[* Due date: Those in by 11/18 will be
guaranteed feedback by 12/9. Those in after 11/18 will be
processed as time allows. A 10-point/day penalty will be
assessed, including weekend days. None will be accepted
after Thanksgiving.] To begin your search, you may want to check out the
library's database section. You may want to use Elsevier's
Science Direct, Wiley Interscience, and Dialog's Biosis. If
you want to just jump in, try PubMed: In addition to the sites above, check out additional
links on the Links
page. [Let me know if you find useful sites which should
be added.] You can save your selected search results in a log, as
you did for the earlier computer exercises. This is handy
for making a useful printed short list to take to the
library, or for use when in other databases, accessing
on-line journals, or requesting interlibrary copies. Some questions are general enough to allow you latitude
in your searches; others are specific and allow fewer
options in obtaining your information. All tools for doing
literature searches are open to you. If you don't know how
to approach a particular question, see me. THE HONOR
SYSTEM DOES APPLY. The point of this exercise is, in
part, to learn how to do a literature search. So- do your
own search. Carpooling for library field-trips for
journal access, or sharing information on database use or on
finding on-line journals, is certainly acceptable. You have several choices in getting the actual papers.
[Remember the first computer exercise?] You can use
our library and other libraries, such as UCD and UCSF. You
can access some on-line journals for free, some on-line
journals have limited access, and some charge a fee. PubMed
is now providing direct links to journals on-line, and the
free ones are marked. In addition, our library is part of
some consortia which allow us access to specific journals.
Particularly useful are Elsevier and Wiley Interscience.
Other resources for free access are NewJour [linked on
the library's Journal & Database page] and Highwire
Press: www.highwire.org.
You can request documents at the library from journals not
available locally or free electronically. You can order
papers on-line, but this is usually the most expensive
solution, if you have a significant list of articles. When
in a real, not virtual, library, be kind- don't make other
people's searches a royal pain- there is plenty of space for
all. Replace references on the central re-file shelves for
journals when you are finished with a volume. That way
others may locate them more easily. Citations of your references are required, unless
otherwise stated. (Be precise! You can count on us looking
up some of these. Try copy/pasting from your log to avoid
typos.) An example of a reference citation is as
follows: Group your reference citations for each question with
your answers to that question. They may precede or follow
your answers as you choose, but they MUST BE PRECISE. A
general bibliography without citation notes within your
answers is not acceptable. Use either a number or the first
author, and year if necessary, within your answer to refer
to your references. Papers are to be typed in a standard font style
[please avoid script styles]; 12 pt is preferred, 10
pt is tolerated. Clearly indicate which questions are being
answered and collate them in order. [E.g.: question 1
before question 3; a before b.] Check to be sure all
subsections are answered and all parts of questions are
answered, or points will be lost. Page limit: 12, including
answers and citations. Please- no report covers or binders.
[Saves you $$ & saves us time.] Just a single
staple in the upper left-hand corner will do fine. [NO
paperclips!] Although most would assume that a statement on plagiarism
is neither required nor needed, I unfortunately discovered
otherwise. I direct you attention to the University's
catalogue for campus policy on plagiarism. I expect answers
in your own words, not that of the journals cited, or others
not cited. I expect some thought and synthesis of
information, not a regurgitation of phrases quoted. Quotes
are permissible in appropriate circumstances and when
referenced, but they should be used sparingly, if at all.
Use your log appropriately. You can use it to collect papers
and references. It is one useful way of organizing citation
lists, which can then be copied to your paper chase file.
But don't use it as a source of transferred blocks of text
into your answers. If I find an answer is plagiarized, it
will receive NO CREDIT. For help on this, check out the
following: http://www.indiana.edu/~wts/wts/plagiarism.html If you find writing a problem, or you have difficulty
organizing notes into coherent text, the Writing
Center can be a lifesaver. They are very good at cutting
to the chase of what the problem is and offering workable
solutions in a minimum of time. [But don’t wait
until the last minute.] PART A. Choose either question 1 or 2 below. [30
pt] 1. Intercellular collaborations resulting in cell
signaling are a necessary part of any immune response. Cells
need to interact with each other in specific ways, including
direct contact through membrane-bound receptor-ligand
interactions and/or soluble signal molecules, such as
hormones and cytokines. Initial events in cell signaling
lead to signal transduction, which as a term, includes
events beginning with receipt of signal at the cell surface
by whatever means, through intracellular signal pathways and
second messengers, to affecting a response via gene
activation and expression. a.
