Try this immuno Quest !!

[sunny]

A 7 day old newborn is brought to the physician by his mother for tetanic contractions of his arms and legs. Physical examination shows low set ears, and vertically elongated mouth and profile. A chest X Ray shows absence of thymic shadow. Which of the following immunologic parameters is most likely to be normal in this newborn??

A. Antibody-dependent Cell mediated cytotoxicity
B. Cytotoxic T-lymphocyte production
C. Delayed-type hypersensitivity
D. Gamma-delta T-cell numbers
E. Immunoglobulin A production

Please post reason along ..

[aktorque]

My ans is E)Immunoglobulin A production

Dx
DiGeorge syndrome

Explanation:
http://en.wikipedia.org/wiki/DiGeorge_syndrome

[doctorsmonsters]

E it is because all other options have T cells involved which wont be happening in this kid as he doesn't have a thymus. IgA production is B cell function, which will be normal.

[doc_study]

I dont know what these Gamma-delta T-cell are......
but i think for all other options we would require intact Helper T cell function.

[usluipek]

Is the tetanic limb contraction related to the diGeorge Syndrome?

[doctorsmonsters]

Originally Posted by usluipek

Is the tetanic limb contraction related to the diGeorge Syndrome?

It has something to do with calcium levels.

[usluipek]

Yes, the tetany is due to hypocalcemia as a result of parathyroid gland malformation.

[apx85]

I would go with E because it is the only process, from my understanding, that does not require T-cells of the choices given. The thymus is where T-cells differentiate and mature so without a thymus, all T-cell functions will be absent.

B-cell function should still be preserved, allowing for antibody production. So my answer is E

I'm trying to think of the diagnosis, but I can't be sure. Is it Edward's??

[apx85]

Hmm I should have known that. Got caught up on low set ears and vertically elongated face.

No thymus = DiGeorge's...got it

[cp25]

I thought you needed T helper functions for class-switching to IgA...
I was going to say Antibody-dependent cell mediated citotoxicty, but It also required IgG

[silenttmutation]

diagnosis: di georges
ans: gamma delta T cell numbers

I'm pretty sure this is the answer because gamma delta t cells are thymus independent and mature in the bone marrow (not a 100% sure about this explanation)

[Triquetrum]

Hello, I'll give some input. The question basically describes a DiGeorge Sd (no thymus; no parathyroid -> hypocalcemia -> tetany), so basically a T-cell deficiency... it's a neonate,, therefore, I don't think delayed type hypersensitivity such as PPD reaction o contact dermatitis (e.g. contact to nickel) would be seen yet. IgA deficiency would clearly describe a child with body secretion deficiency so...E.

[apx85]

doc_study, cp25, silentmutation

I think you are right with D. IgA would definitely not be present because class-switching is a Thymus dependent process (need mature CD4 T-cells with CD40-CD40L interaction).

From what I recall about T-cell development, there are two different types of T-cell receptors, alpha-beta (make up the vast majority of T-cells) and delta-gamma. The T-cell receptor is made in the bone marrow and then T-cells travel to the Thymus to differentiate and mature into CD4+ or CD8+ (or apoptosis). Therefore, the formation of gamma-delta T-cells is not impaired in a patient without a Thymus using this logic.

I could not find a source to confirm this, but then again I didn't look too long.

Great question!

[Triquetrum]

sorry, IgA is found in secretions.

[salz]

ans is D
I dont know why my post was del. it is not E cuz for class switching we still need t helper cells th2!

[Zeeshan ali]

E is my ans...

so guys, which is the correct one???

[1TA2B]

Mnemonic CATCH-22 to describe DiGeorge's syndrome, with the 22 to remind one the chromosomal abmormality is found on the 22 chromosome, as below: Cardiac Abnormality (especially tetralogy of Fallot)
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcemia.


(http://en.wikipedia.org/wiki/DiGeorge_syndrome)

[sunny]

Originally Posted by doc_study

I dont know what these Gamma-delta T-cell are......
but i think for all other options we would require intact Helper T cell function.

Yes, spot on doc. Ans is D.

[sunny]

Well tried guys.
Here s the explanation.
The catch is mong options D & E.
It is a case of DiGeorge Syndrome.
Gamma-delta T-cells are the only category of T-cells that do not require education and selection in the thymus. They possess a T cell receptor that has Gamma and Delta chains instead of more common ( 95 to 99 % of all T-cells ) alpha-beta T Cell receptor. The function of gamma-delta T cells is unknown, but they make up the majority of cells in the submucosa and intraepithelial spaces, and it is therefore hypothesized that they play a role in protection against a limited repertoire of antigens that enter the body across epithelial barriers.

Immunoglobulin A production requires the cytokines of TH2 cells to cause the isotype switch in B lymphocytes. TH2 cells require thymic education.

A challenging question indeed.
Looking forward to post some more questions in future involving the catch.

Good luck to everyone.

[aktorque]

That was a challenging one.... Great qn buddy.

[m82_ghasemi]

Originally Posted by apx85

doc_study, cp25, silentmutation

I think you are right with D. IgA would definitely not be present because class-switching is a Thymus dependent process (need mature CD4 T-cells with CD40-CD40L interaction).

From what I recall about T-cell development, there are two different types of T-cell receptors, alpha-beta (make up the vast majority of T-cells) and delta-gamma. The T-cell receptor is made in the bone marrow and then T-cells travel to the Thymus to differentiate and mature into CD4+ or CD8+ (or apoptosis). Therefore, the formation of gamma-delta T-cells is not impaired in a patient without a Thymus using this logic.

I could not find a source to confirm this, but then again I didn't look too long.

Great question!

Gamma-Delta T cells and Alpha-Beta T cells arise from a common progenitor cell in the thymus. The molecular events leading to the lineage decision of developing CD4- CD8- thymocytes to differentiate into Gamma-Delta T cells versus Alpha-Beta cells have not been fully resolved.

Reference: http://mcb.berkeley.edu/labs/raulet/...07-03xiong.pdf


Humoral immunity is mostly unaffected in Di George Syndrome, but selective IgA deficiency occurs in up to 13% of patients. It means that more than 70% of patients have normal IgA levels. Selective IgM deficiency associated with 22q11.2 deletion has been reported in 1 patient.

Reference: http://www.ncbi.nlm.nih.gov/pubmed?t...rge%20Syndrome

Therefore, I would say E.