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741Hz Cleanse Infections - Dissolve Toxins - Boost Immune System NaturallyImmune system modulation -
Master herbalists and taoist monks who studied herbs and created many of the formulas of the last 3, years had vital knowledge and practices that are invaluable for life in and beyond. They are the true gold for the human system and for the world. In TCM we always begin with a place of balance: eating nourishing foods, taking herbal formulas, moving the body until a sweat begins, drinking appropriate amounts of clean water, and delving in some sort of spiritual practice - this may on its own do a very good job of keeping the immune system in balance.
In addition to good diet and lifestyle practices, we can utilize additional aspects of modulating the immune system with adaptogenic herbs and medicinal mushrooms for adjusting the body's blood and organ functions.
They can support the body to go from a hyper-functioning state to a normal state or from an under-functioning level back to a normal state. Herbal remedies can find and fix these imbalances even when they are not obvious to us.
The practice of using adaptogenic herbs can be traced back to B. Russian toxicologist Nikolay Lazarev defined an adaptogen as a plant that increases the "state of nonspecific resistance". Said another way, adaptogens offer support to your adrenals and other body systems and structures during times of stress.
They help support mental concentration, focus, and promote a balanced response to physical or emotional stress. Medicinal mushrooms are known to be both adaptogenic in nature as well as immune modulating. Medicinal mushrooms are also safe as shown in many studies. Christopher Hobbs, Ph.
Give the liver restorative herbs and medicinal mushrooms. The liver is a key, frontline immune tissue that filters all forms of toxins.
When the liver is supported with nutritive herbs and mushrooms, it regenerates liver cells and detoxifies invaders and other debris. Formulas to take: Liver Life® , Liver Lover® or NDF Calm® - The herbs and medicinal mushrooms that modulate the liver in these formulas are made with the same organic, active ingredients in differing ratios to accommodate different types of individuals and their needs.
Formulas to take: CytoFlora® , Belly Mend® , or NDF Tummy® - The strain probiotic blend in each of these formulations has been shown to decrease gastrointestinal inflammation and leaky gut in compromised GI tracts.
The three formulas are made with the same strains of probiotics, chlorella, and other herbs with differing ratios to accommodate different types of individuals and their needs.
If the toxicity is not addressed for a prolonged period of time, the immune system is triggered. As the immune system becomes overworked, the body loses its ability to respond to invaders quickly and efficiently.
This leads to more toxic build-up and creates a cycle of poor health. It is a gentle detoxifying formula for individuals with a normal to strong constitution.
Support and modulation of the adrenal system is indispensable in the regulation of ion balances, as well as being a final site of integration for the stress response. Formulas to take: Loving Energy® - The ingredients in Loving Energy® are often used for relieving stress and exhaustion, for support of the lungs and the adrenal system.
Used by Taoist monks to replenish adrenal reserves while praying for peace on earth, this formula is equally appreciated by those who care, support, and creatively give on a daily basis. Available as a traditional alcohol tincture or alcohol free.
None of the Coronaviridae family of viruses showed an identical sequence similarity with the new coronavirus. Therefore, the virus is a novel coronavirus discovered in and its disease was formerly designated as COVID After confirmation of the novelty of the virus, the next question was, what was its origin?
SARS and MERS viruses had bats as the common origin but had different intermediary hosts to infect human beings Based on this information, the SARS-CoV-2virus was assumed to have originated and mutated in bats and used an unidentified intermediary host to cause infection in humans However, due to its novelty, we currently have minimal vaccine therapy to combatSARS-CoV-2 infection.
There is no such specific and effective treatment available for this disease, the only current option is management. The patient can be cured by supportive care which includes treatment to relieve symptoms, fluid therapy, oxygen support, and medications to support the affected vital organs In mild cases, supportive care includes medication like paracetamol to relieve symptoms like fever and body aches.
The US Center for Disease Control and Prevention CDC recommends that those who are suspected to have the disease can isolate at homes and always use face masks and gloves. People with more severe symptoms require treatment in hospitals.
