1. Little Efram is highly susceptible to skin infections. You suspect that he has a problem with his defensins. Tell him about defensins-- what they do, how they work, etc. (5 pts) What could you do (if you had a laboratory) to test if defensins are truly missing on the Efram's skin? (2 pts)
Defensins are antimicrobial peptides that are located in the skin (dry surfaces, beta type) and in the gut, in intestinal crypts and paneth cells. They are also secreted by mast cells, neutrophiles and eosinophils (mucosal sites, alpha type). We make more defensins when the skin is broken. Defensins defend us by bonding to the negatively charged phospholipids that occur in the cell walls/membranes of bacteria. Bacteria have a hard time evolving a way to avoid them, because it's not easy to change your membrane, and so die.
In addition to the essential protective function, defensins also promote epithelial growth via angiogenesis, activate TLR (toll receptors) on mast cells, neutrophils and dendritic cells, and generate chemokines that signal other helping cells to come to the site.
When you don't have strong defensins you have a hard time keeping the bacteria from bothering your skin and gut mucosa. You can get atopic dermatitis, eczema, Crohn's disease and more.
Efram's mom read about a new therapy where the mother can rub saliva all over the skin infection to help it to heal. Why might that help? (3 pts)
There is lysozyme in saliva. It's an enzyme that digests bacteria.
2. A recent paper states that "TLR2 likely contributes to increased circulating TNF-alpha and sTNF receptor (TNFR) levels in cirrhosis." Draw a picture (with a cell) that illustrates this pathway. (2 pts) What is a TLR and what sorts of things do the TLRs bind? (2 pts) What is TNFα and what does it do? (2 pts)
TLR2 is a toll receptor so it would have to be on an m/, DC or neutrophil. The TLR "danger" signal activates T cells, and probably does so via releasing IL-12 since that starts the Th1 response which results in TNF-alpha as well as IFNgamma, IL2 and GM-CSF. I don't know what sTNF or TNFR are. Cirrhosis is usually referring to the liver but can't other organs be cirrhotic?
Cirrhosis patients can be treated with antioxidants such as alpha lipoic acid 200 mg/day orally; N-acetylcysteine 1800 mg/day i.v. or carboxycysteine-lysine salt 2.7 g/day orally; amifostine 375 mg/day i.v.; reduced glutathione 600 mg/day i.v.; and a combination of vitamin A 30,000 IU/day orally, vitamin E 70 mg/day orally, and vitamin C 500 mg/day orally. The antioxidant treatment should be administered for at least 10 consecutive days. What would you expect antioxidants to do? (2 pts) The antioxidant treatment also reduces the serum levels of IL-6 and TNF-alpha. Why would this be good for cirrhosis patients? (2 pts)
We must be talking liver, still. Vitamin E, cysteine, amifostine and glutaothiona, vitamin A and E and C. Ten days. I would guess all these antioxidants would counter the free radicals that are throughout the body due to ROS (reactive oxygen species) run amok. This person, who has a cirrhotic liver, probably has a lot of ROS because he probably drinks alcohol and probably has reduced liver function, adding up to a substantial toxic burden. Reducing IL6 and TNFalpha would be reducing the signals that lead to acute inflammation, which would allow inflamed tissues to calm down, perhaps heal a little.
3. B cells secrete antibodies and have antibodies on their surface. Draw an antibody, including the heavy and light chains. Draw arrows to designate: the variable region, the Fc region, the part of the antibody formed by VDJ recobmination, the class switching area, and circle the part that makes the antibody specific. (6 pts) What is the order of class switching? (2 pts)
This one I can do. Even in words. Antibody is shaped like a Y with longer, heavy chains on the inside, and light, short chains on the outside of the "arms". The arms are the variable or FAB region and are the part formed by VDJ recombination. The very tips of the arms, or the hands, are the part that makes the antibody specific for a certain antigen. The class switching area is the bottom half of the Y, aka the constant region. The classes in order are M, D, G, E, A. The Fc region is the very bottom of the Y, the bit of the antibody that binds to the FcReceptor on a neutrophil, macrophage, dendritic cell or B cell. The constant region is held together by two disulfide bonds.
Recently, a company in china successfully cloned 3 human embryos. Would these clones have identical antibodies? Explain why or why not. (2 pts)
Clones would have identical MHC's, but not identical antibodies, unless they were exposed to exactly the same antigens. They will have antibodies that reflect exactly which germs manage to get in their bodies, which can be different even if they are lying side by side in a crib.
4. Charlie is two years old and has croup. His parents suspect that he has Respiratory Synsytial Virus (RSV). RSV is the primary cause of hospitalization in the first year of life for children in most parts of the world, and nearly 100% of children in the USA are infected with the virus by 2 to 3 years of age. The spectrum of clinical manifestations ranges from mild upper tract illness, infection in middle ear which progresses to acute otitis media, croup, to apnoea in premature infants, pneumonia and bronchiolitis. What isotype(s) of antibody would you suspect is in Charlie's lungs? (2 pts) RSV peptide is presented by MHC class I on the RSV specific B cells. Explain how the viral peptide gets into the MHC molecule. (6 pts) What type of T cells respond? (2 pts)
Isotypes of antibody??? IgA because it is secreted into mucus.
