Safe Immunity
Phagocytic degradation of microbes and apoptotic microbe-infested cell is a much safer and effective way of combatting infections. This is the ultimate goal of acquired, specific immunity. Otherwise, necroptosis and necrosis result in non-specific events outside the controlled and protective environment of the phagolysome inside the phagocyte. The extent of degradation is dependent on the opsonization of the usually toxic antigens. Toxic antigenic material will damage the phagolysosomal membrane, the plasma membrane and cause the premature dumping of microbes out of the cell. Hence, even cytokines, which are intrinsically toxic, like TNF, and aid in inflammation, and by extension, in the influx of leucocytes, will prevent effective phagocytosis.
Normally, opsonizing antibodies promote safe and effective phagocytosis, and cytotoxic T-cells, that promote apoptosis of infected host cells, help in enclosing the potentially toxic content of the dying cells in apoptotic sacs for safe and effective phagocytosis. This means that, in most cases of specific immunity, the infection is fought and contained without the host showing obvious signs of the disease.
So, in non-specific immunity, where inflammatory cytokines are released, leukocytes while carrying phagocytosis, will inevitably degranulate from the 'leakage' of granules due to membrane dysfunction or destabilization. This will cause more damage to host cells and further inflammation, and when inflammation continues unabated, we will come to a point where phagocytosis will not take place anymore. The leaked hydrolases, out of the leucocytes to the exterior of the host cells, are at best, moderately effective in killing microbes, in the presence of interstitial enzyme deactivators.
On the contrary, host cells lack the protective coats that microbes which normally will survive in a much harsher environment in the wild have. This scenario will help spread the infection throughout the body, instead. This is especially true for superantigens(toxins secreted by microbes), which promote polyclonal T cell activation and massive cytokine release. If inflammation is survived, T cell deletion or anergy occurs.
The IL-4 and IL-10 downregulate the production of IFN-gamma, MHC Class II, and costimulatory molecules on the surface of APCs. These effects produce memory cells that are unresponsive to antigen stimulation. MHC crosslinking also activates a signaling pathway that suppresses hematopoiesis and upregulates Fas-mediated apoptosis. This will lead to a carrier state and, once more, promote the spread of infections. Neutrophil migration, independent of T cell activation, is characteristic. HIV, Staphylococcus infections produce superantigens. Eczema, psoriasis, scarlet fever, toxic shock syndrome, diabetes, nasal polyps and rheumatic fever have been associated with superantigens.
The microbial genes that regulate superantigens regulate M protein and capsule production. It is thought that these have evolved to counter immunity.
The question arises: How can exercise or general activity help fight or ward off infections? The answer lies in the fact physical activity increases tissue perfusion and leucocyte migration through the influence of basal homeostatic(non-inflammatory) chemoattractant and inflammatory cytokine-induced chemokine release. Additionally, there is membrane--both lysosomal and plasma membrane-- stabilization by steroids, released during exercise. Together with the exercise-linked cytokine release and activation, this will promote effective phagocytosis with little risk of degranulation.
The cytokines(TNF, IL1, IL8) with external factors such as LPS and viruses that promote the in situ synthesis and release of leukotrienes and other chemokines which also cause degranulation, help home in leucocytes upon damage call. They are said to be pro-inflammatory. They will cause fever and pain through prostaglandin release, modulated by steroids. Basal chemokines do not elicit or get released by inflammation.
Dr. Oliver Verbe Birnso, MD.
Normally, opsonizing antibodies promote safe and effective phagocytosis, and cytotoxic T-cells, that promote apoptosis of infected host cells, help in enclosing the potentially toxic content of the dying cells in apoptotic sacs for safe and effective phagocytosis. This means that, in most cases of specific immunity, the infection is fought and contained without the host showing obvious signs of the disease.
So, in non-specific immunity, where inflammatory cytokines are released, leukocytes while carrying phagocytosis, will inevitably degranulate from the 'leakage' of granules due to membrane dysfunction or destabilization. This will cause more damage to host cells and further inflammation, and when inflammation continues unabated, we will come to a point where phagocytosis will not take place anymore. The leaked hydrolases, out of the leucocytes to the exterior of the host cells, are at best, moderately effective in killing microbes, in the presence of interstitial enzyme deactivators.
On the contrary, host cells lack the protective coats that microbes which normally will survive in a much harsher environment in the wild have. This scenario will help spread the infection throughout the body, instead. This is especially true for superantigens(toxins secreted by microbes), which promote polyclonal T cell activation and massive cytokine release. If inflammation is survived, T cell deletion or anergy occurs.
The IL-4 and IL-10 downregulate the production of IFN-gamma, MHC Class II, and costimulatory molecules on the surface of APCs. These effects produce memory cells that are unresponsive to antigen stimulation. MHC crosslinking also activates a signaling pathway that suppresses hematopoiesis and upregulates Fas-mediated apoptosis. This will lead to a carrier state and, once more, promote the spread of infections. Neutrophil migration, independent of T cell activation, is characteristic. HIV, Staphylococcus infections produce superantigens. Eczema, psoriasis, scarlet fever, toxic shock syndrome, diabetes, nasal polyps and rheumatic fever have been associated with superantigens.
The microbial genes that regulate superantigens regulate M protein and capsule production. It is thought that these have evolved to counter immunity.
The question arises: How can exercise or general activity help fight or ward off infections? The answer lies in the fact physical activity increases tissue perfusion and leucocyte migration through the influence of basal homeostatic(non-inflammatory) chemoattractant and inflammatory cytokine-induced chemokine release. Additionally, there is membrane--both lysosomal and plasma membrane-- stabilization by steroids, released during exercise. Together with the exercise-linked cytokine release and activation, this will promote effective phagocytosis with little risk of degranulation.
The cytokines(TNF, IL1, IL8) with external factors such as LPS and viruses that promote the in situ synthesis and release of leukotrienes and other chemokines which also cause degranulation, help home in leucocytes upon damage call. They are said to be pro-inflammatory. They will cause fever and pain through prostaglandin release, modulated by steroids. Basal chemokines do not elicit or get released by inflammation.
Dr. Oliver Verbe Birnso, MD.
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