Those with low oxygen levels need oxygen support and dexamethasone as it reduces the risk of death. For breathing difficulties, ventilation support and admission to an intensive care unit ICU is recommended Several antiviral and antimalarial drugs have been studied in clinical trials and recommended in emergency use in hospitals like hydroxychloroquine, ritonavir, and remdesivir.
These drugs are not recommended for early treatment Nowadays, various vaccines are available for COVID and after taking the vaccines, some countries are free of this disease. A list of vaccines is listed in Table 1. Along with that Defence Research and Development Organisation DRDO India issued a drug named 2-deoxy-D-glucose 2DG which will be used as an anti-COVID drug in India.
As far as immune response is concerned, a unique immune response has been observed in COVID patients. Recently, it was observed in a study that in normal patients, there was a lower level of classical inflammatory cytokines like G-CSF, CCL, IL-1β, IL-2, IL-6, IL, TNF-α, and TGF-β while at the same time, there was a higher plasma level of GM-CSF and CXCL in COVID patients All the observed cytokines are important components of the innate immune response.
Some scientists carried out meta-transcriptomic sequencing to analyze the innate immune cells in bronchoalveolar lavage fluid of eight COVID cases. The study reported the overexpression of pro-inflammatory genes, those of chemokines along with innate immune cells like dendritic cells and macrophages.
These studies indicated robust activation of the innate immune response in SARS-CoVinfected patients. While most of the studies have mainly focused on the innate immune response, little is discussed about the adaptive immune response Although, several studies have reported about the life cycle and heightened immune response raised by the human body against SARS-CoV-2 infection, none of the works could explain the exact mechanism.
The results of various studies on the immune system are ambiguous. The current review is an effort to unveil the viral structure, life cycle, and molecular sites that could be targeted to fight COVID infection. The study also deals with the host immune response raised against SARS-CoV-2 infection and its modulation to minimize alveolar damage.
Coronaviruses are spherical in shape diameter nm. It belongs to the β-genera of the four identified categories of coronavirus including α, β, γ, δ Among all the categories, αand βCoVs are found to infect mammals, γ-coronaviruses infect avian species, and δ-coronaviruses infect both mammals and birds The genome of the virus is comprised of positive-sense single-stranded RNA that remains encapsulated in the lipid bilayer along with capsid protein.
Daniel Wrapp and colleagues studied the structure of the spike protein using electron microscopy. They stated that the spike protein comprises three subunits i. Further, they explained that this spike protein exists in a metastable perfusion conformation that undergoes substantial structural rearrangement to fuse with the host membrane 21 It is reported that some cross-reactivity of monoclonal antibodies raised against the SARS-CoV structural proteins with SARS-CoV-2 was produced by SARS-CoV-1againstSARS-CoV-2 t is also reported that the spike protein has a furin cleavage site at the boundary of S1 and S2, which is processed before it binds with the host receptor The cross-reactivity of SARS-CoV-1 antibodies against the SARS-CoV-2 virus is also reported This furin-type cleavage was not reported in the SARS-CoV-1 virus.
From this, one can speculate why the virus has a high rate of transmission Numerous studies have reported a glycan shield over the spike protein that might be somehow helping in the immunity evasion of the virus, but further work is still needed o confirm its role in immunity evasion 28 , There is much more that needs to be discovered about this spike protein.
Once we have understood the molecular structure and spatial orientation of the protein residues of the spike protein, we can design its inhibitors accordingly The genetic material of SARS-CoV-2 is comprised of a large positive-sense single-stranded RNA that remains underneath with a nucleocapsid, which can be directly translated into viral structural and non-structural proteins and the genome of progeny virus The whole SARS-CoV-2genome consists of 29, nucleotides, which encodes amino acids, and these amino acids are used to make 27 types of proteins needed by the virus.
These new amino acids could be responsible for the extra proteins found in the SARS-CoV-2 virus. For instance, the 8a protein present in SARS-CoV-1isabsent in SARS-CoV-2, and the 84 amino acid protein 8b in SARS-CoV-1 has amino acid residues in SARS-CoV-2 The difference of these amino acids might have contributed to the production of these proteins and the high rate of transmission and immune escape.
