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.
The macrophage
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.
