h*******r
发帖数: 182 | 1 After a full course of immunization with a new vaccine consisting a
recombinant polypeptide, 10% of adults fail to make antibody to the
polypeptide. The nonresponsers have an increased frequeny of one HLA type.
What is the most likely explannation for the failure fo theis group to
respond to immunization.
B
A. Failure of B lymphocyte to recognize the polypepetide
B. Failure of T lymphocyte to recognize the polypepetide
C. Lack of class I MHC presentation of the polypeptide
D. Lack of class II MHC presentation of the polypeptide
Given answer is D.
My answer is B. When polypeptide was injected into body, they bind to MHCII
on B cell, which presented to T cells and in turn release IL-2, 4, 6, 10 etc
for activating B into plasma cell. Nonresponders failed to make ab and have
increased frequency of one HLA type, so it is likely that this peptide
mimick HLA DQ, DP, DR(MHC II). And T cells that bind with strong affinity to
self MHC II (similar to this peptide) have undergo apoptosis in the thymus
(negative selection).
A. is not correct. If B does not recognize the peptide, it would be due to
lack of epitope at membrane-bound IgM. This is unlikely considering 10% the
population with so many possible of hypermutations to creat likely epitopes.
Besides, increased HLA type cannot be used as the clue of the question.
C. not correct. class I is for CMI, not for Ab
D. not correct. It says increased frequency of HLA type.
Thanks for your helps and comments. | i**********d
发帖数: 853 | 2 请问，你讲的“When polypeptide was injected into body, they bind to MHCII
on B cell,”这一句话有什么依据么？ | h*******r
发帖数: 182 | 3 B cell is one kind of antigen presenting cell in addition to Macrophage (
specialized in fighting and presenting antigens from intracellular
microbes
such as Listeria, Mycobacteria, Leishmania, Histoplasma etc. therefore
initiate CMI), dendritic cells (skin, contact dermatitis), endothelial
cells
(Acute Graft rejection).
B cell also can mount non-memory humoral reaction against polysaccharide
antigen by producing IgM without T cell's help. But polypeptide usually
leads to reaction that mediated by TH2.
【在 i**********d 的大作中提到】
: 请问，你讲的“When polypeptide was injected into body, they bind to MHCII
: on B cell,”这一句话有什么依据么？
| i**********d
发帖数: 853 | 4 谢谢回复，我之所以问这个问题是因为：从外来抗原被注射入体内，到APC细胞把它和
MHC II的complex表达在细胞膜上之间有一些复杂的步骤，我个人认为这中间的过程是
解释这个题的关键所在。
基本步骤：
1. Exogenous antigens, such as viruses, are engulfed and placed in a
phagosome.
2. Lysosomes fuse with the phagosome forming a phagolysosome.
3. Protein antigens are degraded into a series of peptides.
4. MHC-II molecules are randomly synthesized in the endoplasmic reticulum;
since MHC is very complicated system and can form numerous different MHC II
molecules, in most time at least one MHC II molecule can fit the degraded
peptide.
8. The MHC-II molecules with bound peptides are transported to the
cytoplasmic membrane where they become anchored. Here, the peptide and MHC-
II complexes can be recognized by T4-lymphocytes by way of TCRs and CD4
molecules having a complementary shape.
So, in the stem of this question, it mentioned “nonresponsers have an
increased frequency of one HLA type.” I think this ‘increased frequency of
one HLA type’ is the reason why the APC can’t find one MHC II molecule to
efficiently bind to the antigen peptide. As a result, there is a ‘Lack of
class II MHC presentation’ and then there is a failure to produce the
antibodies.
【在 h*******r 的大作中提到】
: B cell is one kind of antigen presenting cell in addition to Macrophage (
: specialized in fighting and presenting antigens from intracellular
: microbes
: such as Listeria, Mycobacteria, Leishmania, Histoplasma etc. therefore
: initiate CMI), dendritic cells (skin, contact dermatitis), endothelial
: cells
: (Acute Graft rejection).
: B cell also can mount non-memory humoral reaction against polysaccharide
: antigen by producing IgM without T cell's help. But polypeptide usually
: leads to reaction that mediated by TH2.
| h*******r
发帖数: 182 | 5 The logic that increase of HLA type leads to inability of MHC binding to
antigen peptide is not reasonable. What I believe is that this increase HLA
type is more like the peptide, therefore these people will not produce
antibody. This is called anergy. Otherwise autoimmune disease will ensue.
Opposite example is rheumatic fever post-streptococcus infection(Type II
hypersensitivity against heart, joint, brain tissue), or more accuarately
like PAIR that happened after Clamydia or Campy infection. | a*******r
发帖数: 8 | 6 D is right.
Because not only Th can provide Ag using MHCII, DC cell can also provide Ag.
So 10% people can not produce antibody, because DC and Th lack that kind
of MHCII and can not recognize and bind to Ag, then transfer to B cell and
B cell produce antibody.
【在 h*******r 的大作中提到】
: After a full course of immunization with a new vaccine consisting a
: recombinant polypeptide, 10% of adults fail to make antibody to the
: polypeptide. The nonresponsers have an increased frequeny of one HLA type.
: What is the most likely explannation for the failure fo theis group to
: respond to immunization.