Although little is known about these 27 viral proteins encoded by SARS-CoV-2 RNA, scientists now knows about the four major proteins encoded by the virus, which make up the major structure of the virus surface These include spike surface glycoprotein already discussed above , the small envelope protein, the matrix protein, and the nucleocapsid protein The spike glycoprotein of the newly emerged SARS-CoV-2 contains a potential cleavage site for furin proteases This observation has implications for the zoonotic origin of the virus and its epidemic spread.
The membrane of coronaviruses harbors a trimeric trans-membrane spike S glycoprotein, which is essential for the entry of virus particles into the cell The S protein contains two functional domains: a receptor-binding domain and a second domain which contains sequences that mediate fusion of the viral and cell membranes.
The S glycoprotein must be cleaved off by the host cell proteases to enable its fusion with the host ACE receptors. The S glycoprotein is necessary for viral fusion and entry into the host cells; therefore, it is also on the list to prepare a vaccine against SARS-CoV-2 Structural and molecular understanding helps researchers to correlate the innate and adaptive immune response mechanisms against SARS-CoV Here, we aim to discuss the molecular involvement of alveolar pneumocytes and the innate and adaptive immune responses toSARS-COV-2infection.
The wall of alveoli contains type-1 and type-2 pneumocytes that play an important role in the exchange of gases. Alveolar epithelium is in close proximity with blood capillaries that have the thickness of one cell, again required for an efficient exchange of gases during the phenomenon of breathing As alveolar tissue has direct access to external air, normal physiological function of pneumocytes alters in various pathological conditions like pneumonia, tuberculosis, chronic obstructive pulmonary disease COPD , acute respiratory distress syndrome ARDS , and asthma.
Reduced production of surfactant in cigarette smokers has been attributed in the pathogenesis of COPD. Cigarette smoking stimulates production of reactive oxygen species ROS which damage type-2 pneumocytes.
Damaged type-2 pneumocytes are phagocytosed by the macrophages and neutrophils that further release inflammatory cytokines and ultimately lead to the inflammation of airways which finally develops into COPD Pneumonia is another pathological condition characterized by an inflamed airway and pus-filled air sacs caused by bacterial, viral, and fungal infection of pneumocytes.
Inhaled bacteria injure alveolar cells which further releases leukotriene B4 LTB4 that acts in a chemotactic manner for the blood cells monocytes and neutrophils which rush towards the site of injury. Macrophages in response to engulfed bacteria release interleukin-1 IL-1 , IL-8, and tumor necrosis factor-α TNF-α which not only raise body temperature but also actin a chemotactic manner from immune cells.
Due to the hyper response of secreted cytokines, fluid accumulates in and around the alveoli as consolidation. Consequently, gaseous exchange becomes extremely difficult and the patient struggles to breathe 7.
ARDS is a pathological condition resulting from acute lung injury which is associated with various etiologies. Inflammation in ARDS further leads to diffuse alveolar injury, pulmonary edema, infiltration of immune cells, and formation of a hyaline membrane.
Like pneumonia, acute lung injury in ARDS also triggers the innate immune response involving macrophages, neutrophils, cytokines, and denudation of the basement membrane of the lungs followed by accumulation of fluid in the alveoli and subsequently respiratory failure Interestingly, the same types of pathological changes have also been observed in patients suffering from COVIDwhich has been discussed in depth in the preceding section.
It has been reported that the presence of ACE-2 is necessary and sufficient to initiate COVID infection It provides a gateway for COVID entry into cells and subsequently infection Therefore, it becomes necessary to study the ACE-2 enzyme and its location on all body cells.