Integrins are an important group of adhesion
molecules involved during cell migration and homing to
specific tissues. Timothy Springer has been studying the
cell signaling events associated with integrin binding and
the specific molecular mechanisms involved. Describe briefly
the methods used in his laboratory to investigate the
functional and structural aspects of integrins during
adhesion events. Summarize what has been discovered to date
in terms of molecular conformational changes of integrins
during adhesion and their role in cell signaling. b. Jason Cyster is interested in chemokines and
receptor-ligand interactions involved in lymphocyte homing
in splenic white pulp, peripheral lymph nodes, and Peyer's
patches. Describe what is understood about chemokine
receptor signaling in B cell homing. c. Phosphoinositide 3-kinases are involved in
chemotaxis of both neutrophils and lymphocytes. Summarize
what is understood to this point about the role and function
of phosphoinositide 3-kinases. 2. Multiple pathways are involved in lymphocyte
development in primary lymphoid tissues, including
commitment toward B-cell or T-cell lineage and
immunoglobulin or T-cell receptor rearrangement. During
these processes, cells undergo both negative and positive
selection prior to the release of virgin lymphocytes to the
secondary lymphoid organs and tissues. a. Ana Cumano
investigates early lymphocyte development in fetal liver,
bone marrow, and thymus. She is involved in
elucidating the different requirements and pathways found in
these tissues relating to B cell and T cell maturation.
Describe briefly the methods used to examine the
immunoglobulin heavy chain rearrangements in cells located
in the fetal live and bone marrow. Summarize the
significance of her findings. b. E2A gene products are involved in both B cell and
thymocyte development. Cornelius Murre is interested in the
regulation and function of these helix-loop-helix proteins.
Describe what is known about the role of these E-proteins in
development of both B cell and T cell lineages. c. What is Notch-1? How is it involved in signaling
during lymphocyte development and what is its
significance? B. Choose either question 3 or 4 below. [40
pt] 3. There are many molecular mediators involved in
host defense, both as innate responses to pathogenic
challenges and in concert with adaptive immune responses.
The following questions focus on only a few key areas of
research. a. Tumor
necrosis factor [TNF] is a member of a large
superfamily of proteins. Summarize the range of functions
found for members of the TNF superfamily. Choose one of
interest to you and describe the latest understanding of its
mechanism of action and the specific role(s) ascribed to
it. b. The receptors for TNF ligands and co-receptors
also make up another superfamily of proteins. CD40 is one
such protein and appears to be involved in apoptosis and in
the development of memory B cells rather than plasma cells.
Describe what is known about CD40 and the mechanisms behind
its involvement in cell death on one hand and generation of
memory cells on the other. c. Type I interferons, IFN-a
and IFN-b, are well known as
antiviral mediators. They are also involved in other types
of activity, including innate response to non-viral
pathogens. Summarize the recent understandings of
their role in non-viral responses and the mechanism of their
functions. d. Anti-microbial peptides are a diverse group of
small molecules found widely in nature, including outside of
the animal kingdom. They are significant in innate immunity.
Cite a specific example and describe its mode of action and
potential for use as a therapeutic agent in controlling
infectious diseases. 4. The "War on Cancer" was declared during the
Vietnam War, with statements proclaiming that a cure for
cancer would be found within five years. The Vietnam War has
been over for a long time, yet the fight against cancer
rages on. The more we understand about immune responses and
the mechanisms involved, the more we understand why the
fight against cancer is so difficult. a. T cell
responses, particularly CTLs, are critical in the control of
tumors. Many strategies have been explored to expand these
responses. Novel vaccines have been developed against
identified tumor antigens: however, these same antigens are
often normal self-proteins being expressed on other types of
cells. Cite a specific example of a tumor antigen that has
been found to be a normal protein. What are the consequences
when this antigen is used as a vaccine, both in terms of
tumor control and in terms of side effects? b. Although the focus has long been on MHC class
I-restricted T cell responses, newer evidence is showing the
importance of MHC class II-restricted antigen recognition.
Briefly summarize the significance of processing exogenous
antigen by CD4+ T cells and the relation to tumor responses.
Discuss how this information could be used to develop
improved treatments for tumors. c. It has been found that low-avidity self-specific T
cells survive the negative selection process in the thymus
and normally do not proliferate. These cells have been
linked to the development of autoimmune diseases; however,
they are also attracting attention in terms of exploitation
for anti-tumor therapies. Summarize the findings on these
cells and their potential role in controlling tumors. After
weighing the benefits and risks, what is your opinion about
the efficacy of using this approach? d. Antibodies are also produced in response to
tumors. Describe a specific example of an immunoconjugate
[antibody + toxin or other effecter molecule] and
how it can used to augment treatments against some tumors.
What is the current thinking about the utility of this type
of approach? C. Design a question. [30 points] You write a
question concerning an area of your interest. I review it,
making comments or adding/subtracting parts or whatever.
Then you do the search to answer your question. I am frequently asked if the paper chosen for journal
discussion can be connected to this part of the Paper Chase.
In short- yes. [Can they be unrelated?
Certainly.] a. The
question. Turn in by 10/14. I will return it by 10/19. b. The answer. Due on 11/18 along with the rest of
the answers. NOTE: Be sure to include your original
question, along with written comments,with your answers.
[Don't assume I'll remember everything about your
question out of the blue.]
INTRODUCTION
Thatcher,
E.F. and Gershwin, L.J., 1989. Colostral transfer of
bovine immunoglobulin E and dynamics of serum IgE in
calves. Veterinary Immunology and Immunopathology
20:325-334.
THE QUESTIONS
YOUR QUESTION
Updated 10/4/04 by thatcher@sonoma.edu