Immunology Chapter 6

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Immunology Chapter 6
2012-02-27 12:00:25
Ag Presentation cells

Chapter 6
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  1. Define and compare exogenous Ags and endogenous Ags.
    • 1. Exogenous Ags - Ags that originated outside of the body
    • 2. Endogenous - Ags that were generated inside the body due to abnormal metabolism or infection
  2. How are exogenous and endogenous Ags processed and presented?
    • Endogenous Ags
    • 1. Degraded in the cytosol of any cell
    • 2. Peptide fragments bind to MHC I molecules
    • 3. Presented to CD8 T cells
    • 4. Results in cell death
    • Ags in a Mf (Intravesicular Ag)
    • 1. Degraded in endocytic vessicle in Mfs
    • 2. Peptide fragments bind to MHC II molecules
    • 3. Presented to CD4 T cells
    • 4. Results in Mf activation to kill intravesicular bacteria/parasites
    • Exogenous Ags
    • 1. Degraded in endocytic vessicles in B cells
    • 2. Peptide fragments presented to MHC II molecules
    • 3. Presented to CD4 T cells
    • 4. Results in activation of B cells to secrete Abs to eliminate extracellular bacteria/toxins
  3. What is the location and function of TAP (Transporters associated with Ag processing)?
    • 1. Location - spans the ER membrane
    • 2. Function - Actively transports (ATP) peptides that bind MHC I molecules from the cytosol to the ER
  4. What is the basic function of the proteasome and how is it regulated?
    • 1. Degrades proteins into peptides
    • 2. Peptides that are presented by MHC I molecules are generated by the proteasome
    • 3. Proteosome exists in all cells as inactive constituitive proteasome
    • 4. Stimulated by interferons, the constituitive proteasome becomes the active immunoproteasome
  5. Describe in detail the pathway for peptide loading onto MHC I molecules
    • 1. Partly folded MHC I alpha chians bind to calnexin until beta2-microglobulin binds
    • 2. This complex is released from calnexin and binds to chaperons, which bind to TAP via tapasin
    • 3. Peptide fragments created by the proteosome in the cytosol are transported into the ER by TAP
    • 4. A peptide fragment binds to MHC I which completes its folding and is transported to the cell membrane
  6. How do viruses evade Ag processing and presentation pathways of the host cell
    • 1. See Fig. 6.7
    • 2. Viral evasins block Ag presentation by preventing peptide movement through TAP
    • 3. Some adenoviruses can compete with tapasin and inhibit peptide loading onto nascent MHC I
    • 4. Herpes virus ligase can target MHC I for degradation by the proteasome
  7. Describe in detail the pathway for peptide loading onto MHC II molecules.
    • 1. Invariant chain binds in the grove of MHC II
    • 2. Invariant chain is cleaved in an acidified endosome, leaving a short peptide fragment (CLIP) still bound in the MHC II groove
    • 3. Ag is taken up from extracellular space into endosome
    • 4. Acidification of endosome activates proteases to degrade Ag into peptide fragments
    • 5. HLA-DM binds to MHC II, releasing CLIP and allowing Ag peptide fragments to bind
    • 6. MHC II:Ag complex moves to cell surface
  8. Why is cross-presentation necessary to the antiviral immune response?
    • 1. The process by which extracellular proteins taken up by DCs can give rise to peptides presented by MHC I molecules
    • 2. Allows Ag from extracellular sources to be presented on MHC class I molecules and activate CD8 T cells
  9. What are the possible molecular pathway of cross-presentation?
    • 1. Translocation of ingested proteins from phagolysosome into the cytosol -> degradation by proteasome -> enter ER through TAP -> loaded onto MHC I molecule
    • 2. Transport of Ag directly from phagolysosome into a vesicular campartment -> peptides bind to MHC I molecules
  10. Define polygeny.
    Containing several separate loci encoding MHC molecules of identical functions
  11. Define polymorphism.
    • 1. MHC genes with more than one allele at a gene locus
    • 2. Allelic variation
  12. Define codominant.
    • 1. MHC product of both alleles at a locus are expressed equally in the cell
    • 2. Both gene products can present Ags to T cells
  13. Define monomorphic.
    MHC genes with only one allele
  14. Define MHC haplotype
    The particular combination of MHC alleles found on a single chromosome
  15. What is are the mechanisms that drive gene evolution in the MHC?
    • 1. Ancestral MHC gene undergoes gene duplication and divergence resulting in multiple genes
    • 2. Multiple genes undergo gene conversion between misaligned chromosomes during meiosis
    • 3. DNA sequences from one chromosome is substituted on the other
  16. What is MHC restriction?
    • 1. The fact that an Ag can only be recognized by a given T cell if it is bound to a particular self MHC molecule
    • 2. A consequence of events that occur during T cell development
  17. What is alloreactivity?
    The recognition by T cells of MHC molecules other than self
  18. How do you test for alloreactivity
    • 1. Mixed lymphocyte rxn
    • 2. lymphocytes from donor and recipient are cultured together
    • 3. If the 2 people are histoincompatible, the recipient's T cells recognize the allogeneic MHC molecules on the cells of the donor as 'foreign' and proliferate
  19. What are superAgs and how do they function?
    • 1. Bind simultaneously MHC II molecules and V-beta domains of TCRs
    • 2. Cause massive production of cytokines by CD4 T cells
    • 3. Results in toxic shock syndrome
  20. Why is it important to have extensive MHC polymorphism in a population?
    MHC polymorphism extends the range of Ag to which the immune system can respond
  21. What is the function of MIC-A and MIC-B?
    • 1. Expressed in the GI tract
    • 2. Stressed-induced activation of NK and CD8 cells
  22. What is the function of HLA-E?
    NK cell inhibition
  23. What is the function of HLA-G?
    Modulates maternal/fetal interaction
  24. What is the basic function of CD1?
    • 1. Small family of MHC class I-like proteins
    • 2. Not encoded in the MHC
    • 3. Can present glycolipid Ags to CD4 T cells