ACE-2 is a transmembrane protein of the renin angiotensin system RAS family of proteins. It exerts its biological action by converting soluble plasma protein angiotensinogen into angiotensin-I and angiotensin-II which acts on angiotensin type-1 receptors AT1Rs and angiotensin type-2receptors AT2Rs Although significantly less information is available about their pathophysiological roles, findings from numerous studies have suggested their protective role in the heart, kidney, blood vessels, and central nervous system Scientific research suggests that the ACE-2 receptor protects the alveolar epithelium tissue present in the lung alveoli, consisting of a single layer of epithelial tissue, and enhances proliferation of type-2 pneumocytes in the case of lung fibrosis Another study suggests that well-differentiated cells are the target of COVID as it is easier to enter and egress across the plasma membrane of these cells Alveolar type-2 pneumocytes serve both these purposes.
A secondary complication of the virus infection might be due to the high distribution ofACE-2 receptors on the arteries, heart, kidneys, intestine, and lungs The life cycle of COVID is straight-forward. Once it reaches the lungs, it binds to type-2 pneumocytes of the alveoli using its spike protein At the site of the target cells, S proteins are activated by serine protease TMPRSS2, which opens the trimeric proteins into S1 and S2 proteins 20 Figure 1.
Another study confirmed that TMPRSS2 and ADAM17 intracellular proteases also helped ACE-2enable the efficient entry of the virus Heurich et al. reported that co-expression of ACE-2 with TMPRSS2 augmented SARS-S uptake.
It was reported in the study that arginine residue at and is essential for cleaving of TMPRSS2 serine proteases that mediated the viral S-protein entry S1 binds with its C-terminal on the ACE-2 receptor present on the pneumocytes which helps in its attachment.
The RNA-dependent RNA polymerase RdRp is one such non-structural protein that replaces the viral genome Remdesivir, as the inhibitor of RdRp, is currently being used in some cases to combat viral infection The viral genome replicated by RdRp and translated structural proteins like the envelope E , membrane M ,and spike S proteins are then assembled into new virions in the Golgi body.
The new virus egresses out of the cell by exocytosis Figure 1 Viral life cycle in the host cell. A healthy person gets infected when they come in contact with an infected person. Once at the surface of type-2 pneumocytes, virus has two options to gain entry into the pneumocytes. First, the virus can directly enter the pneumocytes by a fusion process and secondly by receptor-mediated endocytosis.
For receptor-mediated endocytosis, attachment with the ACE-2 receptor is a must. Host serine protease TMPRSS2 activates the spike protein and subunits S1 and S2 get separated. S1 binds to the host ACE-2 receptor while S2 initiates the fusion of the viral envelope with the host plasma membrane followed by formation of viral syncytium and entry into host cells.
Once the virus has reached inside the cell, the viral genome is directly translated into major proteins which are further fragmented into smaller proteins which are used in the synthesis of progeny virus.
The fragmented proteins are further processed in the endoplasmic reticulum and Golgi body to assemble into progeny virus. Host RNA-dependent RNA polymerase converts the viral RNA into new virions genome.
Progeny virus after completing the life cycle bursts the host cells and starts infection into nearby cells. In severely infected patients, the virus also affects the vital organs like kidneys and heart.
Potential drug targets 1. Drugs enhancing stabilization of the spike protein can prevent viral entry, 2. inhibitors of TMPRSS2 can stop activation of viral protein, 3. antibodies against S1 and S2 can prevent attachment with host ACE-2, and 4.
a fusion inhibitor can prevent viral entry. Our nonspecific immunity produces a rapid response to viral infection and acts as the first line of defense. This allows our body time to prepare the specific immunity that needs to be triggered. It is always there in our body and responds as soon as a pathogen invades our body Innate immunity involves physical and chemical barriers and includes cellular response.
Major cell types involved in this are leukocytes, neutrophils, monocytes, eosinophils, basophils, and natural killer cells While, neutrophils and monocytes carry out phagocytosis of the invaded pathogen to impart the innate cellular response, natural killer cells kill the invaded pathogen by inducing apoptosis.
Apart from this, the complement system also plays a vital role in innate immunity Innate immune response quickly responds to the SARS-CoV-2virus whenever a healthy person comes in contact with an infected person Figure 2A.
