Immunology: central tolerance and AIRE: practice question

A Microbiology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Microbiology · Immunology: central tolerance and AIRE

Sample item

An 8-year-old boy has chronic mucocutaneous candidiasis, then hypoparathyroidism and later adrenal insufficiency. Multiple endocrine organ antibodies are found. Which defect is most likely?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

D. Mutation of AIRE, impairing thymic negative selection of self-reactive T cells

AIRE is a transcription regulator in thymic medullary epithelial cells that drives expression of tissue-specific antigens so that self-reactive T cells are deleted. Its loss causes autoimmune polyendocrine syndrome type 1 with candidiasis, hypoparathyroidism and Addison disease. The candidiasis arises from neutralising autoantibodies against IL-17 and IL-22.

Option by option

  • A. Mutation of ADA, causing lymphocyte apoptosis

    ADA deficiency causes severe combined immunodeficiency presenting in infancy with profound lymphopenia.

  • B. Mutation of CD40 ligand, impairing isotype switching

    CD40 ligand deficiency causes hyper IgM syndrome with opportunistic infections but not multi-endocrine autoimmunity.

  • C. Mutation of FOXP3, causing absent regulatory T cells

    FOXP3 mutation causes IPEX, with neonatal diabetes, enteropathy and eczema, and does not typically produce candidiasis with hypoparathyroidism.

  • D. Mutation of AIRE, impairing thymic negative selection of self-reactive T cells (correct)

    AIRE deficiency allows self-reactive T cells to escape deletion and produces this triad.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Microbiology question

What is the answer to this Microbiology question?

The best answer is D, Mutation of AIRE, impairing thymic negative selection of self-reactive T cells. AIRE is a transcription regulator in thymic medullary epithelial cells that drives expression of tissue-specific antigens so that self-reactive T cells are deleted.

Why is "Mutation of ADA, causing lymphocyte apoptosis" not the answer?

ADA deficiency causes severe combined immunodeficiency presenting in infancy with profound lymphopenia.

Why is "Mutation of CD40 ligand, impairing isotype switching" not the answer?

CD40 ligand deficiency causes hyper IgM syndrome with opportunistic infections but not multi-endocrine autoimmunity.

Why is "Mutation of FOXP3, causing absent regulatory T cells" not the answer?

FOXP3 mutation causes IPEX, with neonatal diabetes, enteropathy and eczema, and does not typically produce candidiasis with hypoparathyroidism.

What concept does this question test?

It tests Immunology: central tolerance and AIRE in Microbiology. Its loss causes autoimmune polyendocrine syndrome type 1 with candidiasis, hypoparathyroidism and Addison disease. The candidiasis arises from neutralising autoantibodies against IL-17 and IL-22.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Immunology: central tolerance and AIRE?

Make a one-line identity card for each organism: shape and stain, defining test, toxin, disease and drug. Then use the flashcards and the other Microbiology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.