Phagocytic immunity

Phagocytic immunity The phagocytic arm of the immune system can be divided into two major groups: the circulating and fixed components. Circulating cells with phagocytic capacity include all of the granulocytes (including eosinophils) and the monocytes. The fixed tissue phagocytes include cells of the monocyte/macrophage lineage, specifically Kupffer cells of the liver, splenic macrophages, pulmonary alveolar macrophages, lymph node macrophages, and the microglial cells of the brain. Together, the fixed-tissue phagocytes are referred to as the reticuloendothelial system. The ability of the granulocytes, monocytes, and macrophages to destroy foreign antigen by phagocytosis is crucial for host defense. Failure of either of these systems invariably results in an increased susceptibility to infection.

The following steps are necessary for adequate phagocytosis and destruction of foreign antigen:

• random movement ;
  
• neutrophil adherence to vascular endothelium;
  
• transmembrane migration (diapedesis) ;
  
• chemotaxis ;
  
• opsonization and fixation of the bacteria or foreign material;
  
• ingestion of the antigen;
  
• metabolic activation of the phagocytes to destroy the foreign material;
  
• destruction of the organism. Specific features of this system are as follows.
  

A. Phagocytic cells migrate either in a random manner or in response to biochemical signals. This directed movement is called chemotaxis. Known chemoattractants include the activated complement components C3a, C4a, C5a, bacterial products, various leukotrienes, and other arachidonic acid metabolites.

B. Opsonization is the process by which antibody coats a bacterial cell wall or foreign material and increases its susceptibility to phagocytosis.

C. Phagocytosis is the process of engulfing foreign material into the phagocytic cell. After an intracellular phagocytic vacuole, or phagosome, is formed around the foreign material, lysosomal enzymes are released into this vacuole, resulting in the degradation of the foreign material. Neutrophil-generated, oxygen free radicals also play an important role in the destruction of phagocytosed microbes. Stimulated neutrophils can use the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase directly to generate superoxide anion radicals, which are rapidly converted to hydrogen peroxide and hydroxyl radicals. The latter two metabolic products provide the majority of the microbicidal activity in the phagosome. When halides and myeloperoxidase are present in the phagosome, hypochlorous acid and free halides are generated. During this process an increased burst of metabolic activity, with increased oxygen consumption, can be measured and used to assess neutrophil- killing capacity.