In simple terms INFEPERIUM™ is a Biological Response Modifier (BRM) / Immunomodulator that helps reset the immune system so your body can heal itself. It addresses in an endogenous (from inside the body) way the majority causes of Chronic Disease and their effects on the body.
The active ingredient in INFEPERIUM™ modulates both the adaptive and innate immune systems (without negative side effects) and allows the body to eliminate chronic inflammation, a major cause in all diseases. This is the same active ingredient that is in our USDA approved immunomodulator.
INFEPERIUM™ restores proper cell signaling, pathogen recognition and proper cell energy, Adenosine Triphosphate production (ATP) endogenously.
INFEPERIUM™ is a major breakthrough in Immunotherapy. The action of INFEPERIUM™ is to modulate both the innate and adaptive immune systems that have been degraded and compromised due to disease, environmental, bacterial, viral etc. to normalization and homeostasis allowing the bodies own healing and defense mechanisms to restore proper cell signaling, proper cellular respiration versus fermentation, regulation of cellular transport, and healing. INFEPERIUM™ embodies the latest and most medically accepted theories and practices of immunotherapy, which is now at the forefront and becoming the standard of care for chronic diseases which include cancer, a wide range of autoimmune conditions, and most importantly addressing the growing concern of bacterial resistance.
What INFEPERIUM™’s breakthrough Immunotherapy can do, and why it is different.
INFEPERIUM™’s immunomodulator is one of the few molecules, if not the only one known today, that affects and modulates both the innate and adaptive immune systems without negative side effects.
The primary triggers for Chronic Disease are:
The establishment of a state of Chronic Inflammation (CI), which is now considered the main cause of the vast majority of disease.
Due to the prolonged state of CI, improper and aberrant cellular signaling begins which is the harbinger of most AutoImmune(AI) conditions.
This state of cellular "Misinformation" creates over and under reaction of the immune response and inhibits the bodies defense mechanisms from properly functioning. This includes but is not limited to depressed CD4 and CD8 counts.
Suppressed MHC I and MHC II, which Marshall the forces of T cells, B cells, NK cells and various Macrophages, that prevent pathogens from invading the bodies systems or once they have attacked them to consume and destroy them. Most importantly interfering with the Jak-Stat signaling pathway which controls immune deficiency syndromes and most Cancers.
These three states determine the vast majority of disease. However, if you can address these above states of disease from an Endogenous state, you are going to able to reverse a vast number of diverse conditions that are created by these altered states of health. As well as bringing the patient to Homeostasis.
INFEPERIUM™ addresses these altered states by the modulation of the bodies cytokine cascade from attacking healthy cells to reversing GI and inducing proper cell signaling and pathogen recognition. That it modulates and reestablishes proper function of the innate and adaptive immune systems and responses is the key to the unique effectiveness of INFEPERIUM™.
The Science
Why Biologics?
According to the United States Food & Drug Administration (FDA) “Biological products include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues. Biologics are isolated from a variety of natural sources - human, animal, or microorganism - and may be produced by biotechnology methods and other cutting- edge technologies. Gene-based and cellular biologics, for example, often are at the forefront of biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available.”
According to the FDA, how do biological products differ from conventional drugs?
“In contrast to most drugs that are chemically synthesized and their structure is known, most biologics are complex mixtures that are not easily identified or characterized. Biological products, including those manufactured by biotechnology, tend to be heat sensitive and susceptible to microbial contamination. Therefore, it is necessary to use aseptic principles from initial manufacturing steps, which is also in contrast to most conventional drugs.”
Again, according to the FDA, “Biological products often represent the cutting-edge of biomedical research and, in time, may offer the most effective means to treat a variety of medical illnesses and conditions that presently have no other treatments available.”
Therefore, Biologic response modifiers (BRMs) can improve or modify the body's natural response to infection and disease. BRMs, a drug class of their own, are the newest medications which are based on compounds made by living cells, not synthetic drugs which the body naturally attempts to reject which frequently leads to injury of major organs like the liver and kidneys.
Biological response modifiers (BRMs) are substances that modify immune responses. They can be both endogenous (produced naturally within the body) and exogenous (from outside the body, as pharmaceutical drugs), and they can either enhance an immune response or suppress it.
Some of these substances arouse the body's response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy (therapy that makes use of immune responses), which can be helpful in treating many diseases, such as cancer (where targeted therapy often relies on the immune system being used to attack cancer cells) and in treating autoimmune diseases (in which the immune system attacks the self), such as some kinds of arthritis and dermatitis.
Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors (e.g., CSF, GM-CSF, G-CSF). "Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body's natural defense mechanisms against cancer”, whereas BRMs for rheumatoid arthritis aim to reduce inflammation.
