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Chapter 8  White cells: Granulocytes and monocytes  /  115


                      (H  2  O  2  ) and other activated oxygen (O  2  ) species, are  oxide (NO) generated through NO synthase from
                      generated from O  2   and reduced nicotinamide  L - arginine is another mechanism by which phago-
                      adenine dinucleotide phosphate (NADPH). In  cytes kill microbes.
                      neutrophils, H  2  O  2   reacts with myeloperoxidase
                      and intracellular halide to kill bacteria; activated


                      oxygen may also be involved. The  non - oxidative   Defects of  p hagocytic  c ell  f unction
                      microbicidal mechanisms involve microbicidal pro-
                                                                    Chemotaxis

                      teins. These may act alone (e.g. cathepsin G) or in
                      conjunction with H  2  O  2   (e.g. lysozyme, elastase).   These defects occur in rare congenital abnormalities


                      They may also act with a fall in pH within phago-  (e.g.  ‘ lazy leucocyte ’  syndrome) and in more
                      cytic vacuoles into which lysosomal enzymes are  common acquired abnormalities either of the envi-
                      released. An additional iron binding protein, lacto-  ronment (e.g. corticosteroid therapy) or of the leu-
                      ferrin, is present in neutrophil granules and is bac-  cocytes themselves (e.g. in acute or chronic myeloid
                      teriostatic by depriving bacteria of iron and  leukaemia, myelodysplasia and the myeloprolifera-
                      generating free radicals (Fig.  8.7 ). Finally, nitric  tive syndromes).


                                                              Bacterium
                                                Phagocytosis


                                                                           Phagosome

                                                                           Primary granule
                                                                           (contains acid
                                                                           phosphatase,
                                                                           myeloperoxidase,
                                                                           esterase)


                                       H O , activated O  species          Secondary (specific)
                                        2 2
                                                  2
                                                                           granule (contains
                                                                           lysozyme,
                                                                           elastase,
                                                                           collagenase,
                                                                           lactoferrin)
                                              NEUTROPHIL
                                                                           Residual body




                                                 Exocytosis


                                Figure 8.7   Phagocytosis and bacterial destruction. On entering the neutrophil, the bacterium is surrounded by


                      an invaginated surface membrane and fuses with a primary lysosome to form a phagosome. Enzymes from the
                      lysosome attack the bacterium. Secondary granules also fuse with the phagosomes, and new enzymes from
                      these granules including lactoferrin attack the organism. Various types of activated oxygen, generated by
                      glucose metabolism, also help to kill bacteria. Undigested residual bacterial products are excreted by
                      exocytosis.
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