Hello Merry, Prion disease is first of all a Protein misfolding disease which comes under a broad category of neurodegenerative disorders - meaning the structure of the Prion protein (PrP) is altered to (PrPSc) form. This altered PrPSc form will auto-infect normal cellular PrP forms and they join together to form a fibrillar structures. Now, when their stuctural form changes they can't execute the action which they're set out to do. These PrPSc-PrPSc fibrils become elongated starting to disrupt normal cell's activity and they start getting out of the cell. Other loose or uncoupled PrPSc forms escape out through vesicles into the next adjoining cell. This is how the pathogenesis of the prion is mediated. Now the strangest feature of the Prion disease is that it is not attacked by immune cells rather seems to aid their infection. Well basically the infectious form is very stable and is found to be not affected even by high salts and esters. Also in some ways the proteosomes are rendered ineffective to the PrPSc.

There is research going on in this field to identify humoral and cellular immune cells which seem to aid the propagation. The proposed hypothesis is that the Dendrite cells are invaded by the Prions which then start infecting those cells and stop they antigen presenting ability.

Prions are technically "non-foreign". They are just mutated normal proteins that has catalytic capability that can cause more normal proteins to mis-fold and cumulate. Plus these chemical reactions are happening in side brain which is immune restricted organ. That's make them "untouchable". I think.

When presented by antigenpresenting cells under inflammatory conditions prion proteins (and any other protein-regardless of whether being of self or foreign origin, conformationally changed or not) will raise adaptive immune responses. Conversely, in absence of inflammation, even foreign proteins are tolerated.

Hello Merry, Prion disease is first of all a Protein misfolding disease which comes under a broad category of neurodegenerative disorders - meaning the structure of the Prion protein (PrP) is altered to (PrPSc) form. This altered PrPSc form will auto-infect normal cellular PrP forms and they join together to form a fibrillar structures. Now, when their stuctural form changes they can't execute the action which they're set out to do. These PrPSc-PrPSc fibrils become elongated starting to disrupt normal cell's activity and they start getting out of the cell. Other loose or uncoupled PrPSc forms escape out through vesicles into the next adjoining cell. This is how the pathogenesis of the prion is mediated. Now the strangest feature of the Prion disease is that it is not attacked by immune cells rather seems to aid their infection. Well basically the infectious form is very stable and is found to be not affected even by high salts and esters. Also in some ways the proteosomes are rendered ineffective to the PrPSc.

There is research going on in this field to identify humoral and cellular immune cells which seem to aid the propagation. The proposed hypothesis is that the Dendrite cells are invaded by the Prions which then start infecting those cells and stop they antigen presenting ability.

does immune system involved as one of the factor that make a "barrier species" in prion trasmission?

i mean why it could be easier for BSE transmittied in same species (longer time incubation for trasmission to other kind of species)?

Well, definitely the immune system must play a role or be a barrier in infection, but it is not sure how. As you point out the incubation period for BSEs, nvCJDs, kuru all these TSEs differ in different species. However that does not necessarily mean a immune response preventing their pathology. Different incubation times may result from the level of infections, mode of infection (oral -ingested or direct- injected), lines in which the strain of pathology developed in the main infected animal, also the pathological symptoms might differ meaning the level of lesion production may not be on the same lines as of other species.

I will tell you about another interesting hypothesis about the Prion diseases - one called 'virion hypothesis'. It states that the prion diseases are caused by some unsuspecting, unknown virus particles majorly RNA viruses, which is yet to be discovered. But till date the virion theory is not found to be established. But is quite fascinating and proves the capability to multiply and replicate the Prions and capable of transmission to another species. Which might also give a clue as to why it takes more incubation times.