Page 27 - Essential Haematology
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Chapter 1  Haemopoiesis  /  13


                      cells swell, the plasma membrane loses integrity.      1      Immunoglobulin superfamily     Th is  includes

                      There is usually an infl ammatory  infi ltrate  in   receptors that react with antigens (the  T - cell
                      response to spillage of cell contents. Autophagy is   receptors and the immunoglobulins) and antigen -
                      the digestion of cell organelles by lysosomes. It may     independent surface adhesion molecules.

                      be involved in cell death but in some situations also      2      Selectins     These are mainly involved in leucocyte
                      in maintaining cell survival by recycling nutrients.     and platelet adhesion to endothelium during

                                                                  inflammation and coagulation.
                                                                   3      Integrins      These are involved in cell adhesion

                          Transcription  f actors                 to extracellular matrix (e.g. to collagen in
                                                                  wound healing and in leucocyte and platelet
                       Transcription factors regulate gene expression by
                                                                  adhesion).

                      controlling the transcription of specific genes or

                      gene families. Typically, they contain at least two    The adhesion molecules are thus important in the
                      domains: a  DNA - binding domain  such as a leucine   development and maintenance of infl ammatory
                      zipper or helix - loop - helix motif which binds to a   and immune responses, and in platelet – vessel wall
                      specific DNA sequence, and an  activation domain    and leucocyte – vessel wall interactions. Expression

                      which contributes to assembly of the transcription   of adhesion molecules can be modifed by extracel-
                      complex at a gene promoter (Fig.  1.9 ). Mutation,   lular and intracellular factors and this alteration of
                      deletion or translocation of transcription factors   expression may be quantitative or functional. IL - 1,
                      underlie many cases of haematological neoplasms.     TNF, IFN -  γ , T - cell activation, adhesion to extracel-
                                                                lular proteins and viral infection may all up - regulate
                                                                expression of these molecules.
                          Adhesion  m olecules

                                                                    The pattern of expression of adhesion molecules
                       A large family of glycoprotein molecules termed   on tumour cells may determine their mode of
                      adhesion molecules mediate the attachment of   spread and tissue localization (e.g. the pattern of
                      marrow precursors, leucocytes and platelets to   metastasis of carcinoma cells or non - Hodgkin lym-

                      various components of the extracellular matrix, to   phoma cells into a follicular or diffuse pattern). Th e
                      endothelium, to other surfaces and to each other.   adhesion molecules may also determine whether or

                      The adhesion molecules on the surface of leucocytes   not cells circulate in the bloodstream or remain


                      are termed receptors and these interact with mole-  fixed in tissues. They may also partly determine
                      cules (termed ligands) on the surface of potential   whether or not tumour cells are susceptible to the

                      target cells. Three main families exist:   body ’ s immune defences.


                                  ■   Haemopoiesis (blood cell formation) arises   infants and young children haemopoietic

                           from pluripotent stem cells in the bone   tissue extends down the long bones of the
                           marrow. Stem cells give rise to progenitor   arms and legs.

                           cells which, after cell divisions and         ■    Stem cells reside in the bone marrow in   SUMMARY

                           differentiation, form red cells, granulocytes   niches formed by stromal cells and
                           (neutrophils, eosinophils and basophils),   circulate in the blood.
                           monocytes, platelets and B and T           ■    Growth factors attach to specifi c cell


                           lymphocytes.                            receptors and produce a cascade of


                              ■    Haemopoetic tissue occupies about 50%   phosphorylation events to the cell
                           of the marrow space in normal adult     nucleus. Transcription factors carry the
                           marrow. Haemopoiesis in adults is       message to those genes that are to be
                           confi ned to the central skeleton but in     ‘ switched on ’ , to stimulate cell division,
                                                                                            (Continued)
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