Immunology Questions II

Dave Rintoul drintoul at ksu.ksu.edu
Wed Sep 28 11:33:55 EST 1994


More questions - any and all comments, corrections will be
appreciated.  These are more complete; i.e. they have answers! I will
spare you from the earliest questions, which are basically fill-in the
blanks, multiple choice etc.  These middling hard questions are
entitled:

PART C: Putting Concepts to Work

31. The immunoglobulin molecule has two major structural domains, the
antigen-binding domain and the effector domain. How do these
structural domains relate to the function(s) of an immunoglobulin
molecule?

The structural domains reflect functional distinctions.  The antigen
binding domain functions in recognition and specificity of foreign
antigens.  The effector domain functions as a membrane anchor, or as a
site for recognition of specific soluble proteins or other membrane
bouind proteins.  Binding of other proteins (e.g. complement) to the
effector domain is necessary for specific functions.

32. A scientist injects a purified bacterial enzyme into two different
rabbits in order to cause the rabbits to generate specific antibodies
against the enzyme. Later, serum from these two rabbits contains
significant quantities of specific antibodies, since co-incubation of
the serum and the purified enzyme produces large aggregates (see Fig.
27-2 of MCB). However, serum from only one of the rabbits is capable
of inhibiting the activity of the enzyme. What is the simplest
explanation for this observation?

One (or more) of the antibodies in the inhibitory serum is specific
for the active site of the enzyme; i.e., the active site is an epitope
for this antibody. The non-inhibitory serum does not contain any
antibodies which reecognize the enzyme active site.

33. Why does IgM have such a high binding avidity for viruses, or
other pathogens that are covered with identical subunits?

Because it has multiple, closely spaced binding sites.

34. Antibodies can be denatured and then renatured in the absence of
antigen. Antibodies treated in this manner retain the same binding
specificity. Is this observation consistent or inconsistent with the
instructive theory of antibody diversity? Explain your reasoning.

This observation is inconsistent with the instructive theory of
antibody diversity. The instructive theory predicts that antibody
specificity arises from an interaction with the antigen, causing it to
fold in a specific way and generating a high affinity binding site for
that particular antigen.  If antibody re-folding in the absence of
antigen still produces an antibody with the same specificity that it
previously had, the specificity must not be due to antigen/antibody
interactions during folding.

35. Myelomas secrete large quantities of a single specific antibody.
This observation has had a major impact on the field of immunology in
at least two different ways.  What advances in immunology can be
traced to this observation?

Antibodies secreted by myelomas were purified and used to determine
the structure of the immunoglobulin protein. The observation that only
a single type of antibody can be produced by a myeloma clone was also
an additional proof of the clonal selection theory of antibody
diversity.

36. What are the three possible fates of a virgin B lymphocyte?

A virgin B cell may never encounter antigen, in which case it will die
after a few days in circulation. If antigen is encountered, the cell
will divide and generate two types of progeny. One is the
immunoglobulin-producing cell called the plasma cell, which persists
for several weeks in circulation. The other is the long-lived memory B
cell.

37. What is the evidence that certain DNA rearrangements are preferred
during the generation of virgin B lymphocytes?

Individual mice of certain strains produce virtually identical
antibodies (many with identical and specific N regions) against
specific haptens, indicating that specific gene configurations are
preferred during the antigen-independent stage of B lymphocyte
development.

38. What is the key difference between the reaction of antigens with
antibodies, and reaction of antigens with the T-cell receptor?

Antigen reaction with the T-cell receptor always occurs at the cell
surface; the T-cell receptor is always membrane-bound.  Antigen
reaction with antibodies can occur at the cell surface, but usually
occurs in solution. Antibodies can be either membrane-bound or
soluble.

39. T cell education in the thymus results in the death of 95% of the
newborn T cells.  This is accomplished by both positive selection and
negative selection.  Explain the difference between these two
selective mechanisms.

Positive selection occurs when the T-cell receptor of a new T cell
does not interact with either class I or class II MHC molecules of
that particular animal. Negative selection occurs when the T-cell
receptor reacts with a class I or class II MHC molecule containing a
self peptide.

40. Immunoglobulin genes undergo somatic mutation after activation and
proliferation of B cells. T-cell receptor genes are fixed; i.e., they
do not undergo somatic mutation after activation and proliferation of
T cells. Why?

Changes in the specificity of the T-cell receptor could lead to
self-reactivity and autoimmune reactions.

41. What are two roles for macrophages in protecting vertebrates from
infection by bacteria?

Macrophages function in antigen presentation to T cells and in
phagocytosis of bacterial cells.

42. What molecular mechanisms are known to operate in the generation
of antibody diversity?

The diversity of antibodies results from DNA breakage and
recombination, use of alternative polyadenylation sites in processing
of pre-mRNAs, somatic mutation, and addition of random bases by
terminal transferase.

43. Why are children generally much more susceptible to infection than
are adults?

When children are first exposed to a particular pathogen, they can
mount only a weak primary immune response, which generally cannot
prevent infection. In contrast, adults have many memory T cells and B
cells resulting from previous exposure to many different pathogens.
Because these cells can respond quickly to a pathogen, adults
generally are less susceptible to infection than children. However,
adults are just as susceptible as children to infection by pathogens
to which they have not been previously exposed.

44. What is the evidence that tolerance (inability to react with
self-antigens) develops early in the life cycle of vertebrates?

A foreign antigen that has been introduced into a newborn mouse will
not elicit an immune response in that mouse when reintroduced after
the mouse is mature. However, when the same antigen is administered to
an immunologically naive mature mouse, it will produce a normal immune
response.

45. A B cell that produces IgG cannot switch to production of IgM, but
an IgM-producing cell can switch to production of IgG. Why?

A shift in the class of immunoglobulin produced by a B cell and its
progeny -- called class switching -- occurs by recombination between
the VDJ region and the downstream constant regions specific for each
class in heavy-chain DNA. The constant region for the chain (C) lies
upstream of the constant regions for all the other heavy chains,
including C. Thus an IgM-producing B cell can switch to production of
any of the other immunoglobulin classes. However, a cell producing IgG
cannot switch to IgM production because its DNA has previously
undergone a switch recombination event that eliminated the C region.
See Figure 27-40 in MCB.

46. Why does only one of every three V-J joints result in production
of a light chain?

During the recombinations joining the V and J regions in light-chain
DNA, a few nucleotides are randomly lost. Because of this random loss
of nucleotides, the resulting V-J joint may maintain the original
reading frame (i.e., be in phase) or it may change the reading frame
(i.e., be out of phase) and generate stop codons downstream in the VJ
unit. Since the DNA coding sequence is read in groups of three
nucleotides, these random recombinations result in two nonproductive,
out-of-phase joints for each productive, in-phase joint. See Figure
27-25 in MCB.

47. What is the evidence that cytotoxic T lymphocytes (CTLs) must
recognize both a foreign antigen and a class I MHC gene product before
initiation of a cytolytic response?

CTLs from a mouse that has been infected with a virus will kill
virally infected cells from an identical (syngeneic) mouse, but will
not kill virally infected cells from an otherwise identical mouse that
differs only in the MHC region of the genome.


---

Thanks in advance
Dave

-- 
Dave Rintoul                 Internet: drintoul at ksu.ksu.edu
Biology Division - KSU     Latitude 39.18, Longitude -96.34
Manhattan KS 66506-4901                Compuserve: 71634,32
(913)-532-6663 or 5832                  FAX: (913)-532-6653



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