NBME 2 spoiler

[Arista.MD]

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A protein contains a 30 aa structural motif with four cysteines coordinating by a zinc. In which of the following is it likely to be found.
transcription factor,
spliceosome,
ribosome,
ribonuclease,
nucleosome.


This is obvisously a zinc finger which literature indicates it can be a tx factor, assiated with the ribosone, or spliceosome. This is driving me insane. Does anyone know what is it?

Thanks.

 

[DOCTORSAIB]

A protein contains a 30 aa structural motif with four cysteines coordinating by a zinc. In which of the following is it likely to be found.
transcription factor,
spliceosome,
ribosome,
ribonuclease,
nucleosome.


This is obvisously a zinc finger which literature indicates it can be a tx factor, assiated with the ribosone, or spliceosome. This is driving me insane. Does anyone know what is it?

Thanks.

A) Transcription factor

Final answer.

 

[thgybhndthgy]

A question like this was on one of the NBME tests, and I can't figure out the correct answer (I'm thinking the answer is B). Anyone know it?:

After a full course of immunization with a new vaccine consisting of a recombinant polypeptide, 10% of adults fail to make antibody to the polypeptide. The nonresponders have an increased frequency of one HLA type. What is the most likely explanation for the failure of this group to respond to immunization?

A) Failure of B lymphocytes to recognize the polypeptide
B) Failure of T lymphocytes to recognize the polypeptide
C) Lack of class I MHC presentation of the polypeptide
D) Lack of class II MHC presentation of the polypeptide

 

[nrosigh]

The answer is D. The two clues are: 1) it's a subunit vaccine (as opposed to a live-attenuated virus, in which case the answer would be C), and 2) The nonresponders have a certain HLA type.

The B-cell receptor is an antibody derived from DNA splicing of VDJ genes, it has nothing to do with HLA type. The genes are on completely different chromosomes. Similar reasoning for why the T-cell receptor is not the correct answer.

Since the virus is a subunit vaccine, it does not replicate inside cells, and therefore MHC I plays no role. Therefore, the answer must be that MHC II does not properly present the peptide.

Let me know if you have any other questions from NBME 1-3 (haven't taken 4 yet)

A question like this was on one of the NBME tests, and I can't figure out the correct answer (I'm thinking the answer is B). Anyone know it?:

After a full course of immunization with a new vaccine consisting of a recombinant polypeptide, 10% of adults fail to make antibody to the polypeptide. The nonresponders have an increased frequency of one HLA type. What is the most likely explanation for the failure of this group to respond to immunization?

A) Failure of B lymphocytes to recognize the polypeptide
B) Failure of T lymphocytes to recognize the polypeptide
C) Lack of class I MHC presentation of the polypeptide
D) Lack of class II MHC presentation of the polypeptide

 

[thgybhndthgy]

Makes sense....but I was thinking that B might be correct because of anergy. Normally the reason why you see a disease associated with a certain HLA is because the combination of the antigen and MHC involved in antigen presentation are similar enough to something else in that person that they create autoantibodies (ex. HLA-B5 and Hashimoto's). In the scenario presented in the question, wouldn't it make sense that the polypeptide contained in the vaccine is still presented by the MHC molecule, but it is recognized as "self" instead of "foreign" (because of the mutated HLA) and thus the Helper T cell doesn't generate an immune response?

 

[nrosigh]

Your putting good thought into the question, but in autoimmune-prone HLA types, just the opposite happens. A specific combination of MHC I or II (depending on the disease) combines with a self-antigen to create a hyperactive T cell. What you described - all the T cells in the body failing to recognize a certain MHC-processed peptide, would be much less likely. Remember, T cells mature in the thymic cortex and are exposed to cells that have MHC I and MHC II on them. If the T cell failed to bind to MHC with sufficient affinity, then it would undergo apoptosis before it can become a mature T cell. Therefore, all T cells can bind to MHC I or II - this is called positive selection.

In case you have Parham's The Immune System, read p. 381. In case you don't this is what it says, "The vaccine [HBsAg] provides about 85% of those vaccinated with protective immunity against HBV infection. People who do not respond may lack an effective CD4 T-cell response because their HLA class II allotypes fail to present HBsAg-derived peptides."

Makes sense....but I was thinking that B might be correct because of anergy. Normally the reason why you see a disease associated with a certain HLA is because the combination of the antigen and MHC involved in antigen presentation are similar enough to something else in that person that they create autoantibodies (ex. HLA-B5 and Hashimoto's). In the scenario presented in the question, wouldn't it make sense that the polypeptide contained in the vaccine is still presented by the MHC molecule, but it is recognized as "self" instead of "foreign" (because of the mutated HLA) and thus the Helper T cell doesn't generate an immune response?

 

[thgybhndthgy]

Thanks for the reply.....this definitely makes much more sense.

 

[nrosigh]

No problem, thanks for bring up several important points that I needed to go over again.

I thought of something else, too:

The way B cells are stimulated to make antibody is:
1) B cells recognize antigen with their B-cell receptor (membrane-bound antibody)
2) Antigen-receptor complex endocytosed and fragments of the original antigen are processed and displayed on MHC II.
3) T-helper cells recognize antigen-MHC II complex and activate B-cells with CD40 and cytokines (IL-4).

If an antibody failed to be produced, there would be no way to differentiate errors in step 1 from step 3.

Thanks for the reply.....this definitely makes much more sense.