Page 151 - Textbook of Pathology, 6th Edition

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CHAPTER 6

Figure 6.6 Stages in phagocytosis of a foreign particle. A, Opsonisation of the particle. B, Pseudopod engulfing the opsonised particle.
C, Incorporation within the cell (phagocytic vacuole) and degranulation. D, Phagolysosome formation after fusion of lysosome of the cell.

1. Recognition and attachment Disposal of microorganisms can proceed by following Inflammation and Healing
2. Engulfment mechanisms:
3. Killing and degradation A. Intracellular mechanisms:
i) Oxidative bactericidal mechanism by oxygen free radicals
1. RECOGNITION AND ATTACHMENT
Phagocytosis is initiated by the expression of surface a) MPO-dependent
receptors on macrophages which recognise microorganisms: b) MPO-independent
mannose receptor and scavenger receptor. The process of ii) Oxidative bactericidal mechanism by lysosomal granules
phagocytosis is further enhanced when the microorganisms iii) Non-oxidative bactericidal mechanism
are coated with specific proteins, opsonins, from the serum B. Extracellular mechanisms:
or they get opsonised. Opsonins establish a bond between These mechanisms are discussed below.
bacteria and the cell membrane of phagocytic cell. The main A. INTRACELLULAR MECHANISMS. There are
opsonins present in the serum and their corresponding intracellular metabolic pathways which more commonly kill
receptors on the surface of phagocytic cells (PMNs or microbes by oxidative mechanism and less often non-
macrophages) are as under:
oxidative pathways.
i) IgG opsonin is the Fc fragment of immunoglobulin G; it is i) Oxidative bactericidal mechanism by oxygen free
the naturally occurring antibody in the serum that coats the radicals. An important mechanism of microbicidal killing is
bacteria while the PMNs possess receptors for the same. by oxidative damage by the production of reactive oxygen
ii) C3b opsonin is the fragment generated by activation of metabolites (O’ H O , OH’, HOCl, HOI, HOBr).
2
2
2
complement pathway. It is strongly chemotactic for attracting A phase of increased oxygen consumption (‘respiratory
PMNs to bacteria. burst’) by activated phagocytic leucocytes requires the
iii) Lectins are carbohydrate-binding proteins in the plasma essential presence of NADPH oxidase.
which bind to bacterial cell wall. NADPH-oxidase present in the cell membrane of
phagosome reduces oxygen to superoxide ion (O’ ):
2. ENGULFMENT 2
The opsonised particle bound to the surface of phagocyte is 2O 2O’
ready to be engulfed. This is accomplished by formation of 2 2
cytoplasmic pseudopods around the particle due to NADPH (Superoxide
activation of actin filaments beneath cell wall, enveloping it oxidase anion)
in a phagocytic vacuole. Eventually, the plasma membrane
enclosing the particle breaks from the cell surface so that NADPH NADP + H +
membrane lined phagocytic vacuole or phagosome lies
internalised and free in the cell cytoplasm. The phagosome Superoxide is subsequently converted into H O which
2
2
fuses with one or more lysosomes of the cell and form bigger has bactericidal properties:
vacuole called phagolysosome. 2O’ + 2H + H O 2
2
2
(Hydrogen peroxide)
3. KILLING AND DEGRADATION
Next comes the stage of killing and degradation of micro- This type of bactericidal activity is carried out either via
organism to dispose it off justifying the function of enzyme myeloperoxidase (MPO) present in the azurophilic
phagocytes as scavanger cells. The microorganisms after granules of neutrophils and monocytes, or independent of
being killed by antibacterial substances are degraded by enzyme MPO, as under:
hydrolytic enzymes. However, this mechanism fails to kill a) MPO-dependent killing. In this mechanism, the enzyme
and degrade some bacteria like tubercle bacilli. MPO acts on H O in the presence of halides (chloride, iodide
2
2