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Immunotherapy and Immunomodulators:
Immunotherapy is the treatment of disease by inducing, enhancing or suppressing an Immune Response. Jedd Wolchok MD summed up Immunotherapy just last year in response to Immunotherapy being Science Magazines 2013 Breakthrough of the Year. “10 years ago Immunotherapy was almost in the category of snake oil. A few years ago it was stated that Immunotherapy can work. Now Immunotherapy has entered the main stream.”
James T. Allison, Phd and professor and Chair of Immunology at the MD Anderson Cancer Research Institute (CRI) has received the prestigious Tang Prize, the Louisa Gross Horwitz Prize and the Harvey Prize, all in 2014 for his work on CTLA-4 as an antibody inhibitor in many treatment resistant cancers with amazing survival statistics. Work in CTLA-4 & PD-1 also called “immune check point therapies” are the only two presently approved FDA ImmunoTherapy agents so far.
Why Immunotherapy?
Specificity. T-cells recognize peptides, which are short chain biological molecules that are produced by every cell category including virus, bacteria, cancer/mutations. T-cells can recognize them and can destroy them, and most importantly they have the following two important elements.
First, Memory. As T-cells destroy pathogens, which are biological or environmental invaders which produce abnormal cells, they go through 3 phases: expansion, contraction and memory.
- Expansion is when the T-cells multiply to overwhelm the attacker
- Contraction is when they diminish due to program cell death after the attacker is neutralized.
- Memory is a multiplication of cells that remember the genetic code of the attacker. Memory cells proliferate and circulate through the body standing ready to attack.
Second, Adaptability. Cancerous tumors, viruses and bacteria, can mutate and alter themselves in order to evade various medical therapies. Cancer alone has 9 resistant mechanisms used to trick, hide and survive. So called present “Standard of Care Therapies” which use in large measure synthetically produced drugs frequently harmful to the body, but can’t adapt fast enough to counteract and destroy the mutation capabilities of cancer cells, bacteria and viruses. However, T-cell antigen receptors can. They adapt and respond as quickly as the pathogens, because they can combine and alter themselves as many 10 to the 15th power in different combinations. The stimulation of the T-cells is a natural response of the body’s immune system to the injection of INFEPERIUM™. This is the key to why and how of immunotherapy.
Immunomodulators:
An immunomodulator is a substance that either suppresses or activates the body's immune response. These substances are separated into two groups: immunosuppressants and immune activators. Immunosuppressants inhibit the body’s natural immune response, while immune activators generally condition or reprogram it to target a specific disease-causing agent.
Immunomodulators can be produced in synthetic form or naturally in the body. Cytokines are examples of innate immune mediators. Synthetic versions are available in either immunosuppressant or immune activator forms. A suppressant immunomodulator works by inhibiting the activation of critical immune system agents such as calcineurin and the formation of thymus cells (T-cells) and antibodies. In comparison, an activating immunomodulator uses the process of adaptive immunity to recondition lymphocytes and T-cells to kill known pathogens or tumor cells.
Cyclosporine and methotrexate are commonly used synthetic immunosuppressors. Methotrexate is used in patients with autoimmune ailments. Lupus and rheumatoid arthritis are examples of autoimmune disorders that cause the patient's body to attack his or her own cells. Eventually the targeted cells and tissue become damaged after repeated attacks.
The process of organ rejection is similar to autoimmune dysfunction, except the immune system targets the transplanted organ rather than the body’s own cells. Organ transplant recipients take suppressant drugs such as cyclosporine, tacrolimus and sirolimus to prevent organ rejection. Nearly all transplant recipients, except a rare few, must adhere to a strict daily regime that involves taking these medications for life. Not taking the medications as prescribed will almost always induce organ rejection, which could lead to death. Due to the medication’s toxic side effects, immuno-suppressors should only be used in cases of severe autoimmune dysfunction or organ transplantation.
Immunomodulators that activate the immune system include vaccines and cancer immunotherapy. Vaccines work by exposing the patient to weakened or inactive forms of certain bacteria and viruses. The immune system then adapts by producing antibodies that are programmed to immediately kill the introduced pathogen once it re-enters the body, which is called adaptive immunity.
Cancer immunotherapy is very similar to pathogen vaccination. The difference between the two therapies is the agent in which adaptive immunity is induced. Vaccines use microorganisms, while cancer immunotherapy uses microorganisms and enhanced immune cells. Microorganism-based cancer immunotherapies are used to combat some forms of cervical and liver cancers caused by viruses. A cell-based immunomodulator, on the other hand, uses enhanced immune cells such as cytotoxic T lymphocytes (CTLs), dendritic cells (DC) and natural killer cells (NK cells) to target and destroy the patient’s cancerous cells.