Various studies have reported these symptoms in COVID patients 52 , But viruses that escape from the mucus and cilial lining of the trachea finally reach the alveoli and enter type-2 pneumocytes As the virus replicates in these cells, patients remain asymptomatic up to two weeks post-infection.
But continuous virus replication causes a cellular injury that involves the synthesis and secretion of inflammatory mediators like leukotrienes, prostaglandin, and histamine, which make up the second line of the innate response 54 , The main goal of inflammation is to isolate, destroy, and inactivate the invader, remove debris, and repair the injured tissue.
Due to inflammation, circulating neutrophils and monocytes rush to the site of infection, where they start phagocytosis of the invading virus Figure 2 Innate immune response against SARS-CoV A Early innate immune response and development of symptoms.
Host immune response activatestype-2 pneumocytes invaded by the virus. Inflammatory cytokines IL-1, IL-6, and TNF-1α activate the macrophages. Macrophages in acute cases release small proportions of inflammatory markers that not only attract the circulatory monocytes and neutrophils at the site but also increase the body temperature.
B Delayed innate immune response and development of severe pneumonia. Circulating inflammatory mediators IL-1, IL-6, and TNF-α in blood further exacerbate the acute innate immune response by increasing the chemotactic effect of monocytes and neutrophils towards the lungs.
The monocytes and neutrophils leak out through the endothelial cells and enter into the alveoli. The second type of macrophages, i. As a result, excess fluid accumulates in the alveoli resulting in severe pneumonia. Further, these cells also secrete IL-1, IL-8, and TNF-α,enhancing the chemotactic effect of the circulating monocyte and neutrophil cells to squeeze through blood capillaries to reach the extravascular region and finally the alveoli Macrophages also secrete IL-1 and TNF-α, which act on the hypothalamus which causes high fever and acts upon the bone marrow, which causes leukocytosis Virally infected cells also produce a lot of interferons IFNs which play an essential role in innate IFN-α and β and adaptive immune responses IFN-γ Phagocytosis is followed by the formation of pseudopodia, the engulfment of the virus and the formation of the phagosome, and then a fusion of lysosome-containing vesicles which causes hydrolysis and the degradation of the ingested virus antigens.
In neutrophils, the viral antigens are finally released into the extracellular region from where they reach the lymph nodes and activate B; cells in the adaptive immune system. Along with that, if the engulfed virus is too strong to be degraded into antigens, then the neutrophils undergo self-lysis through a free radical-induced mechanism There is one more mechanism known as neutrophil extracellular traps NETS by which neutrophils can inhibit viral replication.
The nucleic material released from degraded neutrophils moves to the extracellular region, binds to the antigen with its histone protein, and causes lysis of that antigen.
Then, cathepsin-like enzymes initiate hydrolysis of the complex thus formed 60 , Monocytes have a different fate after phagocytosis. The hydrolyzing released antigens are not released into the circulation but are thoroughly processed inside the monocytes and expressed on the major histocompatibility complex-I and II.
MHC-I is expressed by all nucleated cells, but MHC-II is only presented by the antigen-presenting cells macrophages, dendritic cells, and B-lymphocytes The monocyte-derived macrophages reach the lymph nodes, which also stimulate an adaptive immune response.
The complement system is a significant player in the immune system. It further enhances microbial clearing by phagocytic cells utilizing liver complement proteins and antibodies The complement system involves the activation of a cascade of reactions with the attachment of antibodies on the antigen to form a membrane attack complex MAC , which includes a channel in the antigen cells.
Water and ions leak out from the cells, and ultimately lysis of antigenic cells takes place There are three pathways through which the complement system can act:.
Classical pathway: The pathway is initiated to bind antibodies to the antigen present on the foreign cell.
C1 is the first complement protein that attaches to the Fc part of the antibody. Subsequently, complement proteins C4, C2, C3b, C5b, C6, C7, C8, and C9 bind to each other and form a long complex. The complex breaks at the interface of C3band C5b.
