The Ecology of Humans (7-10) Phagocytosis

 Phagocytosis

Essential bodily cleansing at the cellular level involves various processes, covered under the general heading of phagocytosis, which involves particulate pickup, either for nutrient acquisition, debris collection, or pathogen purging. (In applying to selfsame functioning (particle pickup) for distinct reasons, the term phagocytosis is overloaded.)

Phagocytosis is a primitive biological mechanism. Protists use phagocytosis as a means for feeding, as do amoeba. In mammals, phagocytosis involves engulfing pathogens as an immune system function.

Autophagy (aka autophagocytosis) recycles cell bits for nutritional reasons, without regard to infection; providing cells with needed nutrients not otherwise immediately available.

Traumatic cell death, from injury, is necrosis. By contrast, apoptosis is programmed cell death.

Biochemical events cause cell changes which lead to natural demise. But a dying cell has reusable parts.

Apoptotic cells emit a specific “eat me” signal to which macrophages respond, processing degraded cells into useful nutrients for other cells, and for new cell production. This process is efferocytosis. One benefit of efferocytosis is avoiding toxic spills, as terminal cells are processed before leaking into surrounding tissue.

During development and throughout life, cells are eliminated by programmed cell death and rapidly cleared by phagocytes such as macrophages and glia. Failures in apoptotic cell clearance (efferocytosis) contribute to disease. ~ English immunologist Iwan Robert Evans et al

Efferocytosis triggers specific downstream intracellular activity, including signals to reduce inflammation and promote growth. Conversely, impaired efferocytosis allows tissue damage, and is a factor in autoimmune disorders.

The reason is that phagocytes are distracted from the critical tasks of fighting infections and wound repair if tissues are junked up with debris. An ineffective efferocytosis program has phagocytes clearing crud when they should be repairing infrastructure or chasing down germs.

Another aspect of phagocytosis is pathogen disposal. There are several types of specialized phagocytic cells, including macrophages and granulocytes. Phages are leukocytes, or white blood cells, of which there are several types. Macrophages recognize microbial invaders, grab them by an antibody tail sticking out, engulf them, and then destroy them with a controlled molecular explosion: releasing a respiratory burst of reactive oxygen species (ROS).

ROS are chemically reactive oxygen-bearing molecules. Besides acting as a microbial murder weapon, ROS forms as a natural byproduct of normal oxygen metabolism. ROS is also involved in intercellular signaling.

When a plant recognizes an attacking pathogen, an immediate response is rapidly producing superoxide or hydrogen peroxide to strengthen the cell wall. This prevents the pathogen from spreading to other parts of the plant. Floral ROS response essentially forms a net around the pathogen, restricting its movement and reproduction.

Macrophages also ingest free-floating antigens that have been tagged with antibodies, including toxins. Picked up particles are shunted to a lysosome: the cellular internal recycler and garbage disposal unit. Inside the lysosome membrane, digestive enzymes work at an acidic 4.5 pH: breaking down engulfed materials, which can include amino acids, sugars, and fats. The macrophage keeps what it needs and releases the rest for use by neighboring cells.

Professional phagocytes recognize the enemy using a set of pattern recognition receptors which are activated by molecular patterns specific to the surface of infectious agents. These patterns are essentially the polysaccharides and polynucleotides which are characteristic of pathogens but not found in host cells or commensal microbes.

Polysaccharides are complex polymeric carbohydrate structures. Bacteria carry a diverse range of polysaccharides, the production of which is tightly regulated and energy intensive.

Bacterial polysaccharides have a variety of functions, ranging from maintaining cell wall integrity to helping bacteria survive in harsh environments, which includes being inside an animal. Pathogenic bacteria commonly produce a thick, mucous-like layer of polysaccharides to cloak antigenic proteins that would reveal their presence; but the polysaccharides can also be a tell.

Polynucleotides are biopolymer molecules comprising 13 or more nucleotide monomers covalently bonded into a chain, and intricately folded. All living organisms have polynucleotides, serving a vast variety of roles. One critical function is replication. The genome of every living organism comprises complementary pairs of enormously elongated polynucleotides wound around each other in the form of a double helix, then folded into an intricate origami. RNA and DNA are polynucleotides.

By and large phage receptors are lectin-like: binding multivalently, with considerable specificity, to polysaccharides exposed on the surface of an invading microbe. Lectin is a carbohydrate-binding protein.

Receptor engagement generates a signal through a NFĸB (nuclear factor-kappa B) transcription factor pathway. NFĸB is a protein complex that controls the movement or transcription of a polynucleotide. The signal alerts a phage, initiating phagocytosis.

Pathogen recognition stimulates a phagocyte to call for help by producing chemokines: proteins which summon other helpful cells to the infection site.