1. Describe the structure of IgG antibodies
    • Consist of 4 polypeptide chains (two identical heavy chains and two identical light chains)
    • Disulfide bonds link the heavy chains to eachother and the heavy chains to the light chains
  2. Describe avidity vs affinity
    • avidity: strength of simultaneous binding to 2 identical antigens
    • affinity: strength of interaction between a single antigen-binding site and its antigen
  3. What are the 5 heavy-chain classes for immunoglobulin?  Brief structure and function
    • Only vary in the constant region of Ab - variable region looks similar for all ("V shape")
    • IgM: First class produced after B cell activation
    • secreted as pentamer (huge) - not in tissues
    • lysis and agglutination
    • IgG: most common (blood and tissues)
    • Y shape
    • opsonization
    • IgA: secreted in mucosal surfaces, mothers milk, etc
    • dimer + J chain and secretory component
    • blocks entry of microorganisms
    • IgE: defense against multicellular parasites
    • bind to mast cell/basophill (allergy)
    • IgD:
    • function unknown
  4. What are the two light chain types for immunoglobulin?
    • λ (lambda) and κ (kappa)
    • B lymphocytes express only one type that remains fixed for its life
  5. Protein domain vs protein motif
    • Domain: compactly folded region of protein structure
    • Motif: sequence of AA w/ unique f(x) found within a domain
  6. What proteases can be used to cleave an antibody and into what fragments?
    • papain: 2 Fab fragments + 1 Fc fragment
    • pepsin: 1 F(ab')2 fragment + many small pieces of Fc fragment
  7. What are the two types of flexibility in an antibody molecule?  What is the benefit?
    • At the hinge
    • At the junction between the V and C domains
    • The antibody can bind to repeated antigens that are not directly adjacent
  8. What is the name for the varying regions and constant regions in the V region of an antigen, and how are they related to its secondary structure?  Is there an alternate (more appropriate) name for the varying regions?
    • There are three hypervariable regions (HV1, HV2, HV3) surrounded by framework regions (FR1, FR2, FR3, FR4)
    • The framework regions form the β sheets (structure framework)
    • The hypervariable regions form the outer edge of the β barrels (point of contact for antigens) and are termed complementarity-determining regions (CDRs) (CDR1, CDR2, CDR3)
  9. What are the two kinds of epitopes?
    • Continuous or linear: single segment of a peptide chain
    • Conformational or discontinuous: discontinuous sequentially, but nearby due protein folding
  10. Describe the structure of a TCR.  How do they differ from BCR?
    • Each T cells has ~30,000 identical TCR
    • T-cell receptors are heterodimers (α chain and β chain)
    • The αβ heterodimer is analogous to the Fab fragment of an antibody
    • Unlike BCR, TCR have only one antigen binding site and are never secreted
  11. Describe the molecular structure of MHC I and MHC II molecules
    • MHC I: 2 polypeptide chains (only α spans membrane)
    • α - forms 3 domains (α1, α2, α3)
    • α1 and α2 form the peptide binding cleft
    • β2-microglobulin - forms 1 domain, noncovalently associated with the α chain
    • MHC II: 2 polypeptide chains (both span membrane)
    • α - forms 2 domains (α1, α2)
    • β - forms 2 domains (β1, β2)
    • α1 and β1 form the peptide binding cleft
  12. What types of molecules does MHC I bind?  How does it stabilize such a variety of molecules?
    • short peptides (8-10AA)
    • stabilized at both ends of the peptide-binding cleft by invariant sites (Tyrosine residues)
    • Variations in length are accommodated by kinking the peptide backbone
    • Varying peptides can bind due to conserved "anchor residues"
  13. What is the difference between an anchor residue and a conserved polymorphic residue?
    • Anchor residue: similar amino acid residues in specific positions on a peptide
    • Conserved polymorphic residue: residues on an MHC molecule that interact with anchor residues
    • conserved in a given MHC molecule, but polymorphic in a population
  14. What types of molecules does MHC II bind?  How does it differ from MHC I binding? How does it stabilize such a variety of molecules?
    • longer peptides (13+ AA)
    • No conserved Tyr residues (the ends of a peptide are not bound)
    • Polymorphic residues' interactions with anchor residues hold the peptide in place
  15. What are the two T cell co-receptors?  What types of cells have them? Which MHC molecules recognize them?
    • CD4: helper T cells, MHC II
    • CD8: cytotoxic T cells, MHC I
  16. Describe the structural difference between CD4 and CD8 co-receptors.  How do they function?
    • CD4: single chain of 4 Ig-like domains (D1-D4)
    • CD8: dimer of 2 chains (α and β) that each link to the membrane
    • Both bind Lck (a cytoplasmic tyrosine kinase) on MHC and bring it close to the TCR, increasing sensitivity by ~100x
  17. On what cells can MHC I and II molecules be found? Why?
    • MHC I: expressed on all nucleated cells
    • used to express viral infection
    • MHC II: expressed on B lymphocytes, dendritic cells, and macrophages (APCs)
    • activate B cells/macrophages
    • induce naive helper T cell maturation
  18. What regulates MHC I and II expression?  Specifically what regulates each and how?
    • Interferons released during immune response
    • IFN-α and IFN-β increase MHC I expression in all cell types
    • IFN-γ increases MHC I expression in virus-infected cells and MHC II expression in macrophages and other cells which may not normally express MHC II
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