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                                                                                                            mebooksfree.com
 mebooksfree.com  mebooksfree.com           mebooksfree.com              penicillin binds to one of our proteins to cross-link IgE. An   497  mebooksfree.com
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                                                                                                CHAPTER 57  Immunity
                        bind because they are not polypeptides and only polypep-
                        tides  can  be  presented  by  MHC  proteins.  Furthermore,
                                                                         excellent example of this is penicilloyl polylysine, which is
                        haptens are univalent and therefore cannot activate B cells
                                                                         used in skin tests to determine whether a patient is allergic
                                                                         to penicillin. Each lysine in the polylysine has a penicillin
                        by themselves. (Compare with the T-independent response
                                                                         molecule attached to it. These univalent penicillin mole-
                        of multivalent antigens discussed earlier in this chapter and
                        in Chapter 58.)
                          Although haptens cannot stimulate a primary or sec-
                                                                         cent IgEs on the surface of mast cells. The consequent
                                                                         release of mediators causes a “wheal and flare” reaction in
                        ondary response by themselves, they can do so when cova-
                        lently bound to a “carrier” protein (Figure 57–5). In this   cules form a “multivalent” array and can cross-link adja-
                                                                         the skin of the penicillin-allergic patient.
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                                                                           Another medically important concept that is related to
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                        process, the hapten interacts with an IgM receptor on the B
 mebooksfree.com  mebooksfree.com           mebooksfree.com              cines and the vaccine against Haemophilus influenzae. In          mebooksfree.com
                        cell and the hapten–carrier protein complex is internalized.
                                                                         the hapten–carrier protein model is that of conjugate vac-
                                                                         cines such as the pneumococcal and meningococcal vac-
                        A peptide of the carrier protein is presented in association
                        with class II MHC protein to the helper T cells. The acti-
                        vated helper T cell then produces interleukins, which
                                                                         these conjugate vaccines, the  capsular  polysaccharide is
                        stimulate the B cells to produce antibody to the hapten (see
                                                                         conjugated to a carrier protein. The capsular polysaccha-
                                                                         ride is not a hapten because it can induce IgM via the
                        Chapter 58, page 512, for additional information).
                                                                         T-independent response. However, adding a carrier protein
                          Two additional ideas are needed to understand how
                        haptens interact with our immune system. The first is that
                                                                         causes helper T cells to be involved, and large amounts of
                        many haptens, such as drugs (e.g., penicillin) and poison
                                                                           The interaction of antigen and antibody is highly spe-
                        oak oil, bind to our normal proteins, to which we are tol-
                        erant. The hapten–protein combination now becomes
                                                                         cific, and this characteristic is frequently used in the diag-
                        immunogenic (i.e., the hapten modifies the protein suffi-  IgG are produced via the T-dependent response.
                                                                         nostic laboratory to identify microorganisms. Antigen and
                                                                         antibody bind by weak forces such as hydrogen bonds and
                        ciently such that when the hapten–peptide combination is
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 mebooksfree.com  mebooksfree.com           mebooksfree.com              fit of the antigen with its antibody-combining site (i.e., its    mebooksfree.com
                                                                         van der Waals’ forces rather than by covalent bonds. The
                        presented by the MHC protein, it is recognized as
                        foreign).
                                                                         strength of the binding (the affinity) is proportionate to the
                          The second idea is that although most haptens are uni-
                        valent, type I hypersensitivity reactions such as anaphylaxis
                                                                         ability to form more of these bonds). The affinity of anti-
                                                                         bodies increases with successive exposures to the specific
                        (see Chapter 65) require cross-linking of adjacent IgEs to
                        trigger the release of the mediators. By itself, a univalent
                                                                         antigen (see Chapter 60). Another term, avidity, is also used
                        hapten cannot cross-link, but when many hapten molecules
                                                                         to express certain aspects of binding. It need not concern us
                        are bound to the carrier protein, they are arranged in such
                                                                         here.
                                                                           The features of molecules that determine immunoge-
                        a way that cross-linking can occur. This is how a univalent
                                                                         nicity are as follows.
                        hapten, such as penicillin, causes anaphylaxis. Sufficient
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                              Hapten part of  mebooksfree.com
 mebooksfree.com  mebooksfree.com   B   Hapten carrier protein  Helper  MHC protein  IL-4, IL-5  cell  Plasma  mebooksfree.com             mebooksfree.com
                                        Carrier protein
                                                       T cell
                                                            TCR
                                              Epitope of
                                                              Class II
                                        IgM
                                                         B
                                                                                B
                                    cell
                                                        cell
                                                                                               cell
                                                                                                          specific
                                                                                                         for hapten
                                                                             interleukins that stimulate the
                              hapten-carrier        B cell presents          Activated helper T cell produces   Antibodies
                                                    epitope of carrier
                              conjugate interacts
                                                                             B cell to become a plasma cell
                                                    protein to helper
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                              with hapten–specific
                                                                             that produces antibodies against
                                                    T cell that carries
                              IgM on the surface
                                                                             the hapten
                                                    a TCR specific
                              of a B cell
                                                    for that epitope
                    FIGURE 57–5
                                   Hapten–carrier conjugate induces antibody against the hapten. A hapten covalently bound to a carrier protein can induce
                    antibody to a hapten by the mechanism depicted in the figure. A hapten alone cannot induce antibody, because the helper T cells are not
                    activated by the hapten. Although the hapten alone (without the carrier protein) can bind to the IgM receptor on the B-cell surface, the
                    interleukins essential for the B cell to become a plasma cell are not made. TCR, T-cell receptor.
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