: B
: A. Failure of B lymphocyte to recognize the polypepetide
: B. Failure of T lymphocyte to recognize the polypepetide
: C. Lack of class I MHC presentation of the polypeptide
: D. Lack of class II MHC presentation of the polypeptide
| h*******r
发帖数: 182 | 7 Many people would choose D, and I think this is a common logic--no MHCII,
then APC cannot present Ag. But one underlying fact most people missed is
that this deficiency (Bare lymphocyte) would leads to complete loss of CD4+
cells, one kind of rare SCID that will not respond to any foreign Ag
including microbes. There is no evidence that in such population one HLA
phenotype will increase its expression.
BTW, T cells are not APC.
Ag.
and
【在 a*******r 的大作中提到】
: D is right.
: Because not only Th can provide Ag using MHCII, DC cell can also provide Ag.
: So 10% people can not produce antibody, because DC and Th lack that kind
: of MHCII and can not recognize and bind to Ag, then transfer to B cell and
: B cell produce antibody.
| a*******r
发帖数: 8 | 8 All right, just disscussion.
But the question topic is try to find the 10% vaccine deficiency in normal
people group, like one certain people will never get HIV.
According this question, my logic is very simple, both Th and APC with MHCII
can induce antibody from B cell, so only T cell lack ....can not induce
deficiency of antibody in normal person. Then b is not right. :)
+
【在 h*******r 的大作中提到】
: Many people would choose D, and I think this is a common logic--no MHCII,
: then APC cannot present Ag. But one underlying fact most people missed is
: that this deficiency (Bare lymphocyte) would leads to complete loss of CD4+
: cells, one kind of rare SCID that will not respond to any foreign Ag
: including microbes. There is no evidence that in such population one HLA
: phenotype will increase its expression.
: BTW, T cells are not APC.
:
: Ag.
: and
| m********k
发帖数: 69 | 9 Answer should be D.
Please notice this sentence: The nonresponsers have an increased frequeny of
one HLA type. This does not mean the lack of MHCII molecule expression ,
but means that this MHC II molecule can not bind and present the recombinant
polypeptide to Th cell and no immunologic reaction is induced. Meanwhile,
the responsers express other HLA subtypes instead in the same gene locus,
which can present the polypeptide to Th cell and then induce the production
of Ab.
As for negative selection, it deletes the T cell clones which have strong
reactivity to self antigen. But the clones with normal reactivity are still
there. These normal T cell clones mediate the type II hypersenstivity of
Rheumatic fever and pemphigus.
【在 h*******r 的大作中提到】
: After a full course of immunization with a new vaccine consisting a
: recombinant polypeptide, 10% of adults fail to make antibody to the
: polypeptide. The nonresponsers have an increased frequeny of one HLA type.
: What is the most likely explannation for the failure fo theis group to
: respond to immunization.
: B
: A. Failure of B lymphocyte to recognize the polypepetide
: B. Failure of T lymphocyte to recognize the polypepetide
: C. Lack of class I MHC presentation of the polypeptide
: D. Lack of class II MHC presentation of the polypeptide
| h*******r
发帖数: 182 | 10 Thanks for your answer, motherduck.
During group discussion, our members also pointed out I misunderstood answer
D. It says Lack of MHC-II presentation, not Lack of MHC-II. I try to find
the theoretic basis by which increase of one MHC-II type would interfere
with antigen presentation. Another word, what kind of diseases or defects (
genetic) do you know that are due to blunted immune response with specific
HLA type? We learned that HLA B27(MHC-I) predisposes to PAIR, HLA DR3/4(MHC-
II) to DM I..., these examples are more like over-response with some HLA
phenotypes.
Thanks again.
of
,
recombinant
production
still
【在 m********k 的大作中提到】
: Answer should be D.
: Please notice this sentence: The nonresponsers have an increased frequeny of
: one HLA type. This does not mean the lack of MHCII molecule expression ,
: but means that this MHC II molecule can not bind and present the recombinant
: polypeptide to Th cell and no immunologic reaction is induced. Meanwhile,
: the responsers express other HLA subtypes instead in the same gene locus,
: which can present the polypeptide to Th cell and then induce the production
: of Ab.
: As for negative selection, it deletes the T cell clones which have strong
: reactivity to self antigen. But the clones with normal reactivity are still
| m********k
发帖数: 69 | 11 “what kind of diseases or defects (genetic) do you know that are due to
blunted immune response with specific HLA type。 ”------
I have no idea on your question. However, I have heard a story from my
friend who focus on HBV study. They found a population resistant to HBV
hepatitis, because their hepatic cell fail to present the HBV antigen. This
case is similar to the NBME question you mentioned. Hope it is helpful for
you to understand that question. | h*******r
发帖数: 182 | 12 Thanks for taking time answering my question.
For HBV infection, I guess that would be lack of MHC-I. That is reminiscent
of some white population lacking cytokine receptor is resistant to HIV
infection. It is very interesting.
This
【在 m********k 的大作中提到】
: “what kind of diseases or defects (genetic) do you know that are due to
: blunted immune response with specific HLA type。 ”------
: I have no idea on your question. However, I have heard a story from my
: friend who focus on HBV study. They found a population resistant to HBV
: hepatitis, because their hepatic cell fail to present the HBV antigen. This
: case is similar to the NBME question you mentioned. Hope it is helpful for
: you to understand that question.
|
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