Phagocytic Cells Engulf And Kill Microorganisms
Macrophages and neutrophils are dedicated “professional” phagocytes
The engulfment and digestion of microorganisms are assigned to two major cell types recognized by Elie Metchnikoff at the turn of the last century as microphages (now known as neutrophils) and macrophages.
These cells derive from bone marrow promonocytes that, after differentiation to blood monocytes, finally settle in the tissues as mature macrophages where they constitute the mononuclear phagocyte system (Figure 1.24). They are present throughout the connective tissue and around the basement membrane of small blood vessels and are particularly concentrated in the lung (alveolar macrophages), liver (Kupffer cells), and lining of spleen sinusoids and lymph node medullary sinuses, where they are strategically placed to filter off foreign material. Other examples are mesangial cells in the kidney glomerulus, brain microglia, and osteoclasts in bone. Unlike neutrophils, macrophages are longlived cells with significant rough‐surfaced endoplasmic reticulum and mitochondria and, whereas neutrophils provide the major defense against pyogenic (pus‐forming) bacteria, as a rough generalization it may be said that macrophages are at their best in combating those bacteria, viruses, and protozoa that are capable of living within the cells of the host.
The polymorphonuclear neutrophil
This cell, the smaller of the two, shares a common hematopoietic stem cell precursor with the other formed elements of the blood and is the dominant white cell in the bloodstream. It is a nondividing short‐lived cell with a multilobed nucleus and an array of granules (Figure 1.9 and Figure 1.25), which are virtually unstained by histologic dyes such as hematoxylin and eosin, unlike those structures in the closely related eosinophil and basophil (Figure 1.9). Neutrophil granules are of two main types: (i) the primary azurophil granule that develops early, has the typical lysosomal morphology and contains myeloper- oxidase, together with most of the nonoxidative antimicrobial effectors including defensins, bactericidal permeability increasing (BPI) protein, and cathepsin G (Figure 1.25); and (ii) the peroxidase‐negative secondary specific granules containing lactoferrin, much of the lysozyme, alkaline phosphatase and membrane‐bound cytochrome b558 (Figure 1.25). The abundant glycogen stores can be utilized by glycolysis, enabling the cells to function under anerobic conditions.
Microbes are engulfed by activated phagocytic cells
After adherence of the microbe to the surface of the neutrophil or macrophage through recognition of a PAMP (Figure 1.26b), the resulting signal (Figure 1.26c) initiates the ingestion phase by activating an actin–myosin contractile system that extends pseudopods around the particle (Figure 1.26d and Figure 1.27); as adjacent receptors sequentially attach to the surface of the microbe, the plasma membrane is pulled around the particle just like a “zipper” until it is completely enclosed in a vacuole (phagosome; Figure 1.26f and Figure 1.27). Events are now moving smartly and, within 1 minute, the cytoplasmic granules fuse with the phagosome and discharge their contents around the imprisoned microorganism (Figure 1.26 g and Figure 1.28) subjecting them to a formidable battery of microbicidal mechanisms.