Bob's Fall schedule had been a killer, so he planned a Thanksgiving break in the White Mountains. On his first morning there, he awoke with a fever, felt tired and achy, and had a cough but no sore throat. After several days of feeling terrible, Bob went to his HMO and was diagnosed with influenza virus (flu).
Influenza virus is spread through aerosols (tiny droplets in the air) and infects epithelial cells lining the upper respiratory tract. The virus binds to the host cell surface glycoproteins and enters the cell , where it uses host ribosomes and enzymes (modified by viral proteins) to make thousands of copies of itself. The new virions bud from the host plasma membrane at sites containing virus proteins; the membrane becomes the viral envelope.
The virus has an RNA genome made up of 8 pieces of RNA associated with nucleoprotein (NP). The genome is surrounded by a matrix protein underlying the lipid bilayer envelope acquired as the virus buds from the host cell plasma membrane. See left-hand figure below: purple squiggles are the RNA, green circles are the matrix protein, dark pink line is the lipid envelope, and purple trapezoids are the envelope glycoprotein "spikes".
The virus mutates easily, and different antigenic types of influenza usually appear each flu season. Influenza virus has two envelope (surface) glycoproteins by which different variants are characterized. One is hemagglutinin (H = HA, shown all in purple below left), which is the molecule that allows influenza to bind to and infect its host cells by binding its receptor site to the host cell glycoproteins. The second is neuraminidase (N = NA, shown as purple with pink boxes), which helps the newly formed virus particles leave the host cells to infect new cells. Influenza viruses are categorized by H and N into two major groups, Influenza A and Influenza B, and into many antigenic types within each group (examples: H1N1, H2N1, H3N2, etc.). Influenza A usually causes a more serious disease than Influenza B.
Influenza virus structure (left) and details of hemagglutinin (H) structure.
1. List from the information above the antigens on Influenza and what kind of molecules they are (chemically). Contrast the antigens "seen" by B cells and those "seen" by T cells. How is it that influenza can change its antigens and still bind to and infect human epithelial cells?
2. Compare and contrast the structure of TCR and BCR (membrane Ig) molecules on T and B cells.
3. What kinds of T cells would respond to Influenza virus? How do they differ in how they "see" influenza antigens?
4. How do infected epithelial cells process and present influenza antigen to cytotoxic T cells? Describe the process beginning with virus H protein in the infected cell cytoplasm, and discuss all the molecules required to make peptides and get them onto MHC and out on the infected cell plasma membrane. Name the human MHC molecules which can present H peptide on infected cells to cytotoxic T cells.
5. How do antigen-presenting cells process and present influenza antigen to helper T cells? Describe the process beginning with virus H protein in the infected cell cytoplasm, and discuss all the molecules required to make peptides and get them onto MHC and out on the antigen-presenting cell plasma membrane. Name the human MHC molecules which can present H peptide on antigen presenting cells to helper T cells.
6. Infected epithelial cells have H protein in their plasma membranes (which will become part of the virus envelope) and H peptide on MHC (which will be recognized by cytotoxic T cells. To which of these can antibody bind? What will be the consequences of antibody binding to infected epithelial cells (will this activate any immune system effector functions)?
7. Describe the genes for alpha and beta chains in the mature naïve T cell which is waiting in the mucosal lymphoid tissue (MALT) to recognize and respond to Influenza HA. Explain which gene segments encode the variable and constant parts of the alpha and beta chains.
8. Explain how only non self-specific T cells with functional TCR (able to bind self MHC Class I or Class II) emerge from the thymus.
Answer the questions with as much detail as possible and save as a Word document entitled YourNameCase4.doc. Send to jdecker@u.arizona.edu as an attachment by 9 AM Thursday June 19. Make sure your name is in the document as well as in the title.
Supplementary Materials: Antigen, MHC, TCR, T Cell Development