Week 4: Lecture 3

What is the goal of achieving immune tolerance in transplant patients?

To allow the transplanted organ/tissue to be recognized as self, enabling patients to stop taking immunosuppressant drugs.

Why do transplant patients typically require lifelong immunosuppressant drugs?

To prevent rejection of the transplanted organ by the immune system.

What are some adverse effects associated with lifelong immunosuppression?

Kidney damage and liver damage.

What is severe T cell depletion in the context of inducing tolerance?

Wiping out the recipient's immune system and then reconstituting it to view donor tissue as self.

What is bone marrow chimerism?

Introducing donor bone marrow to create a mixed immune system that may accept the transplant.

Which types of T cells are utilized to help achieve immune tolerance?

Regulatory T cells.

What is the role of the co-stimulatory molecule B7 in T cell activation?

It engages with CD28 on T cells to provide a critical signal for T cell activation.

What happens if the co-stimulatory signal is not provided during T cell activation?

T cell activation does not occur.

How does CTLA-4 contribute to the regulation of T cells?

CTLA-4 inhibits T cell proliferation by binding to B7.

What is the mechanism of action for drugs like Abatacept and Belatacept?

They block the B7 molecule on APCs, preventing its interaction with CD28 on T cells.

How do Abatacept and Belatacept mimic CTLA-4?

They are fusion proteins that consist of the antibody FC region fused to the extracellular regions of CTLA-4.

In the context of kidney transplantation, how does Belatacept compare to cyclosporine?

Belatacept is superior, showing better kidney function over time as measured by glomerular filtration rate.

What was the limitation of Belatacept, despite its efficacy?

It does not induce immune tolerance.

What is xenotransplantation?

Transplantation of organs from genetically modified animals, such as pigs, to humans.

What modification is made to pigs in xenotransplantation?

Pigs are genetically modified to delete highly immune-activating antigens.

Why is genetically modified pig organ transplantation of interest?

It can offer a solution to the shortage of available human organs.

What was a significant outcome of the first surgery using modified pig hearts?

The patient survived for a limited period but was considered a success.

What potential future benefits does xenotransplantation hold?

A more manageable supply of organs, reducing waiting lists for human organs.

What are the current limitations of immunosuppressant therapy?

Lifelong use, significant adverse effects, and a lack of true immune tolerance.

What are some key approaches for achieving immune tolerance?

T cell depletion, bone marrow chimerism, regulatory T cell modulation, and co-stimulation blockade.

What benefits could immune tolerance provide for transplant patients?

Improved quality of life, reduced risk of secondary diseases, and better protection from infections and cancers.

What textbook is recommended for further reading on immunology?

Abbas Atl.

How is co-stimulation interference relevant to other lectures?

It will be further discussed in immune stimulation and cancer lectures.

What is a significant challenge faced with current transplant practices?

The huge waiting lists for available human organs.

What does clonal proliferation of T cells lead to?

An expansion of T cells that are reactive to the presented antigen.

What effect does blocking the B7 molecule have on T cells?

It prevents T cell activation by inhibiting the co-stimulatory signal.

What is one of the major areas of focus in strategies to induce immune tolerance?

Lymphocyte co-stimulation process interference.

How does immune tolerance improve patient outcomes?

By allowing their immune system to function normally without the risk of rejection.

What are the implications of natural inhibition of T cells through CTLA-4?

It is a mechanism to maintain tolerance and prevent overactive immune responses.

Why is it important to continue the search for tolerogenic drugs?

To achieve true immune tolerance and eliminate the need for lifelong immunosuppression.