DrVirgo
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43. A 5-year-old boy with a history of recurrent ear infections receives his preschool booster immunization against diphtheria-tetanus-pertussis. He is participating in a community-sponsored study to determine the humoral immune response to tetanus toxoid (tt). His response is well below normal for age- and sex-matched children. Peripheral B lymphocyte count and T lymphocyte count and function are within the reference range. The antibody he makes is positive in both the passive hemagglutination and complement-mediated lysis of tt-coated erythrocytes. His antibodies do not opsonize tt-coated latex particles for phagocytosis and do not directly precipitate tt efficiently. This child most likely has a defect in which of the following processes?
A) Affinity maturation of immunoglobulins
B) Immunoglobulin isotype switching
C) Recombination of heavy chain variable region genes
D) Recombination of light chain variable region genes
E) Somatic mutation of immunoglobulin genes
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| DrVirgo
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Possible explanation from someone:
I think the answer is C.According to jawetz(page-341)IgG is the immunoglobulin that opsonizes.It can opsonize,ie.,enhance phagocytosis,because there are receptors for the gamma H chain on the surface of phagocytes.IgM does not opsonize directly,becuse there r no receptors on the phagocyte surface for the mu H chain.However,IgM activates complement,and the resulting C3b can opsonize because there r binding sites for C3b on the surface of phagocytes.
From this I understand that answer C is not letting the phagocyte receptor recognize the heavy chain so no direct precipitation,but the complement is still worknig as it works for IgM and the antibody is making C3b to indirectly cause lysis.
Tell me please if Im right.the groove for antigen is present on both heavy and light chain variable regions
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| usmle99
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firstly I did not understand so pls pls correct me if I am wrong...you say that the phagocyte receptor does not recognise the heavy chain ...then it should be ( whatever has happened ) in the constant region of the heavy chain..if there is IgM to activate the complement and there is no opsonization then why the ans should not be B?
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| endocrine
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I WLD ALSO GO WITH B
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| cyra
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The answer is B.
IgG antibodies are required for opsonisation.Since opsonisation is defective as described in the question...it has to be a defect in class switching(i.e from IgM to IgG).
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| enthu
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I go with B. as ig G is absent but IgM is present so class switching is affected...BUT DOES CLASS SWITCHING OCCUR BY RECOMBINATION OF HEAVY CHAIN REGIONS...if yes then it could be c also...plz someone explain how class switching occurs.
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| pearljam59
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Isotype switching:
TH2 cells secrete cytokine signals that act on B lymphocytes. As a result, the HEAVY CHAIN CONSTANT domains switch to classes of antibodies with new functions. FYI, once switching has occured it cannot go back.
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| DrVirgo
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Is it B or C... I'm still confused on this one????
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| robin082006
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I go with B too
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| DrVirgo
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Are:
C) Recombination of heavy chain variable region genes
D) Recombination of light chain variable region genes
Required for isotype switching?
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| amer_almohssen
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C and D are not needed for Isotype switching,
the only thing needed for switching is
1- an activated TH2 cell, and secretion of IL-4 ( for IgG, and IgE )
2-CD40 of the b-cell must bind to CD40 ligand of the TH cell
note that in the Q it says : "antibodies do not opsonize tt-coated latex particles for phagocytosis and do not directly precipitate tt efficiently" meaning that what ever Antibody that is there has a lower affinity(i.e: IgM ) then that which should be seen in a patient who has been exposed to this Antigen before.
thus the body is making antibodies, but not IgG.
so the right answer has to be ( B )
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| DrVirgo
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Ok, so final answer: B! 
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| waqastariq
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it is B...
class switching has nothing to do with the options C and D
thanks
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