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What can INFEPERIUM™’s breakthrough immunomodulators and biological response modifiers do? And why are they different?
INFEPERIUM™’s active ingredient is one of the few molecules that affects and modulates both the innate and adaptive immune systems without negative side effects.
INFEPERIUM™’’s immunomodulators and biological response modifiers can therapeutically treat the following conditions and more:
- Chronic Plaque Psoriasis
- Recalcitrant Diabetic Wounds
- Primary Progressive MS (Multiple Sclerosis) and other Demyelinating Neuropathies and other Neurological conditions
- Chronic Pain
- Chronic AutoImmune Diseases
- Various Hard-Treat Cancers
Actions Addressed by INFEPERIUM™’s immunomodulators and biological response modifiers
I. Inflammation
- Preserving Acute inflammation which is necessary for healing, restoration and defense against invading pathogens.
- Reducing Chronic inflammation which is the beginning of the reversal of degenerative disease.
II. Restores proper Cell Signaling
- Through cytokines, cell messenger pathways, cellular communication and transduction.
- Reverses aberrant, dysregulated, disrupted, error altered, confused and distracted communication.
III. Acts as an Adjuvants or Adjunct
- Help regulate and restore the proper on/off switches of immune cascade proteins and cell activity, especially Apoptosis (programmed cell death).
- This will amplified proper cell activity, messaging and signal routing
The Adaptive Immune System
Adaptive immunity is a person's defense system built on specific cellular targeting. It takes time for the immune system to develop its weaponry (up to 96 hours after infection), but ultimately the adaptive response is far more effective because of its precision.
Once infection is identified, antigen is transported to lymphoid organs where it is recognized by naive B and T cells. Clonal expansion and differentiation of these cells occurs, and then the battle begins. The immune system can take several tacks, depending on the type of infection encountered. Ultimately, the goals of the adaptive response are two-fold: to produce neutralizing antibody, and to flag up infected cells for destruction. This annihilation can be carried out by the cells of both innate and adaptive immunity.
Actions of the Adaptive Immune System
Adaptive immunity is stimulated by the generic actions of innate immunity. Once a foreign organism is identified by the innate immune system, circulating T-cells begin interacting with foreign antigen. Based on their encounter, they can do one of three things: they can kill infected cells directly, they can boost the actions of macrophages to kill infected cells, or they can return to lymph tissue to incite a B cell response.
Stimulated B cells will proceed to produce antibody, which can then circulate to fight the infection.
Antigen Recognition
"Antigen" refers to the parts of a foreign organism recognizable by the adaptive immune system. Typically, these are structural proteins, such as the spike proteins of viruses. Antigens can be huge, and are more often identified by epitopes, or smaller fragments of the folded proteins. As such, a single antigen can be recognized by multiple antigen receptors. Antibody has evolved to recognize a dizzying array of antigen epitopes. Antigen can be picked up by lymphocytes in the lymph tissues (T cells and B cells) or the blood stream (T cells only).
T cell receptors (TCR) recognize antigen fragments (that is digestion products) on the surface of cells, whereas B cell receptors (BCR) bind whole antigen in the extracellular fluid. T cells only "see" antigen when it is presented by MHC (Major Histocompatibility Complex) on the cell surface. Antigen digestion and presentation is one of the major functions of the dendritic cells (circulating monocytes) and macrophages. These are referred to as Antigen-Presenting Cells (APCs).
Naive B-cells express IgD and IgM on their cell surfaces, which bind antigen as it is washed into lymph tissue with the afferent lymph fluid. Antigen is presented to B cells by follicular dendritic cells (FDCs), which are also classed as APCs. FDCs can endocytose antigen directly from the afferent lymph or receive them from CD4+ T-cells.
Cellular response: Proliferation and Differentiation
• T cell response
Once T cells recognize antigen presence in the tissues, they go into action. Their first response is always to recruit help, which is accomplished by returning to the nearest lymph node to carry out clonal expansion. Daughter T cells are created with identical TCRs in order to recognize the identified antigen. These daughter cells are then returned to the circulation via the efferent lymph.
T cells can differentiate three different ways, based on their Cluster of Differentiation (CD) number. All T cells are CD3+, and naive circulating T cells will differentiate upon interaction with antigen to become either CD8+ (cytotoxic) or CD4+ (helper) T cells. CD4+ T-cells will initially become CD4-TH0 cells, and must differentiate to TH1 or TH2 depending on the whim of the adaptive response. TH1 and TH2 cells carry out different types of responses: TH1 is responsible for enhancing the macrophage response, whereas TH2 cells enhance the B cell antibody production. Typically, animals produce a balanced response of TH1 and TH2 cells, though this can lead to pathology, as can a skewed response, depending on the nature of the foreign organism.
