BiTherapca Health

Chronic infections start as acute infections. Some acute infections resolve while others take a chronic course. The infective agent as well as the immune system plays an active role in  the outcome of the disease. Normally, most infections are resolved, aided by treatment or not, by phagocytosis when the microbes are still in their discrete, planktonic forms. To start with, mast cells degranulate, in the presence of an infective agent, or a solid particle that provides shear strain or stress-- and may eventually lead to allergy if antigenic. Allergens cause the cross-linking of IgE on mast cells and the mechanical shear therefrom causes degranulation. Mast cell degranulation releases histamine, heparin, prostaglandin D2, leukotriene C4 as well as chymase and tryptase--serine proteases, hydrogen peroxide, oxygen free radicals and NO. This leads to increased capillary permeability, and fleeting hives may form. Leucocyte migration leads...

Just as intrinsic immunity takes care of an internalized(intra-cellular) infection, each normal cell(non-professional phagocyte) is capable of  'eating' an apoptotic cell that results from environmental damage like UV radiation and mechanical shear strain and stress. Repair, including the rapid reconstitution of the cell membrane, will prevent apoptosis, following such damage. However, for the most part, it is the availability of neighboring healthy cells, which recognize the 'eat me' signal on these damaged cells, that is responsible for clearing the mess in time before the damaged cells, themselves, become toxic, as they spill out their content. More severe damage, however, will permit some of the content to fleet about and this will allow the immune cells to sense, approach and mop up the mess, at the same time suffering injuries of their own, and causing more inflammation, by virtue of their stem-cell-like fragility and inherent ability...

Every cell has an inherent ability to fight an indwelling infection. Intrinsic immunity helps fight intracellular infections that seek to maintain latency. It does so by increasing gene expression and so enabling the replication of the virus. Janus kinase(JAK), a tyrosine kinase, activated by the stress hormone, cortisol, increases gene expression by temporarily phosphorylating transcription factors and methylated bases of the DNA; activating gene expression and increasing metabolism. Cytokines for the JAK-STAT pathway activate viruses which replicate, and this leads to cell death. Active viral replication prompts this intrinsic immune response through inducing apoptosis, which is highly regulated. Arginine demethylase implicated in increased gene expression, and providing oxidative stress marker on protein Brf2, a survival protein, will inevitably lead to apoptosis. An apoptotic cell then exposes phosphatidylserine, an 'eat me' signal, that prompts phagocytosis and the elimi...

Cellular proliferation with growth is an energy-intensive and substrate-demanding process. Food availability and growth factors work together to make this happen. Metabolism is at the center of this. Glycolysis and glutaminolysis are enhanced and storage as lactic acid and malic acid helps draw on lipolysis to supply the Krebs cycle for the tissue building intermediates and NADH, FADH2 and GTP; and much more ATP therefrom, in oxidative phosphorylation. In cellular proliferative and growth states, glycolic metabolism provides steady supply of acetyl CoA, which now does not get to the mitochondria, already preoccupied with the formed acetyl CoA, from the mitochondrial beta oxidation of lipids, to form citrate and sustain the citrate cycle. The cycle then provides the metabolic building blocks and ATP for anabolism, as glycolysis is providing acetyl CoA, for lipogenesis and cholesterolgenesis, used in building the cell membrane and for the synthesis of growth steroids, as well as for hi...

Stress leads to cellular damage which necessitates frank cellular repair and growth; apoptosis, or necrosis and inflammation, that will prompt cellular proliferation and growth. For the first mechanism to happen, there must be ant-stress strategic mechanisms in place, and operational, that prevent overt damage or are rapidly mobilized to take care of the damage before cell death ensues or inflammation and cellular proliferation take place to remedy tissue deficiency. These include repair enzymes, anti-oxidants and the rapid mobilization of food resources. A well nourished body will take this path and full tissue restoration is more likely. On the other hand, apoptosis, or necrosis including necroptosis, will result if there is not enough protective mechanisms, the damage is excessive, repair is defective or nutritional resources are inadequate. Some tissue reorganization is more likely and recovery is unlikely to be full. Growth hormone and proliferative factors and co-factors...