Inflammation can increase expression of co-stimulatory

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1. Signalling through co-stimulatory receptors such as CD28 and CTLA4 are critical for the regulation of T cell activation.

a. Inflammation can increase expression of co-stimulatory ligands (such as CD80/86) on APC surfaces. Inflammation is thought to play a role in the causation of some autoimmune diseases, and inflammation can worsen autoimmune responses. Using what you know of T-cell activation and function, focusing on co-stimulatory receptor/ligand interactions, explain why inflammation may increase the risk of autoimmune diseases.

b. Abatacept is a CTLA-4-Ig fusion protein. It binds to CD80 and CD86, preventing CD80/86 from binding to both CTLA-4 and CD28. Abatacept can be used in the treatment of Rheumatoid Arthritis, an autoimmune disease. How would abatacept binding of CD80/86 help in the treatment of autoimmune disease?

c. There are both cancer treatments and autoimmune disease treatments that target CTLA4. Ipilimumab and tremelimumab are CTLA-4 blocking antibodies that are under clinical development for treatment of melanoma and other cancers (a blocking antibody binds to the target, CTLA-4, and prevents the natural ligand from binding, blocking signal from CTLA-4). How would a CTLA-4 blocking antibody enhance tumour responses?

Reference no: EM132416798

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