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130  /  Chapter 9  White cells: Lymphocytes


                    When HLA molecules are absent on the target cell  of normal serum immunoglobulin and is further
                    this inhibitory signal is lost and the NK cell can  subdivided into four  subclasses : IgG  1  , IgG  2  , IgG  3
                    then kill its target. In addition, NK cells display  and IgG  4  . IgA is subdivided into two types.

                    antibody - dependent  cell - mediated  cytotoxicity     IgM is usually produced first in response to
                    (ADCC). In this, antibody binds to antigen on the  antigen, IgG subsequently and for a more

                    surface of the target cell and then NK cells bind to  prolonged period. The same cell can switch from
                    the Fc portion of the bound antibody and kill the  IgM to IgG, or to IgA or IgE synthesis. IgA is the
                    target cell.                              main immunoglobulin in secretions, particularly
                                                              of the gastrointestinal tract. IgD and IgE (involved
                                                              in delayed hypersensitivity reactions) are minor
                        Lymphocyte  c irculation
                                                              fractions. Some important properties of the three
                     Lymphocytes in the peripheral blood migrate  main immunoglobulin subclasses are summarized
                    through  post - capillary venules  into the substance  in Table  9.2 .
                    of the lymph nodes or into the spleen or bone    The immunoglobulins are all made up of the

                    marrow. T cells home to the perifollicular zones of  same basic structure (Fig.  9.3 ) consisting of two
                    the cortical areas of lymph nodes (paracortical areas)  heavy chains which are called gamma ( γ ) in IgG,
                    (Fig.  9.2 ) and to the periarteriolar sheaths sur-  alpha ( α ) in IgA, mu ( μ ) in IgM, delta ( δ ) in IgD
                    rounding the central arterioles of the spleen. B cells  and epsilon ( ε ) in IgE, and two light chains  –  kappa
                    selectively accumulate in follicles of the lymph  ( κ ) or lambda ( λ )  –  which are common to all fi ve

                    nodes and spleen. Lymphocytes return to the  immunoglobulins. The heavy and light chains each
                    peripheral blood via the efferent lymphatic stream  have highly variable regions which give the immu-


                    and the thoracic duct. CD4 helper cells predomi-  noglobulin specificity, and constant regions in
                    nate in normal peripheral blood and germinal  which there is virtual complete correspondence in
                    centres, but in the marrow and gut the major T - cell  amino acid sequence in all antibodies of a given
                    subpopulation is CD8 positive.            isotype (e.g. IgA, IgG) or isotype subclass (e.g. IgG  1  ,
                                                              IgG  2  ). IgG antibody can be broken into a constant
                                                              Fc fragment and two highly variable Fab fragments.
                        Immunoglobulins
                                                              IgM molecules are much larger because they consist

                     These are a group of proteins produced by plasma  of fi ve subunits.
                    cells and B lymphocytes that bind to antigen. Th ey    The main role of immunoglobulins is defence of

                    are divided into five subclasses or  isotypes : immu-  the body against foreign organisms. However, they

                    noglobulin G (IgG), IgA, IgM, IgD and IgE. IgG,  also have a vital role in the pathogenesis of a number
                    the most common, contributes approximately 80%  of haematological disorders. Secretion of a specifi c



                         Table 9.2   Some properties of the three main classes of immunoglobulin (Ig).

                                              IgG             IgA                     IgM
                         Molecular weight     140   000     140   000               900   000

                         Normal serum level (g/L)     6.0 – 16.0     1.5 – 4.5      0.5 – 1.5
                         Present in         Serum and         Serum and other body fl uids       Serum only
                                          extracellular fl uid    (e.g. of bronchi and gut)
                         Complement fi xation     Usual      Yes (alternative pathway)     Usual and very effi cient
                         Placental transfer     Yes         No                      No

                         Heavy chain          ( γ  1 – 4  )       α  ( α  1    or  α  2   )       μ
   139   140   141   142   143   144   145   146   147   148   149