NAME_____________________________________________________________TA__________________ SEC____17.012 Problem Set 5 FRIDAY October 29, 2004Due to popular demand, and a congenial staff due to the recent performance of theRed Sox, this Problem set upon completion must be inserted into the box Problem sets will NOT be accepted late. Solutions will be posted on the web. Question 1Viruses have evolved several mechanisms to evade recognition and elimination by theimmune system. Our immune systems have likewise evolved ways to counteract thesemethods of evasion.a) What type(s) of cells of the immune system recognize virally infected cells?KILLER T cells!… otherwise known as Cytotoxic T lymphocytes (CTLs)b) How do these cells do so? Explain briefly.The Killer T cell receptors (TCRs) bind specifically to viral protein epitopes presented on MHC class Imolecules. The killer specific T cell upon recognition of this epitope/MHC I complex, secretes perforinwhich perforates or makes a hole in the infected cell, killing it.c) Besides viruses “hiding-out” from most of the immune system within cells, how might viruses furtherprohibit the previously mentioned immune cells from identifying them in host cells? **Hint, our immunesystem has retaliated to this evasion technique with special immune cells called natural killer cells (NK cellsfor short). These NK cells recognize and kill cells that have low or no MHC class I expression at theirsurface.Viruses can block MHC I presentation at surface of host cells, or block transport, or downregulate MHC I so that the cell does not present antigens.It turns out NK cell activity is a little more sophisticated. NK cells do not kill cells that have MHC Ireceptors on their surface. Cells without MHC I receptors on their surface are candidates for killing by NKcells. But NK cells also need to be activated for killing by specific receptors on the target cell's surface.d) Knowing more about how NK cells function, suggest a way in which the virus may now evade NK cellrecognition and thus avoid its subsequent demise.Viruses downregulate expression of host cell's specific activating receptors or prevent surfaceexpression/transport. Or block downstream modulators of activator signals.e) In addition, all cells have mechanisms to protect themselves from double stranded RNA (dsRNA) viruses.What is this innate mechanism of protection? Briefly explain how it works.Answer obtained from WWW. The interferon + response: -blocks translation, -endonucleases, degradeRNA or can lead to apoptosis or death of the cell before the virus has a chance to replicate. Can renderadjacent cells resistant to infection. “Interferons are protein components of animal cells which are synthesized and excreted under avariety of stimuli and make other cells of the same species incapable of replicating virus”.DeSomer and Cocito 1968MIT Biology Department7.012: Introductory Biology - Fall 2004Instructors: Professor Eric Lander, Professor Robert A. Weinberg, Dr. Claudette GardelMIT Biology Department7.012: Introductory Biology - Fall 200Instructors: Professor Eric Lander, Professor Robert A. Weinberg, Dr. Claudette Gardel2Question 2As a UROP in the Weinberg lab, one of your duties is to take care of the mice used forexperimentation. During your tenure in the mouse facilities you notice a colony of micethat is highly susceptible to bacterial infections. In order to figure out why, you firsttake a blood sample and look at the levels of serum proteins. You are shocked to findthat these mice lack antibodies in their serum! You are now aware of why they are sosusceptible to infection.a) What cell type do you suspect is affected by this mutation? Plasma cells.With what little spare time you have from your lab duties and school work, you decide totry to figure out why there are no antibodies circulating in these mice. You find that themutation that leads to the disease is within the immunoglobulin heavy chain locus.Sequencing the locus reveals that the mutation is a deletion of the C-terminaltransmembrane domain of the heavy chain. You’re not an immunologist and frankly youwere kind of surprised to learn that the antibody heavy chain has a transmembranedomain, afterall you always have been taught simply that antibodies are secreted.However, based on your knowledge of cell signaling that you learned in 7.012, you begin tothink of the antibody as a receptor and thus can make sense of why it has atransmembrane domain.b) How does the transmembrane domain of the antibody enable the cell to signal from an“antibody receptor” to the nucleus? (Answer by comparing the alternative possibility inwhich the antibody is just secreted.)'Antibody receptor' bridges antibody binding to cell stimulatory, mitogenic signaling. Ifantibodies were only secreted there wuld be no way for a cell to 'know' that the antibody(Ab) recognized and bound Antigen (Ag) and signal this information directly.c) Why might this signalling be important for antibody selection prior to secretion fromthe cell?Membrane bound antibodies that bind antigen very well could stimulate their cells togrow/expand (clonally expand –with of course further stimulation of a helper T cell).Antibodies expressed on cells that don't bind antigen well would lack mitogenic signals.d) Now hypothesize why these mutant mice lack antibodies in their circulation?Without being able to receive positive mitogenic signals, these cells do not get the signalto clonally expand, and thus differientate into plasma cells which secrete antibodies.3Question 3Note that the 2nd bacterial infection in the figure above would have had to be an infection withexactly the same kind of bacterium as the first infection. For instance, a Bordatella pertussis(whooping cough) infection followed by a second Bordatella infection at a later time point. ABordetella infection followed by a different bacterial infection, for instance, Bacillus anthracis(anthrax) would show a different graph.The diagram above depicts a typical antibody response to a primary and secondarybacterial infection in wildtype mice. Being that it is the week following Halloween and youhave an abundance of candy, you decide to feed your mice some of the “more suspect”candy that you got from some creepy old ladies whom you think may have tricked ratherthan treated. Indeed, after putting the mice on the candy diet you find that theirantibody response has changed! It now looks like this…You
View Full Document
Unlocking...