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Both Bcells and Tcells undergo somatic recombination to generate epitopespecific receptors and are a

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Thus, most T-cells actually become anergic when they first encounter a tumor cell. ... The cell type in the bone marrow that is almost exclusively responsible for ... – PowerPoint PPT presentation

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Title: Both Bcells and Tcells undergo somatic recombination to generate epitopespecific receptors and are a


1
Both B-cells and T-cells undergo somatic
recombination to generate epitope-specific
receptors and are also screened for
autoreactivity. In addition to these two
processes, double-positive T-lymphocytes also
undergo a process that will determine their
individual functions (helper, cyotoxic,
regulatory). This determination of function is
essentially happening at the same time as
positive selection (to establish MHC
restriction). Thus, the determination of
function will involve which one of the following
sets of molecules cells? (select ONE letter
that has the correct set)
  • A. dendritic cells presenting self-peptides using
    MHC Class I and HLA-DP,DQ,DR to present these
    peptides
  • B. bone marrow stromal cells using weak and
    strong adhesion molecules and secreting
    Interleukin-7 (IL-7)
  • C. thymic cortical epithelial cells presenting
    NON-self-peptides using MHC Class I and MHC Class
    II to present these peptides (this ensures that
    no autoimmune response will occur during this
    phase of T-cell development)
  • D. thymic cortical epithelial cells presenting
    self-peptides using MHC Class I and MHC Class II
    to present these peptides

2
For several different aggressive tumors, many
immunologists suggest that a reason why very
little or no T-cytotoxic-mediated tumor cell
killing takes place is due to the lack of any
significant priming of those T-cells by
dendritic cells. Thus, most T-cells actually
become anergic when they first encounter a tumor
cell. What might be a reason why this priming
does not take place?
  • A. dendritic cells are not very capable of
    presenting non-self tumor peptides
  • B. dendritic cells may not have engulfed and
    processed any non-self tumor peptides (especially
    if the tumor is a new one in that body)
  • C. no tumor peptides are suitable for
    presentation by HLA-A,B,C presenting molecules
  • D. priming is an event that takes place mainly in
    the lymph nodes and there are virtually no
    dendritic cells found in any lymph nodes at any
    time

3
Many tumor vaccines attempt to overcome the
lack of T-cell priming in one of two different
ways. One is a rather interesting alteration of
expression of surface molecules by the tumor
cells themselves. Which one of the following
alterations might actually work (and, indeed, has
been successful in animal experimentation)?
  • A. change a few tumor cells so they express B-7
    and thus would be capable of priming unprimed
    T-cells.
  • B. eliminate the presence of ANY MHC Class I
    peptide-presenting molecules on the tumor cell
    surface
  • C. alter proteosome degradation of tumor proteins
    the cytoplasm so that the resulting peptides can
    bind with high affinity to MHC Class II
    presenting molecules
  • D. remove any cell-adhesion molecules from the
    surfaces of a few of the patients tumor cells

4
Isotype transplacental
  • A. IgG
  • B. IgA
  • C. IgM
  • D. IgD

5
Very recent clinical research into possible
immunology-based therapies to reduce the (often
severe) allergic reactions to nuts (peanuts and
tree nuts) suggests that the isotype switch from
IgE to IgG may be a real outcome of allergy shots
(desensitization). Based on this observation
(isotype switch), you would conclude that the
injected allergen appears to be influencing which
one of the following types of cells to alter that
cells signals that affect isotype selection?
  • A. dendritic cell
  • B. T-helper1 cell
  • C. mast cell
  • D. T-helper2 cell
  • E. phagocyte (using Toll-like receptors as the
    signaling mechanism)

6
In order for the allergens (most likely proteins)
to alter the T-helper2 cell cytokine production
(to change the isotype produced by a B-cell from
IgE to IgG), at least one peptide must be
presented to that TH2 cell so that the correct
molecular interaction takes place as a signal to
that T-cell select one answer from below that
describes this presentation to the TH2 cell
(probably being presented by a B-lymphocyte).
  • Peptide of 8-10 amino acids presented by an MHC
    Class I
  • Peptide with a size of 10-30 amino acids
    presented by an MHC Class I
  • Peptide with a size of 10-30 amino acids
    presented by an MHC Class II
  • Peptide that has been generated by degradation of
    a large protein by a set of enzymes called the
    proteosome

7
An invariant chain temporarily occupies the
peptide-binding groove of an HLA-DP molecule
while it is still in the ER. The function of
this chain is two-fold. One function is to
prevent the inadvertent binding of any peptides
that are in the ER to the HLAs groove. The
second function of this binding is which one of
the following?
  • A. to maintain the stability of the HLAs alpha
    chain until it (the HLA) is fully assembled in
    the ER
  • B. to signal the HLA to move from the ER in a
    membrane-bound vesicle that will eventually fuse
    with another vesicle that contains fragments of
    degraded molecules, including peptides
  • C. to remove the CLIP (Class II-associated
    Invariant chain peptide) from the groove of the
    HLA to allow it to bind a peptide after the
    fusion of its vesicle with another vesicle that
    contains fragments of degraded molecules,
    including peptides
  • D. to prevent inhibition of TAP-assisted
    transport by certain infectious viruses

