Question

1.

Corticosteroids are anti-inflammatory drugs that are used to treat individuals with allergies, asthma, autoimmune diseases, or organ transplants. These compounds have a wide range of effects on leukocytes and on inflammatory cytokine production. One common use for corticosteroids is as an inhaled treatment for individuals with asthma. Interestingly, inhaled corticosteroids provide significant benefit to asthma patients with high numbers of eosinophils in their airways, but not to those patients with high numbers of neutrophils, but normal numbers of eosinophils. One reason for this finding may be that:

a. Corticosteroids don’t inhibit release of IL-33 by airway epithelial cells

b. Corticosteroids induce apoptosis of T_reg cells

c. Corticosteroids don’t work well as combination therapy with other immunosuppressants

d. Corticosteroids induce apoptosis of eosinophils

e. Corticosteroids don’t inhibit IL-13 production in the airways

2.

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.

3.

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 :-

1. Interleukin-33 is a cytokine that is basically associated with activation of helper T-lymphocytes and eosinophils although there is no association with neutrophils. Basically, corticosteroids are used to prevent the effects posed by immunological responses in the form of allergies,etc. Hence, it is important that the activity of IL-33 needs to be stopped which in turn can be initiated by Corticosteroids. This in turn prevents inflammatory response. Hence, option 'A' is not correct as it states that Corticosteroids dont inhibit release of IL-33 by epithelial cells of airway.
2. Regulatory T-cells (TReg) are basically produced by the Thymocytes which are precursor cells produced in the thymus. It is stated to induce apoptosis of the Thymocytes although its inhibiting activity is only limited to the Thymocytes and not the TReg cells. Although as the TReg cells are associated with immunosuppressive effect, there is no apoptosis associated with them and hence option 'B' is not correct which states that Corticosteroids induce apoptosis of the TReg cells.
3. For the third option, the term should be stated as immunomodulation. In this case, a combined therapy is given in order to ensure the condition of inflammation doesn't worsen and at the same time it should be taken into consideration that there are certain barriers lining the heart and lungs apart from the alveolar macrophages which in turn provides the temporary defense against infections. So, the option 'C' is not appropriate.
4. IL-13 is also a cytokine which is associated with inflammatory response and hence corticosteroids will tend to show a similar effect as was seen in case of IL-33 in order to reduce the effect of inflammation. So, option 'E' which indicates that Corticosteroids does not inhibit IL-3 production is not correct.
5. The most appropriate answer is option 'D'. In case of eosinophils associated asthma, there is elevation in the number of eosinophils. This is the target for the corticosteroids which in turn leads to apoptosis of the cells to reduce inflammation. So, this is most correct option.

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