The pentameric complex comprises an MAC that leads to the lysis of cells. The remaining complex acts as opsonin for the circulating macrophages and is phagocytized. Released complement C3a and C5a are acted upon by the protease released by mast cells, which are activated and augment the inflammatory response by attracting monocytes and neutrophils and further augment the inflammatory response Alternative pathway: The complement protein directly binds without an antibody with an antigen present on the foreign cell and initiates a cascade reaction that involves subsequent attachment with C5b, C6, C7, C8, and C9.
Finally, the complex breaks at the interface of C3b and C5b, and the rest of the steps are like the classical pathway Lectin pathway: The pathway starts with the binding of lectin with mannose molecules present on the antigen.
Attachment of lectin is followed by complement proteins C4, C2, C3b, C5b, C6, C7, C8, and C9. The rest of the steps are like the classical pathway Apart from the circulating complement proteins, virally infected cells produce interferons released into the extracellular region and bind with the receptors on healthy cells and stimulate them to produce degrading enzymes.
When these healthy cells get infected with the same virus, the enzymes activate and kill the invading virus. The enzymes break the viral messenger RNA and thus viral protein synthesis Further, IFNs enhance the phagocytic activity of macrophages, stimulate the production of antibodies by βcells, and enhance the killing power of natural killer cells and cytotoxic T cells Natural killer cells, a special kind of lymphocyte cells, are the next fighters of the innate immune response.
These cells kill only those cells which lack MHC-I on their surface Once they come in contact with cells, they release perforin and create pores in the plasma membrane of the invaded cells.
Consequently, ions and water rush inside the infected cell leading to cell swell and burst Unfortunately, the dysregulated innate immune response is observed in COVID patients.
A higher level of pro-inflammatory cytokines like IL-1, IL-6, TNF-α, and chemokines 6are noted in the serum of severely infected patients 71 Figure 2A. A higher number of neutrophils and a lower number of lymphocytes are also observed in the patients. Cytokines and chemokines have an essential role in the innate immune response A recent clinical report of 41 patients from the Huanan sea food market reported a high level ofIL-2, IL-7, IL, IP,Granulocyte colony-stimulating factor G-CSF , MCP-1, MIP 1-α, and TNF-α, particularly in those patients who were in the ICU The presence of IL-2 in COVID patients indicate activation of the adaptive immune response IL-7 works at all stages of T cell development Raised levels of IL-7showed that adaptive immune response is rapidly required in patients involved in the above study IL is an anti-inflammatory cytokine secreted by the regulatory T cells, macrophages, dendritic cells, Th1, and Th2 cells.
Irrespective of its source, IL inhibits the functions of macrophages and dendritic cells and limits the functions of Th1 and Th2 cells as well as that of natural killer cells It is previously reported that IL production increases dysregulated immune response as it can damage the host cells.
High expression of IL in COVID patients could be one reason behind the delayed and weak adaptive response Elevated granulocyte colony-stimulating factor G-CSF is a hematopoietic growth factor indispensable for the proliferation of and differentiation in neutrophils Higher levels of G-CSF could be the main reason behind the observed neutropenia in COVID patients IPor CXCL is a 10kDa protein secreted by leukocytes, neutrophils, eosinophils, monocytes, epithelial, and endothelial cells in response to IFN-γ, which acts upon the CXCR3 receptors present on the activated T cells, β-lymphocytes, natural killer cells, dendritic cells, and macrophages It is reported that IL plays an essential role in T cell trafficking in various infections caused by parasites like Toxoplasma gondi Monocyte chemoattractant protein-1 MCP-1 , also known as CCL-2, plays an important role in chemotactic monocytes and macrophages and has a repairing role in the damaged tissue.
The said effect of MCP-1 is already reported in previous studies Production of MCP-1 by monocytes involves the infection of monocytes with the virus, which then releases INF-β, which acts on other leucocytes.
