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FIRST HALF OF TODAY’S CLASS: THE IMMUNOGLOBULINS

Learn about IgG, IgM, IgA, IgD, and IgE, their functions, concentrations, and structures. Understand isotypes, allotypes, and idiotypes in immunoglobulins.

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FIRST HALF OF TODAY’S CLASS: THE IMMUNOGLOBULINS

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  1. FIRST HALF OF TODAY’S CLASS: THE IMMUNOGLOBULINS

  2. 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

  3. 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.

  4. 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.

  5. Some visual reinforcement…

  6. Some more visual reinforcement…

  7. 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

  8. 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.

  9. Visual reinforcement…

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

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

  12. And, there are subtypes, too

  13. 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.

  14. 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.

  15. Isotypes, allotypes, & idiotypes

  16. 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.) • Ig’s 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.)

  17. Visual reinforcement…

  18. 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.)

  19. Time to review…

  20. 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! Time to review…

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