FIRST HALF OF TODAY

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FIRST HALF OF TODAYS CLASS THE IMMUNOGLOBULINS
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A quick overview of the five immnoglobulin
classes

• IgG (( globulin) the prototypic immunoglobulin.
• All three general functions (Ag binding,
  complement activation, stimulation of
  phagocytosis) occur.
• IgM (macroglobulin) often the first
• IgA the secretory immunoglobulin
• IgD regulatory?
• IgE functions with parasites and allergens

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IgG (( globulin)

• IgG is the principal immunoglobulin of the
  secondary response.
• IgG is the principal immunoglobulin of the adult
  (but not the neonate.)
• IgG constitutes 80 of the circulating
  immunoglobulin in the adult.
• The concentration of IgG in serum is high 8-16
  mg ml-1.
• The architecture of IgG is simple
• two ( chains and two 8 chains or
• two ( chains and two 6 chains.

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IgM (macroglobulin)

• a pentamer (in secreted form) attached by
  disulfide bonds between the C4 and C3 domains of
  adjacent heavy chains
• in addition, there is a single J-protein.
• IgM is the first immunoglobulin to be synthesized
  in a primary response.
• The concentration of IgM in serum is 1.5 mg
  ml-1.
• IgM is the first immunoglobulin to accumulate in
  the serum of neonates.
• IgM has a high valency which contributes to
  agglutination. Also, multimeric nature
  contributes to effective complement activation.
• mIgM is a monomer.

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Some visual reinforcement
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Some more visual reinforcement
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co-los-trum \kc-läs-tram \ n \ L. beestings
(1577) milk secreted for a few days after
parturition and characterized by high protein and
antibody content
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IgA (the secreted antibody)

• Most often a dimer sometimes a tetramer (or a
  trimer).
• Multimers united by J-protein.
• Secretion requires addition of secretory
  component produced in mucosal epithelial cells
  (in digestive, respiratory, genital, breast
  tissues and salivary and lacrimal glands).
• Plasma cells secrete the Ab
• deliver IgA to epithelial cells having
  poly-Ig-receptor on their surface.
• The poly-Ig-receptor is cleaved and the
  component that stays associated with IgA is the
  secretory component.
• MW 70,000 daltons composed of 5
  immunoglobulin-like domains
• binds to constant regions of heavy chains.
• Movement of the receptor from one surface to
  another is transcytosis.

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Visual reinforcement
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IgD and IgE

• IgE is extremely rare.
• 0.0003 mg ml-1 serum
• IgE functions against parasites.
• In the absence of para-
• sites, IgE responds to allergens.

• IgD is very rare.
• 0.03 mg ml-1serum
• What does this imply?

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IgE

• IgE is extremely rare.
• IgE functions against parasites.
• In the absence of para-
• sites, IgE responds to allergens.

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And, there are subtypes, too
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Hinges versus domains

• Hinges contribute to flexibility. They contain
  cysteine and proline. Cysteine provides
  interchain linkage. Proline cannot be
  incorporated into secondary structure.
• Immunoglobulins without hinge regions have an
  extra domain.

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Isotypes, allotypes, idiotypes

• ISOTYPE one of the five ((, ", , , ,) major
  kinds of heavy chains in immunoglobulins. Note
  that the differences among the isotypes are in
  the constant region.
• Indeed, different isotypes can share common
  variable regions! (Think about that.)
• ALLOTYPE the allelic variation seen at loci
  specifying the light and heavy chains of
  immunoglobulins.
• IDIOTYPE The set of antigenic determinants
  (idiotopes) characterizing each unique antibody
  (or T-cell receptor). Idiotopes are single
  antigenic determinant(s) in the variable domains
  of an antibody (or T-cell receptor). Idiotopes
  are generated by the unique amino acid sequence
  specific for each antigen.

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Isotypes, allotypes, idiotypes

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IMPORTANT

• One B-cell makes one type of antibody.
• (More exactly, one B-cell makes one idiotype.)
• (This equation is the basis of monoclonal
  antibodies but we are going to ignore monoclonals
  for the time being.)
• Igs first appear on the surface of B-cells
  there they are selected.
• The B-cells mature to plasma cells and secrete
  antibodies with the same specificity (i. e., same
  idiotypic identity same antigen specificity.)

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Visual reinforcement
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Visual reinforcement

• The carboxy terminus of the mIg, penetrates into
  the cytoplasm by only a few amino acids. But mIg
  is always associated with pairs of the dimer Ig-"
  / Ig-.
• These associated dimers have longer carboxy
  tails, 61 amino acids and 48 amino acids
  respectively. The tails contain tyrosine
  residues which can be phosphorylated by kinases
  the phosphorylated or un-phosphorylated states
  constitute a molecular switch conforming to an on
  / off switch.
• (Immunological phenomena affected by kinases
  tend to use tyrosine as the receptor of
  phosphates while other cellular phenomena tend to
  use serine or threonine.)

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Time to review
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Time to review

• Isotype, allotype, idiotype
• implies that epitopes (at least experimentally)
  are proteins
• proteins are specified by genes
• how do genes specify the numerous, diverse,
  highly specific immunoglobulins? (BIG
  question!)

• Time to review
• take a 5 break!