Guidelines (To earn the maximum number of points, carefully read and follow directions):

1. Answer any four of the five questions below. Each question is worth 25 points. Be sure you address all the questions within each question.
2. CITATIONS: You are expected use other resources, such as original journal articles and review articles, to answer these questions. Use only recent resources, preferably 2015 or later.
You must include a list of references at the end of your exam. Citations must be formatted similar to those on the Zuo et al, JCI insight article. That is, appropriate citations must appear within your narratives and at the very end of your submission. [Points will be deducted for missing citations or list of references.] Citations in the natural sciences are very different from those in the humanities; in science, you are citing ideas and the main theses rather than taking the text verbatim (never use direct quotes). Read, understand, synthesize, and rewrite in your own words.
3. In your answers, be as specific and as concise as possible. Draw your own diagrams if they can help you explain your answers. However, be sure the diagrams can stand alone, meaning that without reading the text, one must be able to get a general idea of what the figure is communicating. It is essential, then, that each diagram is accompanied by a figure caption and that everything is carefully labeled. Be sure to cite the source(s) of your diagram.
4. The format for each answer should be in the form of a condensed research paper. Each answer should be 1-2 pages (no more than 2 pages), 12-font size, reasonable margins, and single- to 1.5-spaced. Be concise and to the point. Less is more.

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1. Listeria monocytogenes are bacteria with unique features that when they are phagocytosed, they express pore-forming toxin listeriolysin O (LLO) to perforate phagosomes and gain entry into the cytosol of phagocytic cells. Researchers have taken advantage of this feature to engineer L. monocytogenes as a vector for cancer therapy. What is the logic behind this? Explain the specific antigen processing and presentation processes and effector T cells that are elicited for typical L. monocytogenes infection and for the killing of cancer cells.

2. What does it mean that an individual with the specific HLA-B*46:01 allele has increased susceptibility to SARS-CoV2 infection? Explain the protein structure of the peptide binding groove encoded by HLA-B. Describe how peptides are anchored in its groove and the general implications of why having certain HLA alleles may yield increased susceptibility to certain diseases.

3. Lymphoplasmacytic lymphoma (LPL) is the result of t(9;14)(p13;q32) (PAX5; IGH) chromosomal translocation. Explain the molecular mechanism that resulted in this translocation. What may have occurred at the DNA level? Explain how this was able to cause the onset of cancer. How does this particular tumor reflect the developmental and differentiation state of the B cells?

4. The Wiskott-Aldrich syndrome is an immunodeficiency syndrome caused by a defect in the WAS gene which encodes a protein that facilitates the polymerization of actin cytoskeleton. How is actin polymerization important for T cell activation and effector T cell function that missing the WAS protein (WASp) results in an immunodeficiency? What specific intracellular signals are required to activate WASp and ultimately actin polymerization from the initial T cell receptor engagement?

5. Define allelic exclusion. What cellular signals and molecular processes at the DNA level are involved in establishing allelic exclusion? Be specific. Why is allelic exclusion more important for the B cell receptor but not as much for the T cell receptor?

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