MCDB 1030 Hour Exam 2 April 7, 2005 150 points Good luck! Please write legibly! Some common mis-conceptions/confusions: The words antigen, pathogen, and antibiotic mean different things – be sure you have them straight. Antibiotics are used to treat bacterial infections, not viral infections. Be sure you are clear on the distinctions between bacteria and viruses, and know which of the diseases we talked about are caused by which type of pathogen. 1. (14 points) Explain why both cellular and humoral immunity are important for fighting a viral infection. Cellular immunity is important because cytotoxic T cells can kill infected cells, thus preventing further production of virus particles. Humoral immunity is important because antibodies can bind to the protein spikes on viral particles that mediate attachment to host cells and thereby prevent infection of additional cells. 2. (8 points) Explain the role of interferon in the response to viral infection. Interferon is a protein released by infected cells. It is taken up by neighboring cells and causes those cells to synthesize antiviral proteins (in an inactive form). If those cells become infected, the antiviral proteins will be activated and will prevent viral reproduction. 3. (16 points) Suppose a human is infected simultaneously with a H5N1 avian influenza virus and an H3N2 human virus. a) What types of viruses might emerge? b) Why might this cause a problem? c) What unusual characteristic of the influenza virus would be responsible for the production of the viral types you listed in a? a) (4 points) H5N1, H3N2, H5N2, and H3N1 b) (6 points) This might lead to the production of a virus with the lethality of the avian H5N1 virus (>70%) and the ability to spread easily from person to person, like the human H3N2. c) (6 points) The segmented genome of influenza allows the reassortment of genes from two different viruses that co-infect a cell, leading to the production of hybrid viruses that have various combinations of the genes of the two infecting viruses. 4. (14 points) Explain why proper macrophage function is important for both the second and third lines of defense against a bacterial infection. Macrophages play an important role in the second line of defense by ingesting and killing bacteria. They play a role in the third line of defense by displaying antigens from the digested pathogens on the surface of MHC-II molecules in order to activate the acquired immune response. 5. (16 points) Explain the different roles of MHC-1 and MHC-2, and explain why it is important that humans have both types of molecules. (8 points) MHC-1 molecules are found on the surface of all nucleated cells, and are used to display antigens derived from an intracellular pathogen. MHC-2 molecules are found on the surface of antigen presenting cells and B cells, and are used to present antigens to T helper cells in order to activate the acquired immune response. (8 points) It is important that humans have both types of molecules because antigen displayed on the surface of MHC-1 is a signal that the cell should be killed, whereas antigen displayed on the surface of MHC-2 is a signal that activates the immune response. It is important that macrophages and B cells not be killed because they need to go on doing their jobs. 6. (16 points) What do the following enzymes do? In each case, indicate the type of organism in which the enzyme is required. (For viruses, specify the type of virus.) a) RNA-dependent DNA polymerase copies RNA and synthesizes DNA (required in retroviruses) b) RNA-dependent RNA polymerase copies RNA and synthesizes RNA (required in RNA viruses) c) DNA-dependent DNA polymerase copies DNA and synthesizes DNA (involved in replication in cells and in DNA viruses) d) DNA-dependent RNA polymerase copies DNA and synthesizes RNA (involved in transcription in bacteria, eukaryotes, and DNA viruses) 7. (16 points) a) (6 points) What are the three toxins produced by Bacillus anthracis, the causative agent of anthrax? PA (protective antigen), LF (lethal factor), and EF (edema factor) b) (10 points) Explain why the individual toxins do not cause problems, but the combination does. LF and EF cause problems in the cytoplasm of cells by interfering with cell signaling mechanisms. These toxins can only get into cells by combining with a heptamer of PA that is bound to target cells. Thus they are harmless individually. PA itself has no toxic effects – it is simply the shuttle for LF and EF. 8. (14 points) What is the mode of action of penicillin and the related beta-lactam antibiotics? How does resistance arise? Penicillin interferes with the enzyme that cross-links peptidoglycan, leading to a weakened cell wall. Resistance involves an enzyme, b-lactamase, that destroys the blactam ring of penicillin and makes it inactive. 9. (14 points) What is “infectious dose”? What is the most important factor that determines the infectious dose? (6 points) Infectious dose is the number of pathogens that are required to start an infection. (8 points) The most important factor that determines infectious dose is the mode of entry. Low infectious doses are typical for pathogens that enter through a break in the skin or are injected into the bloodstream. High infectious doses are typical of pathogens that are ingested and must survive the harsh conditions of the stomach and intestine. 10. (18 points) Explain why being highly virulent is an effective strategy for plague and anthrax, but not for the rhinovirus that causes the common cold. (6 points for each explanation) Being highly virulent is an effective strategy for plague because it is a vector-borne disease, and an immobilized human is more likely to be bitten by a flea. Anthrax has to be highly virulent because it can only spread to a new host if the animal dies and releases blood into the environment. The bacteria will then form spores that are stable in the environment for a very long period of time and can wait until a new host comes along. Rhinovirus spreads via coughing and sneezing, and requires direct human-to-human transmission. If it were terribly virulent, infected people would be bed-ridden and wouldn’t have the opportunity to expose lots of new hosts, as they typically do when they go to work or school while infected with the rhinovirus.