8
HLA distribution on human cells appears to
correlate very closely with the potential need
for a cell to present peptides using those HLAs.
For example, HLA-A, HLA-B, HLA-C are likely to be
expressed on which one of the following sets of
cells?
  • A. only virus-infected cells (and not normal,
    uninfected cells)
  • B. only on cells that are involved in seeking
    help from T-helper cells
  • C. any cell in the body that has a nucleus (i.e.,
    all leukocytes)
  • D. only red blood cells, especially in persons
    who are anemic

9
The presentation of self-peptides by certain
types of human HLAs is a very common process
carried out by virtually every cell in the body.
This on-going process is thought to be
responsible for maintaining this presentation
system so that it is ready if the cell were ever
to be threatened and it needed to send a signal
to be killed. However, this presentation of
self-peptides is thought to be partially
responsible for which one of the following very
undesirable responses?
  • A. a potentially severe allergic reaction
  • B. the suppression of an on-going adaptive immune
    response against a developing tumor cell
  • C. an autoimmune response
  • D. depletion of a large percentage of memory
    T-cytotoxic cells due to the lack of cytokine
    expression by TH1 cells

10
Which one of the following might be a predictor
of the possibility of a person developing an
autoimmune disease?
  • A. the lack of an enzyme function that is
    important in the development of B-lymphocytes,
    which would result in no functional
    B-lymphocytes)
  • B. an underdeveloped (or dysfunctional) thymus,
    which would likely result in very few, or even
    no, functional T-lymphocytes of any kind
  • C. the particular set of A,B,O red blood cell
    antigens that constitutes that persons red blood
    cell type
  • D. the particular set of HLA-A,B,C,DP,DQ,DR that
    constitutes that persons tissue type

11
The creation of a fully functional
epitope-specific receptor on the surface of a
B-lymphocyte would involve how many different
gene fragments (from the various V,D,J gene
fragments)
  • A. FIVE - a VDJ for the variable portion of the
    heavy chain and a VJ for a the variable potion
    of the light chain
  • B. THREE a VDJ for the variable portion of
    the heavy chain and the same VJ for the variable
    portion of the light chain
  • C. TWO one gene fragment (V) for the complete
    variable portion of the heavy chain and one gene
    fragment (J) for the complete variable portion of
    the light chain
  • D. at least 1x108 gene fragments would be used,
    since the total number of specificities that can
    be generated during somatic recombination is at
    least this high

12
B-lymphocytes that do develop epitope receptors
specific for self-peptides (as a result of
somatic recombination) can be eliminated or
rendered unresponsive (called anergy). However,
this elimination/anergy will only happen if the
B-cell is still in the immature state and the
epitope is encountered (by the receptor) after
the time that one isotype version of the complete
functional receptor is expressed on the cell
surface and before the second isotype version is
expressed. Thus this B-cell is susceptible to
elimination/anergy during which one of the
following stages of its development?
  • A. after the expression of the IgD version of
    the receptor and before the expression of the IgM
    versionB. after the expression of the IgM
    version and before cytokine-induced isotype
    switching to the very versatile IgG versionC.
    after the expression of a pre-B receptor
    (complete heavy chain and surrogate light
    chain) and before the expression of the fully
    functional IgM isotype version of that
    receptorD. after the expression of the IgM
    version of the receptor and before the expression
    of the IgD version

13
The cell type in the bone marrow that is almost
exclusively responsible for initiating the
development of a stem cell into a B-lymphocyte is
which one fo the following?
  • A. a T-helper cell, as the selection of the
    isotype of the developing epitope-receptor is
    controlled by cytokines
  • B. a dendritic cell, since the presentation of
    peptides is a very important step in initiating
    an immune response
  • C. a stromal cell expressing certain adhesion
    molecules and, eventually, secreting
    interleukin-7 (IL-7)
  • D. endothelial cells expression weak adhesion
    molecules along the high endothelial venule (HEV)

14
Basically what happens if you are sick (no flu)
and you get a flu shot (injected)?
  • A. You will not develop any immunity for flu
  • B. um, the symptoms of your current illness will
    disappear MUCH more rapidly compared to persons
    who did not get the flu shot
  • C. you will get the flu
  • D. you will likely (eventuallly) develop an
    immunity (no lifetime, given the inactivated form
    of the flu virus vaccine)

15
Fully mature B-cell would be which one of the
following?
  • A. IgM IgD versions of the BCR
  • B. Has undergone apoptosis during check for
    self-specificity
  • C. has a receptor that consists of IgM jeavy
    chain and surrogate light chain and Igalpah and
    Igbeta flanking chains
  • D. When CD3 flanking molecules appear
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