These leucocytes secrete some unknown soluble substance that stimulates the monocytes to secrete MCP-1 protein for chemotactic purposes. The upsurged level of MCP-1 reported in the above study showed the involvement of monocytes and macrophages at the injury site due to SARS-CoV-2 Macrophage inflammatory protein1α MIP-1α or CCL-3 is the next cytokine observed in patients with SARS-CoV Various studies have reported that MIP-1α enhances leukocyte trafficking at the site of infection The movement of the leucocytes towards the injury site further augments the inflammatory response through TNF-α, IL-1, and IL Therefore, to stop further inflammatory response, inhibition of MIP-1α becomes crucial.
A study on the same has already shown reduced recruitment of neutrophils when MIP-1α was selectively inhibited by an anti-MIP-1α antibody Tumor necrosis factor-α TNF-α is the master regulator of inflammation. It is known that TNF-α contributes to inflammation by participating in vasodilation and edema formation, enhancing adhesion of leucocytes to the epithelium, regulating blood coagulation, inducing oxidative stress in inflammation, and finally by inducing fever Augmented TNF-α in the above study further evidenced the development of strong inflammation in SARS-CoV-2 patients.
Zhou et al. They observed a heightened immune response by taking samples directly from the bronchoalveolar lavage BAL instead of taking blood samples. Cell composition analysis of BAL fluid of COVID patients showed neutrophils, eosinophils, dendritic cells, and mast cells.
Interestingly, like previous studies, raised NLR was also observed in this study, which again confirms the role of NLR in COVID pathogenesis They also observed pro-inflammatory cytokines and chemokine genes IL-1B, CXCL, CXCL-8, and CCL-2 along with specific antiviral interferon-stimulating genes ISGs like IFIT and IFITM in BAL.
IFIT and IFITM genes belong to the family of genes called IFITs expressed by the infected viral cell to initiate INFs synthesis in nearby healthy cells and thus play an important role in the host innate immune response It is previously reported that IFIT-coded proteins interfere with the viral translation process and thus with the viral replication process The raised levels of INFs in COVID patients would result due to overexpression of IFIT and IFITM genes to combat viral infection in nearby healthy cells They also observed an upregulated level of calgranulin genes with pleiotropic functions in inflammatory disorders SA8, SI00A Interestingly, the upregulatedIL-1RN and SOCS3 were also observed, which confirms feedback inhibition of cytokines as both these genes have an antagonistic function on cytokine synthesis.
Among the upregulated cytokines, CXCLis observed as highly expressed in all SARS-CoV-2 patients, highlighting its role in COVID pathogenesis CXCLhas a major chemoattractant role in the mucosal tissue during cellular injury, especially in the lungs.
The chemotactic neutrophils further exacerbate inflammation by CXCL-8, CXCL, and CXCL-2 as these cytokines play a crucial role as neutrophil chemoattractants While most studies on SARS-CoV-2 shed light on the innate immune response, few studies also reported activation of the adaptive immune response in COVID patients.
A recent survey of 34 hospitalized patients evidenced the activation of humoral-mediated response part of the adaptive immune response in SARS-CoVinfected patients.
The blood antibodies, IgG and IgM levels, were carefully monitored for up to four months. It was concluded that IgG antibody level continuously kept increasing after recovery in SARS-CoVinfected patients while the blood level of IgM first increased and then kept on decreasing.
This study evidenced the activation of B cells producing specific antibodies against SARS-CoV-2antigens Another study was carried out by Eugenia Ziying Ong and colleagues, who reported a high-level expression of IL-1 in severe cases of SARS-CoV-2 A similar study was conducted using the blood samples of COVID patients.
The severity of infection was described based on cytokines IL-6, IL-8, and IL in cellular microparticles cMPs. These cMPs were reported to contain cellular receptors, cytoplasmic proteins, nucleic acids RNA, micro-RNA, and DNA , and cytokines.
A high number of cMP was written in the blood of COVID patients compared to that of healthy persons. Upon cytokine analysis, a higher level of IL-6, IL-8, and IL was detected in severe pneumonia patients. Low levels of IL-6 secreted by macrophages can protect the lung alveoli.
Still, the excessive release of IL-6 can adversely affect them by inducing fibrinogen activation and activation of coagulation factors, inhibit endothelial repair, and thus increase the permeability of blood vessels which causes inflammatory lung injury.
