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2010-02-23 22:24:31
immunology HLA usp james donaldson zinc

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  1. What epitope system (discussed in class) exists on nucleated cells, that is, most of the cells in our body.
    HLA - Human Leukocyte Antigen - epitope system.
  2. The expression of the HLA epitope system is controlled by genes on a section of chromosome # _____ - a section known as the _______.
    • 1.) Chromosome # 6
    • 2.) Major histo-compatibility complex (MHC)
    • (Not to be confused with HLA, an epitope system. The MHC is a piece of DNA).
  3. The epitopes of the HLA system are (peptides, glycopeptides).
    Peptides (protein epitopes).
  4. The MHC can be broken into 3 parts/regions.
    Out of classes 1,2 and 3, which code for proteins of the same shape? Different shapes?
    Classes 1 and 2 code for proteins of the same shape. Class 3 codes for proteins of different shapes.
  5. What 3 genes of interest reside in the class 1 region? Class 2 region?
    • Class 1: HLA- A,B & C
    • Class 2: HLA- DP, DQ & DR

    Each of these genes codes for a different form of the peptide and associated epitopes.
  6. A class 1 molecule (from the class 1 region of the MHC), has _____ domains, what are they?
    5 domains: alpha 1, 2 & 3. A transmembrane domain. A cytoplasmic domain.
  7. A class 2 molecule (from the class 2 region of the MHC), has _____ domains, what are they?
    8 domains: beta 1 & 2, alpha 1 & 2, 2 transmembrane domains, 2 cytoplasmic domains.
  8. True or False?
    A class 1 molecule has a beta2 subunit associated with it that is not directly a part of the overall molecule.
  9. A class 1 molecule contains ______ total peptide(s), and so ______ gene(s) is/are needed to code for it. A class 2 molecule contains ______ total peptide(s), and so ______ gene(s) is/are needed to code for it.
    • Class 1: 1 total peptide and therefore one of the three HLA A,B or C genes.
    • Class 2: 2 total peptides and therefore two genes. Ex DQA or DQB
  10. What are the 4 functions of the MHC molecules of the HLA epitope system?
    • 1.) Epitopes aid in self recognition
    • 2.) Aid in cell-cell communication (helping immune response)
    • 3.) Certain HLA epitopes are associated with certain diseases
    • 4.) Man-made: organ & tissue transplantation
  11. Class II MHC molecules are only found on which type of cells?
    Antigen presenting cells (macrophages, dendritic cells, and B-cells [including langerhans]).
  12. Where does the APC place the IDP to present to a T-helper cell?
    In the peptide binding groove.
  13. True or False?
    Class I MHC molecules are on all nucleated body cells.
  14. How will a class I cell respond to its own viral infection?
    It will place a viral protein in the cleft of an MHC I molecule to attract a CTL. If a CTL finds it in time, it will kill the cell before the virus proliferates and breaks free. Cancer cells do this as well.
  15. True or False?
    Class I and II genes of the MHC has only about 12 alleles.
    • False.
    • Each gene has around 500 - 600 alleles, most of which code for epitopes.
  16. True or False?
    Even though there are approximately 2,000 epitopes in the HLA-system, any given individual only has about 12.
    • True.
    • If inbreeding is an issue, offspring could contain one or more fewer epitopes.
  17. Describe Type I diabetes.
    Autoimmune disease in which the immune system attacks its own Beta cells of pancreas, leading to little or no insulin in body.
  18. What epitope(s) is/are associated with Type I diabetes?
    DQ8 and DQ2.
  19. Describe the concept of relative risk.
    If you have a given disease, it is likely that you have the associated epitope(s). However, if you have the epitope, it is not necessarily likely that you have or will develop the disease.
  20. What epitope(s) is/are associated with Angelosing spondelitis (rare arthritic condition of lower spine)?
  21. What is the relative risk for type I diabetes? Angelosing spondelitis? Explain.
    • 1.) 14
    • 2.) 150

    If you have DQ8 and DQ2, you chances of developing type I diabetes is 14 times greater than someone without the epitopes.
  22. Type II diabetes is less often caused by an autoimmune disease, explain this disease.
    Antibodies are produced against insulin receptors on somatic cells.
  23. What is the formula for relative risk?
    RR= (P+ x C-) / (P- x C+)

    • P=patient with disease
    • C=control without disease
    • + = presence of epitope
    • - = absence of epitope

    "exceptions" = P- and C+
  24. What benefits can be offered from disease-state predictions based on the HLA epitope system?
    • 1.) Delayed onset of symptoms
    • 2.) Prevention of symptoms or disease entirely
    • 3.) Reduction of symptoms
  25. What serves as the anchor points for an IDP in the cleft of an MHC I or II molecule?
    Four amino acid side-chains at the bottom of the cleft. The IDP must be attached to these four amino acids in order for a presentation to be made.
  26. True or False?
    There are four different versions of the MHC class II molecule. An IDP must anchor to one of the four in order to be presented to a TH0 cell.
    • False.
    • There are six versions of the MHC II.
  27. What factors influence whether or not an IDP will anchor to the four amino acids within an MHC cleft?
    • 1.) Charges on atoms and functional groups
    • 2.) Amino acid side-chains of IDP and how they match and aline in a manner that favors binding
    • 3.) Weak bonds that can be made (H-bonds, hydrophobic bonds, Van Der Waals)
  28. If an IDP cannot properly anchor into any of the 6 MHC II molecules, what is the result?
    The normal immune "cascade" that takes place upon presentation cannot occur, and the individual is considered immunologically incompetent to that immunogen.
  29. Epitopes on Class II MHC molecules are located on which domain(s)? Class I?
    • 1.) Beta 2 domain
    • 2.) Alpha 1 and alpha 2 domains