Intrinsic Immunity
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 elimination of the microorganism. Phosphate and calcium are the key to phagocytosis. A fail-apoptosis leads to necroptosis, and, together with necrosis(cell permeability with lack of caspase activation and cytochrome c release) that occurs in severe damage, is characterized by cell swelling and bursting, that promotes inflammation and the spread of an infection.
Increased and controlled(regulated) gene expression requires an abundance of nutrients and metabolic co-factors(calcium, phosphate, NAD, citrate, acetate). Oxygen uptake--stimulated by citrate and malate--must be adequate for oxidative phosphorylation and optimal ATP production.
Regulated stress and the ensuing minor inflammation are good for immunity. In brief stress, the body is able to mobilize resources to cater for cell metabolism, the 'fright and flight response' and bolster the immune system, all at the same time. But in chronic stress, many genes will be overexpressed, leading to damage and inflammation, then shut down in an attempt to quell the inflammation; the result of the exhaustion of cellular maintenance resources. The way this is achieved is through tyrosine phosphorylation, followed by DNA hypermethylation that silences many genes, notably those for growth factors(with the resultant receptor down-regulation), in spite of the presence of, and even as a result of an increased amount of a stimulatory ligand like cortisol or a cytokine. Cell death will result from overstimulation. Tyrosine(required by JAK) transport is a sign of distress.
Good nutrition, that provides for ATP, optimal cell metabolism, repairs, heat shock(protein folding)proteins and anti-oxidation, will kill internalized microbes following phagocytosis(internalization); and through the ensuing membrane-protected tissue degrading autophagy, which is fundamentally a repair-oriented survival mechanism. Hence autophagy prevents inflammation and provides a much safer form of immunity.
There are many ways in which intrinsic immunity may become deregulated: an overwhelming infection that over-activates and exhausts the immune system and depletes nutritional resources; too much stress and inflammatory stimuli derived from an infection that mobilize nutritional resources, intensively activate and work the immune system to the point of nutritional exhaustion and ultrastructural damage; inadequate nutrients--to start with-- needed to feed the system, cause repair and prevent inflammation; difficult-to-access pathogens that require supplementary effort to get mobilized, say, in the bone and epidermis; and too much nutrition that is sufficient to wake up a latent infection but inadequate to contain it.
Degranulation, which causes collateral damage to host cells-- as opposed to well contained degradation by phagocytosis--is the corner stone of a deregulated immunity.
Dr. Oliver Verbe Birnso, MD.
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 elimination of the microorganism. Phosphate and calcium are the key to phagocytosis. A fail-apoptosis leads to necroptosis, and, together with necrosis(cell permeability with lack of caspase activation and cytochrome c release) that occurs in severe damage, is characterized by cell swelling and bursting, that promotes inflammation and the spread of an infection.
Increased and controlled(regulated) gene expression requires an abundance of nutrients and metabolic co-factors(calcium, phosphate, NAD, citrate, acetate). Oxygen uptake--stimulated by citrate and malate--must be adequate for oxidative phosphorylation and optimal ATP production.
Regulated stress and the ensuing minor inflammation are good for immunity. In brief stress, the body is able to mobilize resources to cater for cell metabolism, the 'fright and flight response' and bolster the immune system, all at the same time. But in chronic stress, many genes will be overexpressed, leading to damage and inflammation, then shut down in an attempt to quell the inflammation; the result of the exhaustion of cellular maintenance resources. The way this is achieved is through tyrosine phosphorylation, followed by DNA hypermethylation that silences many genes, notably those for growth factors(with the resultant receptor down-regulation), in spite of the presence of, and even as a result of an increased amount of a stimulatory ligand like cortisol or a cytokine. Cell death will result from overstimulation. Tyrosine(required by JAK) transport is a sign of distress.
Good nutrition, that provides for ATP, optimal cell metabolism, repairs, heat shock(protein folding)proteins and anti-oxidation, will kill internalized microbes following phagocytosis(internalization); and through the ensuing membrane-protected tissue degrading autophagy, which is fundamentally a repair-oriented survival mechanism. Hence autophagy prevents inflammation and provides a much safer form of immunity.
There are many ways in which intrinsic immunity may become deregulated: an overwhelming infection that over-activates and exhausts the immune system and depletes nutritional resources; too much stress and inflammatory stimuli derived from an infection that mobilize nutritional resources, intensively activate and work the immune system to the point of nutritional exhaustion and ultrastructural damage; inadequate nutrients--to start with-- needed to feed the system, cause repair and prevent inflammation; difficult-to-access pathogens that require supplementary effort to get mobilized, say, in the bone and epidermis; and too much nutrition that is sufficient to wake up a latent infection but inadequate to contain it.
Degranulation, which causes collateral damage to host cells-- as opposed to well contained degradation by phagocytosis--is the corner stone of a deregulated immunity.
Dr. Oliver Verbe Birnso, MD.
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