Man hat die Wohnung heute eingerichtet.

Tetramer Technology (Zhang) Tetramer technology has been widely used in T cell-based research. (A)  Please briefly describe the tetramer technology and how it works.  (2 points) (B)  We have discussed CD8+ T cells (using OT-1 T cells as an example), gamma-delta T cells, iNKT cells and MAIT cells.  Based on our discussion related to these cell types, please list MHC I family member/antigen pair that can be used for tetramer construction for three of the above cell types.  (1.5 points) (C)  Briefly describe which cell type above is not the optimal cell type to use for tetramer technology, and why.  (1.5 points)

CD8+ T Cells (Zhang) (A)  CD8+ T cells in circulation enter lymph nodes by crossing the walls of high endothelial venules (HEVs).  Briefly describe the major events of CD8+ T cells entry into lymph nodes, focusing on adhesion molecules, chemokines and receptors.  (3 points) (B)  Please list the major signaling events from antigen presenting cells (APC) for full activation of CD8+ T cells.  (1.5 points) (C)  In the case of weak co-stimulation, full activation of CD8+ T cells needs the help from CD4+ T helper cells.  Briefly describe the process of how CD4+ T cells educate APCs for the full activation of CD8+ T cells.  (1.5 points) Solid cancers are heterogeneous, containing some cancer cells with normal MHC I expression and some cancer cells with very low MHC I expression.   You engineer chimeric antigen receptor CD8 T cells (CAR-T) to target a tumor neoantigen in a patient’s breast cancer.  Although the CAR-T cells very efficiently kill cancer cells expressing MHC-1/antigen complex, a much higher CAR-T/cancer cell ratio is required to kill MHC-1/antigen-negative cancer cells. (D)  Please briefly describe the major effector molecules for efficient killing of cancer cells expressing MHC-1/antigen complex.  (3 points) (E)  Please name an effector molecule involved in the non-efficient killing of cancer cells that are negative for MHC-1/antigen expression.  (1 point)

Sepsis (Jin) Sepsis is a major public health issue, contributing to one in three hospital deaths in the US.  Endotoxin (also known as lipopolysaccharide) is the most potent trigger of the severe inflammatory response that leads to sepsis and septic shock.  Bruce Beutler won the 2011 Nobel Prize for the discovery of the LPS receptor TLR4.  However, inhibiting TLR4 signaling fails to improve sepsis outcomes in large human trials.  Please postulate a hypothesis to explain why inhibiting the LPS-TLR4 pathway had no effect on sepsis in humans.

T Cell Development (Brusko) (A)  The thymus is divided into the cortical and medullary regions.  Specialized stromal cells within each region are key mediators in thymic selection.  Name these cell types and explain the process they mediate. Give specifics about the MHC expression of the stromal cell and the resulting surface expression of the thymocyte.  (4 points) (B)  More than 90% of thymocytes express the alpha-beta TCR, while only 10% express the gamma-delta TCR.  At what phase in thymocyte development are gamma-delta T cells produced, and what is unique about their developmental process?  (4 points)

T Helper Cells and Their Roles (Brusko) (A)  Naïve T cells follow a highly predictable program in response to TCR stimulus and costimulation provided in vitro.  Identify a molecular and/or cellular feature at three key points along this activation program – within hours, at 1-day post activation, and at several days post activation – that you would use to identify the T cell response to stimulus.  (4 points) (B)  Name the 4 major T helper subsets and an effector cytokine they produce.  (4 points) (C)  Briefly describe an example of T cell plasticity and explain why this phenomenon provides an advantage.  (2 points)

Somatic Diversification (Moser) Affinity maturation is a process induced by T-dependent antigens in germinal centers that increases the strength of antibody binding to antigen. (A)  Briefly describe the steps involved in the process that ensure that B cells with higher affinity for antigen emerge.   (4 points) (B)  Activation induced cytidine deaminase (AID) is the enzyme that facilitates both Class Switching and Somatic Hypermutation in activated B cells.  For class switch recombination, which immunoglobulin chain(s) and region does AID target?  (2 points)

This is a 16 week course.

This is an online course

The upper receiving chamber of the heart is the