Card Set Information

2011-05-15 12:39:07
Immunology MS1

Immunology Lecture 06 Syllabus
Show Answers:

  1. How a B cell switch from expressing BCR to Ig?
    RNA splicing out transmembrane region
  2. Electrophoretic mobility of serum proteins can be a tool for diagnosing ___
    • Myeloma serum vs normal serum
    • homogeneous population of IgG molecules (narrow band) indicated myeloma
  3. Bence-Jones protein
  4. light chain dimers in the urine of some patients with myeloma
    escapes filtration b/c light molecular weight
  5. Antigens recognized by BCR
    • proteins
    • peptides
    • lipids
    • carbohydrates
    • nucleic acids
    • small molecules (metallic)
  6. What is at the N terminus and C terminus of an IgG?
    • N terminus= variable region
    • C terminus= constant region
  7. Where does papain and pepsin cleave in IgG?
    • Papain cleaves to the N terminal of disulfide bonds, leaving 2 identical Fab and 1 Fc fragments
    • Pepsin cleaves to the C terminal of disulfide bonds in the hinge, generating 1 F(ab')2 fragment and heavy chain that gets degraded to small peptides
  8. Function of Fab and F(ab')2 region
    antigen binding
  9. function of Fc region
    • complement fixation
    • Antibody Dependent Cell-mediated Cytotoxicity (ADCC)
  10. ADCC
    • Antibody Dependent Cell-mediated Cytotoxicity
    • NK or macrophages targeted to IgG coated cells result in lysis of target
    • mediated by CD16 receptor binding the Fc region of IgG
  11. What experiment established the existence of 2 H and 2 L chains in Ig?
    reducing agent studies
  12. IgG is (divalent/monovalent)?
  13. Where are the variable and constant domains on an Ig?
    can be found in both the H and the L chains
  14. Which domains are responsible for complement and mediating ADCC on an Ig?
    CH2 and CH3 domains on the C terminus Heavy Chain
  15. Which chain is glycosylated/nonglycosylated: H-chain, L-chain?
    • H chain is glycosylated (on CH2 domain)
    • L chain is nonglycosylated
  16. What aa residues make up the hinge?
    Proline, cysteine
  17. Characteristics of the IgG domain
    loops of ~110 aa which show homology and have an intra-chain disulfide bond
  18. 4 regions of interaction betweeh H-L and H-H
    • VH-VL
    • CH1-CL @ hinge
    • CH2-CH2 of HC
    • CH3-CH3 of HC
  19. CDR
    • complementarity determining regions
    • aka hypervariable portions of the variable regions in HC Ig
  20. 2 parts of the V-region
    • framework region- less variable
    • hypervariable region/ CDR- most variable region
  21. 5 Ig isotypes (secreted structure, serum structure)
    • IgM in serum= (μ2L2)5J
    • IgG in secretion= γ2L2
    • IgA in secretions (α2L2)2JS
    • IgD
    • IgE
  22. Which 2 Ig don't have a hinge and have an extra C-terminal HC domain?
    IgM and IgE
  23. Distribution of Ig in the body
    • Blood: IgG (major), IgM
    • Tissue fluids: IgG (major), IgM and IgA monomer (trace)
    • Secretions: IgA dimers (major) some IgG
    • Fetus: passive IgG1, 3, and 4 from mom
    • Beneath epithelium: IgE on mast cells
    • Brain: none b/c of BBB
    • Respiratory mucosa: IgD
  24. Half-life of IgG
    23d except IgG3 which is 7d
  25. Which class of IgG is responsible for complement inding? placental passage, and monocyte binding?
    • complement binding: IgG3>>IgG1, IgG2 >>IgG4
    • placental passage: all except IgG2
    • monocyte binding: IgG1, IgG3 > IgG2 > IgG4
  26. During what phase of an immune response are IgGs secreted?
    late primary or early secondary response
  27. IgG characteristics
    • Protects fetus (IgG1, 3, 4)
    • activates complement
    • acts as an opsinizing antibody
    • mediate ADCC
    • neutralize toxins and viruses
  28. IgM characteristics
    • B cell surface: μ2λ2 or μ2κ2, no hinge
    • secreted: largest molecular wt Ig with 5 functional binding sites
    • first Ig to appear during ontogeny and during immune response
    • most effective complement activator and agglutinating antibody
    • anti-AB blood type