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Download references. This work was supported in part by the Marble Center for Nanomedicine, the Ragon Institute of MGH, MIT and Harvard, the NIH awards CA, EB, UCA, AI, AI, AI and CA to D.
and the Mark Foundation for Cancer Research. This material is based upon work supported in part by the US Army Research Office through the Institute for Soldier Nanotechnologies at MIT, under Cooperative Agreement Number WNF is an investigator of the Howard Hughes Medical Institute. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA. Howard Hughes Medical Institute, Chevy Chase, MD, USA.
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Abstract Therapies modulating the immune system offer the prospect of treating a wide range of conditions including infectious diseases, cancer and autoimmunity. Key points In immunotherapy, choosing the right target cell, tissue and treatment duration is essential to ensure effective immunomodulation while avoiding toxicity.
Reducing biomaterial complexity is essential to facilitate clinical translation. Macroscale biomaterials strategies for local immunomodulation Article 23 April Design of therapeutic biomaterials to control inflammation Article 28 February Biomaterials to enhance adoptive cell therapy Article 26 January Introduction Modulating the immune system is a pivotal treatment strategy of modern medicine.
Full size image. Targeting lymphoid organs Lymphoid organs coordinate the maturation and migration of immune cells while organizing and regulating immune responses Fig. Principles of lymph node targeting Passive targeting of therapeutics to lymphatic vessels Lymph nodes interface with peripheral tissues through lymphatic vessels, which drain lymph fluid from all tissues and provide a conduit for immune cell trafficking.
Table 1 Ongoing clinical trials of immune cell- and tissue-targeted biomaterials therapeutics Full size table. Targeting circulating leukocytes Many immune cells continuously recirculate between secondary lymphoid organs, blood and tissues, patrolling for foreign antigens. Targeting tissue-resident cells Some innate and adaptive immune cell populations permanently reside in tissues and provide functions such as immediate immune defence at barrier tissues, local production of protective antibodies and tissue-resident immune memory.
Delivery at mucosal barriers Several immune cell populations reside at mucosal barriers, such as the skin, the airways, and the gastrointestinal and reproductive tracts. Outlook Biomaterial-mediated targeting of immune cells and tissues is starting to have clinical impact, with great promise for the future of vaccines and immunotherapies.
Box 1 Defining optimal immune cell targets for disease modulation Modulation of the immune system can only be effective if the targeted cells and their responses are well understood.
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With Low-calorie desserts Pomegranate salad recipes of simple techniques like Sustainable energy source Recovery supplements, meditation and repeated eystem to modulatio you can modulatikn the autonomic nervous system and inhibit the response of modulatipn immune mosulation. Researchers from mImune Radboud university medical Immune system modulation have provided the first scientific evidence for this in an article published in the scientific journal PNAS. A well-functioning immune system protects our body from pathogens. But sometimes the immune response is too pronounced or persistent. This can lead to the development of autoimmune diseases such as rheumatism. Our immune system is controlled, amongst other things, by the autonomic nervous system, which is involved in the 'fight-or-flight response'. It was always thought that we could not voluntarily influence either the immune system or the autonomic nervous system. Thank mdoulation for Healthy respiratory system nature. You ssystem using a Pomegranate salad recipes version with limited support for CSS. To obtain the best experience, we recommend you use a more up modupation date Antioxidant and digestive health or turn off compatibility mode in Immume Explorer. In the meantime, Pomegranate salad recipes Immuns continued support, we are displaying the site without styles and JavaScript. Therapies modulating the immune system offer the prospect of treating a wide range of conditions including infectious diseases, cancer and autoimmunity. Biomaterials can promote specific targeting of immune cell subsets in peripheral or lymphoid tissues and modulate the dosage, timing and location of stimulation, thereby improving the safety and efficacy of vaccines and immunotherapies. Here, we review recent advances in biomaterials-based strategies, focusing on targeting of lymphoid tissues, circulating leukocytes, tissue-resident immune cells and immune cells at disease sites.
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