RSVirus gets into host cells by merging its envelop with the host cell's cytoplasmic membrane. Then the virus is inside the host cells and starts making proteins for its babies, both genetic material and structural. The host cell notices the foreign proteins and marks them for destruction with ubiquitin. The "trash" proteins are run through a proteasome where they are chewed to small bits (8-12aas) and then transported into the lumen of the ER by the TAP transporter antigen processing unit. Once inside the ER the aa's bind with MHC-1's that are being manufactured there, and the ER buds off and fuses with the cytoplasmic membrane, positioning MHC with peptide on the outside where the signal "I'm infected with RSV" will be seen by T cells. CD8 or cytotoxic T lymphocytes are the ones that respond to MHC-1 signals.
5. Your friend Tonya is heading to India to meet Ghandi’s third cousin, and visit Darjeeling where they make her favorite tea. Several vaccines are recommended. She calls you for advice. Tonya majored in conflict resolution at PSU and has never had an immunology course. Explain to Tonya 1) why having a Dengue vaccine might protect Tonya from getting Dengue fever, (4 pts) and 2) why vaccines for Dengue don't protect her against malaria (3 pts). There is an antibody response to the Dengue vaccine. Why might antibodies be protective against a virus? (3 pts)
The Dengue vaccine was not mentioned in micro so I didnt' know it existed. The micro lecture today sucked so bad that I am on the verge of not attending that class anymore. My time would be better spent studying than showing up to be scolded and told that I need to learn to be a great diagnostician by a man who can't teach his way out of a paper bag. /rant
Guessing that there is a vaccine for dengue fever, it would be a part of the virus that our immune system could recognize and generate antibodies to. If Tonya gets the vaccine and generates antibodies ahead of time, her immune response would be faster and more specific, and thus she'd be less likely to have a severe infection. That vaccine wouldn't protect against malaria because the antigens would be all different for a bacteria. If another virus had similarities to dengue, there might be cross-reactivity with the antibody recognizing the new virus as well as the one that was vaccinated for.
6. Your ex-college roommate lives in North Carolina and calls you in a panic. She just read that an “obscure virus” infected a deer hunter on her block who had been hunting in Pee Dee National Forest. A virus can get into any cell that has a receptor that the virus binds to. Yet, only APCs are capable of activating CD8 T cells that can contain the viral infection. What are APCs? (3 pts) What signals are required for CD8 T cell activation? (3 pts) How do CD8 T cells kill virally infected cells after they have been activated? (2 pts)
Your ex-college roommate just had a corneal transplant and is on immunosuppressive drugs. Her drugs only suppress T cell responses, not antibody responses. Should be worried about getting a viral infection? Why or why not? (2 pts)
7. Aunt Elsie recently had a flu vaccine. One week later, her antibody titer was measured. It was discovered that she did not make a response to the vaccine. In fact, a recent study showed that "HLA-DRB1*0701 allele was over represented among persons who fail to mount a neutralizing antibody response to influenza vaccine."
What is HLA? (2 pts) What do all of those letters and numbers following HLA mean? (4 pts) Why would HLA have to do with B cells mounting a neutralizing antibody response? (4 pts)
8. Patients with bi-polar disorder have decreased levels of IFN-gamma. What can you say about their ability to mount Th1 or Th2 responses? (3 pts) What other cytokines would you look for to determine whether they were more Th1-like or Th2-like? (4 pts)
A recent study shows that the THC in Cannabis reduces IL-12 receptor expression. Based on this information, should you recommend cannabis for your bi-polar patients and why or why not? (3 pts)
9. Georgia, a national guard who is on her way to Iraq, needs to be vaccinated for anthrax. She doesn’t want to get her vaccine right now because she has a staph infection she picked up from her volunteer work with the homeless. Can Georgia have immune responses to an infection and a vaccine at the same time? Why or why not? (3 pts)
Georgia’s boyfriend, Pete, is also on his way to Iraq. Pete has already had an anthrax infection. Does he need to worry about being vaccinated? Why or why not? (3 pts)
Georgia and Pete do some copulating in their free time in Iraq, and Georgia winds up pregnant. Will the baby need an anthrax vaccine? Explain. (4 pts)
10. Multiple Choice. 2 pts each.
_____ Which of the following organs is involved is the maturation of T cells?
_____ What do NK cells recognize?
A. MHC class I
B. The absence of MHC class I
C. MHC class II
D. The absence of MHC class II
_____ When complement attacks a bacteria
A. C3a triggers inflammation and C3b triggers the complement cascade.
B. C3a triggers the complement cascade and C3a triggers inflammation.
C. CRP causes antibody to engulf the bacteria.
D. C3b triggers the production of Reactive Oxygen Species (ROS) which kill the bacteria.
_____ If a patient has high levels of IgM, you might suspect
B. A new infection.
____ The cell that makes IL-4, IL-5, and IL-13 is called a
A. B cell.
B. Th1 cell
C. Th2 cell
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Oath: I have not cheated on this exam. _________________________________ __________________ Name Date