Question

1.

Cyclosporin A and rapamycin are each used as T cell immunosuppressants. They share the property of binding to immunophilin molecules in T cells as the initial step in their mechanisms of action. However, in the case of cyclosporin A, the drug:immunophilin complex binds to and inhibits the protein phosphatase calcineurin, whereas the rapamycin:immunophilin complex binds to and inhibitors mTOR. As a consequence

a. Cyclosporin A, but not rapamycin, blocks cytokine production by T cells.

b. Both cyclosporin A and rapamycin block cytokine production by T cells.

c. Both cyclosporin A and rapamycin inhibit co-stimulatory signaling through CD28 on T cells.

d. Rapamycin, but not cyclosporin A, blocks T cell proliferation.

e. Neither rapamycin nor cyclosporin A block T cell proliferation.

2.

One early study on DNA vaccines examined the CD8 T cell response to the plasmid-encoded antigenic protein following subcutaneous immunization of mice with the plasmid DNA. This study used bone marrow chimeras to distinguish the MHC class I alleles expressed on bone marrow-derived cells from those expressed on all other mouse cells and tissues. When analyzed, the data showed that antigen-specific CD8 T cell responses were restricted to the MHC class I alleles derived from the donor bone marrow. These findings indicate that a key step in DNA vaccination is:

a. The presentation of peptides derived from the antigenic protein on MHC class I molecules of skin-resident dendritic cells

b. The expression and secretion of the plasmid DNA-encoded antigenic protein by skin keratinocytes

c. The stimulation of keratinocytes to produce inflammatory cytokines in response to the plasmid DNA-encoded antigenic protein

d. The uptake of the plasmid DNA by antigen-presenting cells in the skin

e. The trafficking of the plasmid DNA-encoded antigenic protein to the draining lymph nodes of the skin for uptake by phagocytic cells

Answer 1

Answer 1: “B” Both cyclosporin A and rapamycin block cytokine production by T cells

Rapamycin disrupts cytokine signalling that promotes lymphocyte proliferation and cyclosporin A block the transcription of cytokine genes in activated T cells.

It is also observed that cyclosporin is much less effective in inhibition of the production of cytokines when T cells have received CD28 signals hence statement “ C” does not hold true.

Answer 2 “A” The presentation of peptides derived from the antigenic protein on MHC class I molecules of skin-resident dendritic cells

In DNA vaccines expression vectors are constructed to express a gene product which will serve as immunogen.It is an ideal approach for designer vaccine candidate as antigens can be modified through rDNA technology and endogenously expressed antigens can be enter class 1 MHC to give CD8 T cell response