Parasitology-4 Flashcards
What are the common themes of infection and immunity in extracellular parasites?
active shedding of antigens
active secretion of hydrolytic enzymes, Camouflage through binding to abundant host protein
body enlargement
How does active shedding of antigens allow parasitic infection and evasion of the immune system?
as there is an immunodominant antigen with rhomboid proteins as surface proteases that cut off and release surface antigens and immune ligands
What purpose does the active secretion of hydrolytic enzymes achieve for the parasite?
Some of the proteases have high affinity for immune effector proteins
Some proteases and glycosidases allow invasion and migration of the parasite
Proteases are involved in excystation, moulting and nutrient acquisition
How does S. mansoni survive to cause long term infection in the host?
While most parasites are killed during the invasion process however those that survive are very successful as they recruit host proteins to avoid immune system recognition allowing them to reach the liver and develop into adults
How does entamoeba histolytica ause long term infections?
It is a professional antigen shedder as there is an abundant surface lechtin (Gal/Gal/GalNAc) binds to mucin and other host glycosylated cell surface proteins this protein promotes antigen shedding by binding to cytoskeletal elements to move antigens to the posterior part ‘uroid’ which will be released by rhomboids
How do intracellular parasites avoid phagocytosis?
In order for the phagosome to fully mature it must fuse to a lysosome. This is the first point where intracellular parasites may interfere with the host reponse
How do trypanosomes or kinetoplastids avoid phagocytosis?
They have a dense layer of lipophosphoglycans resulting in inhibition of lysosomal proteolysis it also contains a detoxifying antioxidant system. It will escape the phagosome leading to the formation of a parasitophosorus vacuole
How do apicomplexan parasites avoid phagocytosis?
Instead of escaping the phagosome these parasites actively invade cells so they enter the intracellular environment without the necessity of a phagosome
What is mechanism of cell invasion through the apicomplexan parasite T. gondii?
There is initial attachment of the parasite mediated through surface antigens which provide low-affinity lateral interactions via host polysaccharides (heparan sulphate)
There is then an apical attachment through microneme proteins which are secreted and put at the tip these have adhesion domains and act synergistically.
It then extrudes its barrel like conoid like a kiss secreting micronemal (like AMA1) and rhoptry neck proteins (like RON4) these form a ring like structure known as the moving junction this migrates to the posterior of the parasite selectively removing proteins in a process which will allow it to form the parasitophosphorus vacuole
Rhoptry base proteins are secreted to the membrane of the vacuole and the host forming the parasitiophosorus vacuole
What are the commonalities of the antigens used for antigenic variation by protozoan parasites?
They are analogous but not homologous Come from a large gene family Code for surface proteins Are immunodominant They undergo mutual exclusive expression with only one variant being expressed at a time
What protozoan parasites use antigenic variation?
Plasmodium falciparum
Trypanosoma Brucei
Giardia lamblia
How is antigenic variation seen in plasmodium falciparum?
There are roughly 60 var genes which code of variants of P. Falciparum erythrocyte membrane protein 1 or PfEMP-1 as well as others such as rifin, stevor and Pfmc-2TM
Antigen variation is necessary for survival of this parasite and it is regulated through transcription factors, epigenetics and subnuclear organisation
How is antigenic variation seen in trypanosome brucei?
Thousands of variant surface glycoproteins or VSGs
Antigen variation is necessary for survival of this parasite and regulated through DNA recombination
How is antigenic variation seen in giardia lamblia?
Roughly 200 variant specific surface proteins or VSPs and mediated through epigenetics and miRNAs
What is the structure and organisation of the var genes?
The var genes are found preferentially close to the telomeres of chromosomes in 4-7 clustered foci in the nuclear periphery including those physically physically close to the centromere and surrounded telomere associated repeated elements
This facilitates recombination and genetic shuffling explaining why the three genetically distinct strains of P.Falciparum have little overlap in these genes
