Antigen, Antibody and Lymphocytic White Blood Cell Recruitment

The most important point to be considered is that the Thymosin Alpha 1 is tolerated well and does not over-stimulate the production of cytokines. Another advantage of this agent is that unlike the other similar agents such as interleukin-2 and interferon-alpha, this agent is not responsible for any kind of toxicities or side effects and hence, is considered as safe.

For treating cancer and immunodeficiency patients, Thymosin Alpha 1 was undergone Clinical Trials, which demonstrated that the agent enhances the responsiveness of the immune system, is not toxic and also augments the functioning of specific lymphocytes which includes the maturation of T cells, T cell-mediated cytotoxicity, production of antibiotics and lymphoproliferative responses to mitogens.

The other functions include the increased activity of the Natural Killer Cells, increase in the level of cytotoxic T cells and the expression of Th1 type cytokines is also increased.

During the development of the T cells, selected antigens are expressed sequentially. This depicts the pathway of the differentiation of the T cells from the stem cells in the bone marrow to the maturation of thymocyte in the thymus, ultimately causing the diversion of the helper CD4+ cells and the CD8 cytotoxic suppressor cell sublineages and these are then further differentiated in the peripheral lymphoid tissues.

The experiments conducted in human thymocytes and mouse cells have shown that the Thymosin Alpha 1 can cause a reduction in the apoptosis of the immune cells. These experiments have also shown that in the immunosuppressed mice, stem cell expansion was increased. In addition to this, the expression of the thymopoetic cytokines IL-15, IL-7 and IFN-alpha was also observed increasing by the Thymosin Alpha 1.

The effectiveness of the Thymosin Alpha 1 can be explained by the different immunological effects where an enhanced or stimulated immune response is needed for health outcomes, in cases like cancers and bacterial, fungal and viral infections and also in cases where the immunocompromised subjects like individuals with renal failure or the elderly people, are vaccinated. Tumors and the cells infected with the virus were killed when the CD8 cytotoxic Tc1 cells, CD4 helper Th1 cells and NK cells acted in cooperation with each other. The killing of fungal and bacterial infections and the anti-tumor and anti-viral responses were also provided by the activated Dendritic Cells. Another effect of the activated Dendritic Cells was an enhanced efficiency in the presentation of the antigen, so as to increase the antibody production. This particular effect of the Thymosin Alpha 1 is more important in those immunocompromised elderly individuals, who are unable to respond effectively to vaccination.

The molecules with the ability to stimulate the immune responses are called as Antigens. Due to the difference in the epitopes or the surface features, every antigen gives a specific response. The immune system’s B cells produce the Y-shaped proteins, which are known as Antibodies or Immunoglobulins, in response to the antigen’s exposure.

Different experimental models demonstrated that Ta1 was successful in the amelioration of intestinal inflammation and respiratory allergy, by promoting treg cells and inducing IDO1. Hence, the immunomodulatory and the therapeutic properties of Ta1 can also include the maintenance of diplomatic relations between microbial communities and mammals.

The regulatory T cells’ producers, FoxP3 IL-10, increase as a result of the IDO stimulation. This increase results in cytokine production’s feedback inhibition, thereby suppressing the response of the immune system to avert a storm of pro-inflammatory cytokines and the autoimmune phenomena.

Exogenous and/ or endogenous TLR agonists may undergo collaborative interactions which may result in novel reciprocal trends of the surveillance of the immune system and the effector mechanisms helping in the safe disposal of the pathogens which may help in the effective prevention of tissue injury and the excessive inflammatory responses.

Enhancing Immunosurveillance

Thymosin Alpha 1 disables the virus’s immune system cloaking techniques by boosting the production of MHCs. In addition to modulating the expression of cytokines and activating the immune effector cells, T1 also exerts direct effects on the target cells. It can increase the visibility of the viral antigens to the immune system by increasing their expression on the surface of target infected cells, depressing the viral replication and thereby decreasing their ability to escape the immune surveillance.

Experiments have shown that Ta1 tends to increase the protein expression on the surface of tumor cells or virally infected cells and also the ones that mediate the presentation of the antigens like the beta 2 microglobulin, MHC Class 1, MHC Class 2 as well as the antigens specific to tumors. The downregulation of the antigen-presenting molecules is thought to be the reason for the immune escape by the tumor cells and the virally infected cells.

Partially Restored Mucociliary Clearance, i.e., the Cilia clearing the Mucus

As a response to the treatment with Ta1 and the CFTR modulating drugs, a partially restored ciliary beating was detected by the multi DDM.

HAEC’s were obtained from the three varied subjects homozygous for the F508del/ F508del mutation in CFTR and were further treated with Ta1 in the concentration of 100 ng/ml for the duration of 48 hrs and comparison was made with the same cells which were treated with the vehicle only control. The partial restoration of the normal ciliary beating dynamics was indicated by the decrease in the coordination length scale due to the treatment with all three drugs. The results were consistent with the role of these drugs reported earlier in modulating the CFTR functionality in CF cells.

Evidence of ACE Inhibition combating Viral Pneumonia by Boosting ACE2

It was determined that Tha1 shows inhibitory effects on angiotensin-converting enzyme. Examination of the inhibition pattern and the kinetic parameters like Km and Vmax was done. Maximum inhibition pattern was displayed by Tha1 when analyzed on the basis of the Lineweaver Burk plot. 3.33 µM and 0.8 µM were the values for Ki and IC50 of Tha1 respectively. The interaction of Tha1 with ACE enzyme (C- and N- domains) due to the hydrogen, hydrophobic and electrostatic forces, was indicated by molecular docking. The binding of Tha1 to ACE domains was suggested by molecular modeling and it was demonstrated that the binding was with a higher affinity to N- domain with the binding energy of -22.87 kcal/mol.

Teh study included human patients infected with viral pneumonia and an association was demonstrated with an improved outcome in the patients who continued the use of ACEi during viral pneumonia. In cases of viral pneumonia from H7N9 influenza virus pneumonia, the importance of ACE2 was demonstrated in an animal study (in mice) and published in scientific reports, which showed the worst pathology and survival in ACE2 KO mice. The results thereby demonstrated the potential benefits of ACE2 in viral-mediated lung injury presumably from the removal of generation of Ang 1-7 and Ang II.

Thymosin alpha 1 stimulates the endothelial cell migration, angiogenesis and wound healing

An enhancement of the morphological differentiation of endothelial cells was shown by Tha1, which is a 28 amino acid peptide isolated initially from the thymus. It was also shown that Tha1 is a potent chemoattractant for the monocytes and endothelial cells in vitro. In a subcutaneous model (in vivo studies), Tha1 was shown to stimulate angiogenesis. In a punch model, when Tha1 was administered through i.p. or topically, the wound healing was accelerated, which demonstrated that Tha1 promotes wound healing and angiogenesis.

Synergy from Combining Thymosin Alpha 1

IFN-α2b alone was compared with the combination of IFN-α2b and Tha1. One trail showed that after a duration of 6 months, 71% of the patients receiving combination therapy had normal serum ALT levels while only 35% of the patients receiving IFN-α2b alone showed normal serum ALT levels. 65% of the patients treated with combination therapy showed the clearance of Hepatitis C Virus RNA while the same was demonstrated in only 29% of the patients treated with IFN-α2b alone.

Powerful Anti Oxidation

The intracellular Glutathione (GTH), which has important antiviral effects and shows the direct inhibition of the in vitro growth of cancer and virally infected cells, increases after Tha1 treatment. Highly efficient effects of Tha1 were shown to eliminate superoxide radicals when compared with the antioxidant assays.

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