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Immune System Components that MA-8789 is Known to Stimulate:

-    CD4+ T Lymphocytes
-    CD8+ T Lymphocytes
-    CD4+CD8+ double-positive T Lymphocytes
-    CD4+CD25+ T Lymphocytes
-    CD8+CD25+ T Lymphocytes
-    CD2 
-    CD28+ NK Cells
-    γδ+ T Lymphocytes
-    γδ+CD25+ T Lymphocytes
-    Dendritic Cells
-    IgM+ B Lymphocytes
-    Interferon Gamma (IFN- γ)
-    Tumor Necrosis Factor Alpha (TNF-α)

 CD stands for “cluster of differentiation” and is used for identifying the molecules present on white blood cells. For example, CD4+ is commonly used as an identifying marker for helper T cells. The “+” designation means that the molecule is expressed on the surface of the cell. The CD molecules are commonly receptors or ligands used in cell signal transduction, but can also serve other purposes such as cell adhesion. 

CD4+ T Lymphocytes

 CD4+ is commonly used as an identifying marker for helper T cells, also known as T4 cells. Helper T cells do not directly fight infection or kill pathogens; they instead coordinate other cells of the immune system. CD4 is a glycoprotein co-receptor and recognition of antigen bound to MHC class II molecules activates the CD4 T cell. Upon activation, the T cell releases cytokines that influence the activity of many other cell types, such as macrophages, cytotoxic T cells, and B cells. HIV and AIDS are characterized by a depletion of helper T cells, which leaves the body vulnerable to many opportunistic infections. 

     There are several different subsets of effector CD4 T cells. 
-    The TH1 subset activate macrophages to kill the intravesicaluar pathogens and provide help to B cells to make antibodies
-    The TH2 subset respond to parasites and help in antibody production, associated with high levels of neutralizing antibodies
-    The TH17 subset produces the pro-inflammatory cytokine interleukin 17 and amplifies acute inflammation at sites of early infection

CD8+ T Lymphocytes

 CD8+ is commonly used as an identifying marker for cytotoxic T cells, also known as T8 cells. Cytotoxic T cells directly kill tumor cells, pathogen-infected cells, or cells that are otherwise damaged or dysfunctional. They cause apoptosis (programmed cell death) using the release of cytotoxins, such as perforin, granzymes, and granulysin. CD8 is a glycoprotein co-receptor and recognition of antigen bound to MHC class I molecules activates the CD8 T cell. 

CD4+CD8+ double-positive T Lymphocytes

 The function of CD4+CD8+ double-positive (DP) T cells is still poorly understood, but they have been observed to be differentiated effector memory cells with antiviral functions. DP T cells may also be crucial in cancer immunotherapies due to their participation in the immune response to tumors in vivo.

CD4+CD25+ T Lymphocytes

 CD4+CD25+ Treg cells are known to regulate the immune response by inhibiting proliferation of other T cell populations once infection has been contained and limit immunopathology, resulting in a protective role in several autoimmune syndromes. In mice, they have been shown to protect against colitis, diabetes, Experimental Allergic Encephalomyelitis (EAE), and lupus (SLE). Defective Treg cells have been seen in autoimmune diseases such as multiple sclerosis and autoimmune polyglandular syndrome type 2. There is much evidence supporting the role regulatory T cells play in preventing autoimmunity.

CD8+CD25+ T Lymphocytes

 Nonregulatory CD8+CD25+ T cells are potent memory T cells of great diversity in old age. Naïve T cells can no longer be regenerated into old age, so the CD8+CD25+ T cell population may be an integral part of the immune response in elderly persons. CD8+CD25+ T cells also often exhibit a CD4+CD8+ double-positive phenotype. 

CD2

 CD2 is a cell adhesion protein that is expressed in high levels on activated effector T cells and NK cells. The adhesion property of CD2 allows T cells to bind more effectively to antigen-presenting cells. CD2 also acts as a secondary co-stimulator for T cells and NK cells, due to T cells may requiring two signals for full activation (the primary signal being antigen-specific through T cell receptor interaction with MHC molecules). 

CD28

 The CD28 cell-surface protein is a co-stimulatory receptor for naïve T cells which binds to co-stimulatory ligands on specialized antigen-presenting cells. In order to fully activate a naïve T cell, both antigen and co-stimulatory ligands on the same antigen-presenting cell must be engaged. This ensures that T cells are only activated in response to an infection.

γδ+ T Lymphocytes

 A majority of T cells (including helper T cells and cytotoxic T cells) express the αβ T-Cell-Receptor chains, but a small subset of T cells do possess the γδ T-Cell-Receptor chains and are not fully understood. The γδ T cells span a wide variety of functions in both innate and adaptive immunity. They play a role in innate immunity in that they can use pattern recognition to molecules commonly associated with pathogens, and they play a role in adaptive immunity in that they can rearrange T-Cell-Receptor genes to produce recognition of a diverse array of specific antigen and develop a memory phenotype. They are also capable of phagocytosis.

Dendritic Cells

 Dendritic cells phagocytotic immune cells that bridge the gap between the innate and adaptive immunity in that they are antigen-presenting cells that activate T cells. They can communicate directly with other cells, for example through B7 interaction with CD28 on T cells, and can also communicate at a distance using cytokines. They are called dendritic cells even though they have no relation to neurons because they have branched projections that look like dendrites. 

IgM+ B Lymphocytes

 IgM+ B cells are B cells that express the immunoglobulin-M. Immunoglobulins are also known as antibodies. Immunoglobulin-M, or IgM, is physically the largest antibody produced by human B cells and is the first to respond to initial exposure to an antigen.  

 B cells are an essential component of the humoral immune response and adaptive immune system. B cells produce antibodies, with each B cell making only one type of antibody against a specific antigen. B cells generally wait inactively in lymph nodes until they are activated by their particular antigen, and then the B cell will proliferate and produce plasma cells, which produce large amounts of antibodies, and memory cells, which stay in the lymph nodes to wait for future re-exposure to the same antigen. 

Interferon Gamma (IFN-γ)

 IFN-γ is a cytokine and a class II interferon produced by effector CD4 TH1 cells, CD 8 T cells, and NK cells. The primary function of IFN-γ is the activation of macrophages. 

 IFN-γ therapy is currently FDA approved for treating chronic granulomatous disease (CGD) and osteopetrosis. 
-    CGD, also known as Bridges-Good syndrome or Quie syndrome, is a disease in which phagocytes of the immune system are unable to produce the superoxide radical that is used to kill ingested pathogens. A common hallmark of CGD is severe recurrent bacterial and fungal infections. 
-    Osteopetrosis, also known as Albers-Schonberg disease, is when osteoclasts fail to resorb bone and thus causes bone to harden and become denser and more brittle. Nerve entrapment syndrome due to pressure caused by the extra bone could result in blindness, facial paralysis, and deafness. Other complications include anemia, stunted growth, deformity, narrowing of the bone marrow, and more. 

Tumor Necrosis Factor Alpha (TNF-α)

 TNF-α is a cytokine that regulates immune cells and is produced by macrophages and T cells. TNF-α promotes the inflammatory response, is able to induce apoptosis, and inhibits tumorigenesis and viral replication. Disregulation of TNF-α has been implicated with cancer. 

 The international nonproprietary name for recombinant TNF-α is tasonermin and is used as an immunostimulant, which helps the body fight cancer. It has been used in conjunction with melphalan, a chemotherapy drug, for the treatment of soft tissue sarcoma of the arms and legs.
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