• B cell response
Naive B cells recognize antigen in the lymph tissue when it is presented to them by Follicular Dendritic Cells (FDCs). They also undergo clonal expansion, creating a germinal center in the follicle as they develop and mature into plasma cells. Once mature, plasma cells in the lymph node migrate to the medullary cords and begin secreting antibody into the efferent lymph. Antibody eventually reaches the circulation in order to wage war on the intruder.
Tools of the Adaptive Immune System
Antigen Presenting Cells
• Macrophages
• Interdigitating Dendritic Cells
◦ Only IDCs can incite a primary response in naive T-cells
• CD4+ Tcells
• B-cells
Antigen Binding Molecules
• Immunoglobulins
• T-cell Receptor (TCR)
• Natural Killer (NK) Cells
Adaptive Immunity to Viruses
Humoral
• Production of neutralizing antibody
• Antibody-dependent cell mediated cytotoxicity (ADCC)
Antibody-labelled cells can be targeted by NK Cells as another defense against viral infection. Antibody produced against viral protein can attach to infected cells during their budding phase, which effectively labels them for NK targeting. NK cells express Fcγ receptors with which to detect such cells. Once activated, they release a host of enzymes to induce apoptosis of the budding cell.
Cell-Mediated
• CD8+ T-cell mediated killing of virus infected cells
◦ Main cells involved in the immune response to intracellular virus infection
◦ Recognition of MHC I-peptide complex
◦ Infected cells are killed by apoptosis
▪ Perforin and granzymes activate the caspase cascade
▪ Fas-ligand triggers the Fas-mediated apoptosis pathway
▪ Cytotoxic cytokines (especially TNF-α & TNF-β lymphotoxin) act on TNF receptors to induce programmed cell death
Adaptive Immunity to Bacteria
• The adaptive and innate responses work together to destroy bacteria
• The adaptive response ensures the innate response is carried out efficiently
Humoral
• Complement activation of the classical pathway
◦ Production of IgM and IgG makes the complement system more efficient
Cell-Mediated
• Help for macrophages
◦ IgG production (T-helper type II cells and B cells) which improves phagocytosis by opsonisation
◦ Infected macrophages are rescued by T-helper type I cells when phagocytosis and digestion mechanisms fail to eliminate the pathogen
Extracellular Infection
• Complement and phagocytosis
• B cell and T helper type II cell stimulation
• Production of IgM which activates the classical cascade
• Class switching of IgM to IgG which is a good opsonin and targets bacterial Fcγ receptor expressed by macrophages and neutrophils
Vesicular Infection
• The infected macrophage secretes IL-12
• IL-12 stimulates T-helper type I cells which release IFN-γ
• IFN-γ triggers the macrophages to kill the pathogens inside
The Innate Immune System
The innate immune system is the first barrier of defense to infection. It relies on an older, more generic, and faster acting set of tools than the adaptive system. While the adaptive system is essential for a specific response to infection, it is ultimately the innate system that conquers foreign attackers through means of phagocytosis.
Non-specific protective mechanisms include such innate factors as:
• Physical barriers
◦ Skin
◦ Ciliated mucous membranes
◦ Commensal organisms
• Humoral factors
◦ Lysozyme
◦ Complement
◦ Interferons
• Cellular mechanisms
◦ Phagocytosis
• Factors which regulate species specificity
◦ Membrane receptors for pathogens
◦ Nutritional requirements
◦ Temperature
◦ pH
• Mechanisms of innate immunity are always present and generally unchanging
• Adaptive immunity is acquired only on contact with the infectious agent (antigen) and therefore does not function before first contact with the antigen
Actions of the Innate Immune System
Recognition of Microorganisms
• The innate immune system recognizes components of pathogens which are intrinsically foreign (i.e. not present on normal mammalian cells), such as:
◦ Lipopolysaccharides of gram-negative bacteria
◦ Peptidoglycans of gram-positive bacteria
◦ Mannose sugars
◦ D-isoform amino acids
• These are given away as foreign by expressing pathogen-associated molecular patterns (PAMPs)
• PAMPs are recognized by pattern recognition receptors (PRRs) expressed on mammalian cells
◦ Pattern recognition receptors are expressed on many different cell types, not just on phagocytes
◦ Not all are expressed by all cells: different cell types express a different range of PRRs
◦ PRRs are either intracellular, membrane-associated or soluble:
▪ Recognition of pathogens via the cellular PRRs results in phagocytosis and inflammation
▪ Recognition of pathogens via the humoral PRRs results in various killing mechanisms
• Engagement of PRRs by PAMPs triggers:
◦ Phagocytosis
◦ The expression of cytokines, which brings about inflammation and other immune responses
