Question

Severe combined immunodeficiency disease (SCID) is characterized by the complete lack of an immune system. Strains of mice have been developed that have SCID. When SCID mice that carry genetic predisposition to prion diseases are infected with \(\operatorname{Pr} \mathrm{P}^{\mathrm{sc}},\) they do not develop prion diseases. How do these facts relate to the transmission of prion diseases?

Short answer

An intact immune system appears essential for the transmission of prion diseases.

Step-by-step solution

Understand SCID and Prion Diseases

SCID, or severe combined immunodeficiency disease, is a condition where the immune system is completely lacking. Prion diseases are caused by misfolded proteins called prions that lead to brain damage.

Identify the Relationship in SCID Mice

SCID mice that genetically have a predisposition to prion diseases do not develop them when infected with PrP^sc. This suggests an essential role of the immune system in the development of prion diseases.

Analyze the Role of the Immune System

Since SCID mice lack an immune system and do not develop prion diseases, we can infer that a functional immune system may play a role in the transmission or development of prion diseases.

Draw a Conclusion

The lack of prion disease development in SCID mice upon infection indicates that an intact immune system might contribute to the transmission and manifestation of prion diseases.

Key concepts

Severe Combined Immunodeficiency Disease (SCID)

SCID, or Severe Combined Immunodeficiency Disease, is a serious condition characterized by a complete lack of an effective immune system. This means that individuals with SCID have a severely compromised ability to fight off infections.
SCID affects both T cells and B cells, which are crucial components of the adaptive immune system. Without these cells, the body cannot mount a proper immune response against pathogens.
Patients with SCID are highly susceptible to infections that would usually be easily controlled by a healthy immune system. Treatments often include bone marrow transplants to introduce functional immune cells into the patient’s body.

Prion Transmission

Prions are infectious agents composed entirely of a misfolded protein called PrP^sc. Unlike bacteria or viruses, prions do not contain genetic material.
Transmission of prions can occur through ingestion, contaminated surgical instruments, or blood transfusions. Once in the body, prions induce normal proteins (PrP^c) to misfold into the prion form (PrP^sc), leading to a chain reaction.
Prion diseases, such as Creutzfeldt-Jakob Disease and Mad Cow Disease, result from this accumulation of misfolded proteins, causing brain damage and, ultimately, death.

Immune System Role

The immune system plays a vital role in defending the body against pathogens like bacteria and viruses. Surprisingly, it seems to also play a role in the development of prion diseases.
In the case of SCID mice, which lack a functional immune system, these mice do not develop prion diseases even when infected with PrP^sc. This suggests that certain components of the immune system may facilitate the disease's progression.
It’s hypothesized that immune cells might help transport prions to the brain or other vital organs, where they cause damage. The exact mechanisms are still under investigation, but it’s clear that the immune system isn’t just a passive bystander in prion infections.

PrP^sc Prion Protein

PrP^sc is the abnormal, misfolded form of the cellular prion protein, PrP^c. The transformation from PrP^c to PrP^sc involves a change in the protein’s conformation, making it resistant to proteases, enzymes that normally break down proteins.
This misfolded protein is infectious and can induce other normal prion proteins to adopt the same faulty structure. The accumulation of PrP^sc in the brain leads to the development of prion diseases, characterized by neurodegeneration and spongiform changes in brain tissue.
Understanding the structure and function of PrP^sc is crucial for developing therapies that can block its formation or promote its clearance from the body.

Genetic Predisposition to Prion Diseases

Not everyone is equally susceptible to prion diseases. Genetic factors can increase an individual’s risk.
For example, mutations in the PRNP gene, which codes for the normal prion protein (PrP^c), can make the protein more likely to convert into the harmful PrP^sc form. This genetic predisposition means that these individuals are more susceptible to developing prion diseases.
In SCID mice with such genetic predispositions, the interesting finding is that the absence of an immune system prevents the onset of prion diseases, even though they have the genetic predisposition. This highlights the complex interplay between genetic factors and the immune system in prion disease progression.