  29. IgD characteristics
    • B cell surface
    • sensitive to proteolysis
    • triggers IL1, TNF release in mast cells and basophils in respiratory mucosa
  30. IgE characteristics
    • reaginic antibody (related to allergy)
    • lowest serum concentration and shortest 1/2 life
    • extra H domain which bins to mast cells and basophils
    • also binds to eosinophils (protect against parasites)
  31. IgA characteristics
    • monomer in serum/cell surface; dimer in secretion
    • short half life
    • major Ig in the body and in external secretions
    • protects all mucosal surfaces
  32. Structure of secretory IgA
    • 2 tail-to-tail molecules linked by J chain at the C terminus
    • mucophillic secretory component
  33. function of secretory component of IgA
    • protect IgA from proteolysis
    • facilitate attachment to epithelia so antigens can be trapped in mucus and lysozyme can degrade the IgA-Ag complex
  34. disease related to IgA deficiency
    • congenital immunodeficiency
    • causes local infections (not systemic)
  35. Synthesis of secretory IgA
    • J chain is added to the IgA dimer in the plasma cell in lamina propria or Peyer's patch and secreted
    • GI epithelial cells express poly-Ig receptors that bind to Fc portion of IgA dimer
    • pinocytosis and exocytosis transports the IgA dimer to lumen surface
    • a piece of the poly-Ig receptor is destroyed so IgA is secreted
  36. Defense of mucosal surfaces
    • 1' encounter with pathogen will cause an infection
    • 2' response:
    • IgA secreted into lumen binds pathogen to hinder its entrance
    • IgE bound to mast cells defend against pathogens that enter mucosa
  37. How is IgG levels regulated?
    • FcRn present in endothelium and hematopoietic cells
    • IgG enters cells via pinocytosis, binds to FcRn in acidic pH=6 allows recycling to ECM.
    • excess unbound Ab is degraded by lysosomes
  38. How is IgM levels regulated?
    large amounts are synthesized during 1' response but rapidly cleared and degraded
  39. How is IgA level regulated?
    • Secretory IgA remains in gut for a long time
    • Secretory component (SC) protects against proteolysis
  40. How is IgE level regulated?
    • IgE binds to FcRs on mast cells and remain there for a long time
    • serum concentration is low
  41. How is IgD level regulated?
    • Binds to receptors of mast cells and basophils
    • serum concentration is very low
  42. 3 determinants of Ig
    • Isotypic: 5 different constant regions of HC determines class, LC also has 2 isotypes
    • Allotypic: aa differences in constant region of HC or LC; intraspecies differences
    • Idiotypic (Ids): present in the variable regions of HC or LC; anti-Id antibody serves as clonal marker for an Ig or the B cell that makes it
  43. Genetic mutations and diseases of Ig
    • Hyper IgM (CD40, CD40L, AID): recurrent infections b/c failure to class switch
    • Hyper IgE (STAT3, Tyk2): allergic type syndromes
    • Hyper-IgD (Mevalonate kinase, pyrin, TNFR): periodic fevers
    • Hypogammaglobulinemia (transient in infancy or btk mut): recurrent infections
  44. 3 major type sof TCR and what they recognize
    • αβ TCR: recognizes peptide/HLA
    • γδ TCR: recognizes peptide/HLA
    • NK TCR: recognizes glycolipid/CD1d
  45. how are the 2 chains of a TCR joined?
    a single disulfide bond near te plasma membrane
  46. distribution of TCR types throughout body
    • αβ TCR: throughout the body
    • γδ TCR: skin, mucosa, gut
  47. TCR complex components
    • responsible for signaling once TCR has bound to antigen
    • CD3γε (part of immunoglobulin supergene family)
    • CD3δε (part of immunoglobulin supergene family)
    • ζζ
  48. constant portion of TCR
    • CD3
    • contains cytosol region that mediates signal transduction
  49. SCID symptoms and genetic mutaiton
    • recurrent bacterial and viral infections
    • ZAP70, CD3 (δ, ε, ζ), Rag
  50. DiGeorge syndrome genetic mutations
    • recurrent bacterial and viral infections
    • 22q11, 10p