
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CMI only!
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How does Leish modulate the host cell fct?
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Alters signalling paths and subverts host IR
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How does Plasmodium (malaria) modulate host cell fct?
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Modulatesthrough pathology development
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How does the Leish gett into macs?
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Has different ligands that interact with the receptors on the macs
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How does Leish escape?
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Use gp63: metallic protease
This protease can get through lipid rafts, doesn't require a receptor |
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What does Leish induce?
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Induces phosphatase SHP-1
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What does Leish do by inducing SHP-1?
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Inactivates many signalling paths (including Jak-Stat path)
.: many macs fct couldn't be induced -Induce proteasome --> Control NF-kB by altering STAT-1 -Based on PKC, P other ptns (how parasite avoids induction or O2 radicals) |
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What happens to STAT after IFN-y is released?
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STAT-1 goes to the nucleus
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What happens to STAT after L.donovanii infection?
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L. d can cleave STAT and it won't be able to go to the nucleus
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What do most leish species do to inhibit different pathways?
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Decrease P by increasing Phosphatases
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Which Leish cannot activate Ptn tyr phosphatases?
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L. tarentolae
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What is required to activate host ptn tyrosine phosphatases?
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GP63
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What happens if GP63 is removed from L. major?
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It can't KO tyr phosphatases anymore
GP63 is responsible forr phosphatase activation |
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What happens once GP63 enters the mac through the lipid raft?
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Activates tyr phosphatases, inactivates Jak-Stat
SH-1 interacts with IRAK-1 .:Leish blocks inflammation response by blocking P and increasind deP SH-1 interacts with IRAK-1 and inhibits IL-17, NO, TNF-a --> Freezes the system |
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What do peroxovanadium compounds do?
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Favor a Th1 response
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What is required to contorl Leish infection?
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Control the tyr phosphatases
-->If you treat mice with bpV ->Control inflam, swelling and stop lesions from forming |
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What does malaria do?
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Causes a moer pro-inflammatory response
Induces cytokine storm |
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Where is malaria situated?
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Mostly in Africa
Also in South America |
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Describe the life cycle of malaria
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Parasite injected into bloodstream
Get into Liver Go to RBCs RBCs burst Merezoites and metabolic waste (including hemozoin) are released |
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Which malaria parasite has a GPI?
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P. falciparum
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What does the GPI moiety do?
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Causes ondulation of TNF-a, IL-1B
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What does the GPI lead to?
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Cytokine release
Transient pyrexia Hypoglycemia |
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What cytokines does malaria induce?
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TNF-a, IL-1/6
MIP-1B/a, IL-8 ROS NO |
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What cytokines does hemozoin induce?
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TNF-a, IL-1b in vitro
MIP-1a, MIP-1b in vitro ROS Thermoregulation Anti-HZ Ab |
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What does Hz have?
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In vivo: pro-inflammatory properties
Intracelular signalling mechanism |
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What does Hz do?
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eats Hb, diigests it and uses its aa to help parasite
Heme is left over It is too toxic for humans and parasite By heme polymerization, get heme crystals |
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What makes P. falciparum so deadly?
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Might be Hemozoin
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What happens a few days after a malaria fever?
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Dec PKC
Dec MHC II Dec oxidative stress |
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What does hemozoin induce?
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Inc lipid peroxidation, MIP-1a/B, cytokines
Dec: phagocytosis, oxidative stress, PKC, MHC II |
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What happens when malaria induces NO and RNI?
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Increased Microbicidal activity (good to fight off the malaria)
Causes tissue damage, immunosuppression, celebral malaria (bad things for you) |
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What intracellular signals does Hz trigger?
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Mac activation (Danger signal)
Neutrophils, DCs |
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What affect does Hz have on luekocytosis and inflam mediator?
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Causes increased leukocytosis and increased inflam mediator overproduction
-->These cause tissue damage, microvascular flow disturbance, organ-ass't pathology |
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What are the clinical manifestations of malaria?
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Organ sprcific effects:
Hz accumulation in the brain Microglial: inc S100a8/9, TNF-a, MCP-1, ECM development: Neutrophils, CCR5--> induce megatropoblasts: favors HIV replication Placental malaria: Ince monocytes, MIP-1a, MCP-1, correlation TNF-a, IL-8, HZ |
