Suppressing the Immune Response

Suppressing the Immune Response Preventing the Action of T Cells 

Muromonab (Orthoclone OKT3 ) is a mouse monoclonal antibody that kills T lymphocytes, cells that are a part of the immune response. Muromonab, the first monoclonal antibody approved for use as a drug, is used to treat rejection of a donated kidney, liver, or 

A type of interferon produced by white blood cells, alpha interferon, has been engineered and produced to keep the progression of hepatitis C virus, a serious liver infection, under control. The first alpha interferons were slightly modified forms of natural interferon alpha produced in E. coli. More recent versions, peginterferon and 

Etanercept (Enbrel ) is an engineered protein that combines the tail of an antibody with a part of the receptor for tumor necrosis factor (TNF). TNF is one of the cell-damaging proteins involved in inflammation. It got its name because the first thing scientists discovered that it did was kill cancer cells. Killing cancer cells is only one of its skills, however, and that may be something that happens 

Vaccines made with recombinant proteins marshal an immune response to specific viruses to treat or prevent disease. Vaccines to prevent infection with the liver-damaging hepatitis viruses (Twinrix , Recombivax HB , and Engerix-B ) include a recombinant version of a hepatitis virus B protein. Recombinant hepatitis B protein is also included in some combination vaccines given to children. Comvax also includes a recombinant flu virus protein. 

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T-suppression. Ts cells may be activated more effectively than TH cells, thereby suppressing the immune response. 

Mechanisms by Which Ultraviolet Radiation, a Ubiquitous Environmental Toxin, Suppresses the Immune Response... 

Mechanisms by Which Ultraviolet Radiations Suppresses the Immune Response 263... 

As mentioned above, the early studies of Kripke found that exposure to sub-carcinogenic doses of UV radiation suppresses the immune response of recipient mice and allows for the progressive growth of transplanted UV-induced regressor tumors.2 Adoptive transfer of antigen-specific T lymphocytes78could transfer the immune suppression to normal syngeneic recipient mice. 

The generator was initially used to provide Pb-212 to make radioactive liposomes for immune suppression (11). The objective of these studies was to suppress the immune response prior to organ transplant. The first studies were performed with lead-212 in nonantigenic liposomes in rats in order to measure nonspecific... 

It is relevant to explain the use of the letters CD as a prefix to monoclonal antibodies. Lymphocytes possess many different surface proteins, each of which possesses many distinct epitopes. To classify these lymphocyte antigens, a numbering system has been established that clusters molecules having similar epitopes. Thus, all monoclonal antibodies that detect the epitopes on a single antigen are assigned to a numbered cluster of differentiation (CD). In most cases a defined CD denotes a protein of specific function. For example, the protein called CD4 is associated with cells (lymphocytes) that help the immune response, while CD8 is found on cells that suppress the immune response. 

Mechanism of Action. The basis for the antiar-thritic effects of penicillamine is unknown. Reductions in serum immunoglobulin M-rheumatoid factor have been observed with penicillamine, and this drug has been shown to depress T-cell function.53 These and similar findings suggest that penicillamine works by suppressing the immune response in rheumatoid arthritis, but the exact mechanisms remain to be determined. 

Clinical Use. Cyclophosphamide (Cytoxan, Neosar) is an anticancer alkylating agent that is commonly used in a variety of neoplastic disorders (see Chapter 36). This drug may also be helpful in suppressing the immune response in certain autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.12 43 High doses of cyclophosphamide are also used to prevent tissue rejection in patients receiving bone marrow transplants and other organ transplants. 

Clinical Use. Mycophenolate mofetil (CellCept) is primarily used to prevent or treat organ rejection following cardiac and renal transplantation. This drug is typically combined with other immunosuppressants (cyclosporine, glucocorticoids) to provide optimal immunosuppression in patients receiving these transplant types.39,40,70 Mycophenolate mofetil may also be useful in suppressing the immune response associated with autoimmune conditions such as systemic lupus erythematosus.2... 

Clinical Use. Sulfasalazine (Azulfidine, other names) has unique properties, with some antibacterial characteristics similar to sulfonamide drugs (see Chapter 33) and some of anti-inflammatory characteristics similar to the salicylates (see Chapter 15). This drug is primarily used to suppress the immune response associated with rheumatoid arthritis and inflammatory bowel disease.38,61... 

Skin cancer is the most common type of cancer. Damage to skin DNA from sunlight is the most common cause of skin cancer. This causes mutations that result in formation of cancer cells and that suppress the immune responses that normally prevent replication of such cells. The class of chemicals most commonly associated with causing skin cancer are the polycyclic aromatic hydrocarbons from sources such as coal tar. These can be metabolized to electrophilic substances that bind with DNA to initiate cancer (see Figures 7.3 and 8.3). Arsenic in drinking water has been established as a cause of precancerous lesions, called arsenical keratoses, and squamous cell carcinoma of skin. 

Immunosuppressants are substances that suppress the immune response. Inhibition or neutralization of the major part of the body s defence system is essential in (7.) organ transplantation and (2.) autoimmune diseases. The following are considered to be some of the most important immunosuppressants ... 

ManLAM and PILAM seem to have opposite effects on the immune response [262,264]. Man-LAM was shown to inhibit macrophage activation, the production of the pro-inflammatory cytokines IL-12 and TNF-o and, M. tuberculosis -induced macrophage apoptosis. PILAM, in contrast, induces the release of pro-inflammatory cytokines. By suppressing the immune response, ManLAM thus promotes survival of pathogenic mycobacteria, while PILAM promotes killing of non-pathogenic mycobacteria. ManLAM and PILAM were also shown to interact with different cell-surface receptors on phagocytic cells [262,264]. 

A major drawback of lipoplex is the production of inflammatory cytokines. We have shown that Kupffer cells in the liver are the major source of inflammatory cytokines after intravenous injection of lipoplex.44 A functional depletion of Kupffer cells resulted in less cytokine production after lipoplex injection into mice. Macrophages and DCs can be considered the source of cytokines, because they produce large amounts of cytokines following incubation with lipoplex composed of plasmid DNA.45 To suppress the immune response, the depletion of CpG sequences from plasmid DNA is a promising option. Yew et al.46 eliminated 270 of 526 CpG dinucleotides in a reporter plasmid DNA, either by eliminating nonessential regions... 

Dendritic cells (DC) and macrophages exposed to live microfilariae in vitro show rednced matnration after M. tuberculosis infection, indicating a compromised activation of the immune system by mycobacteria upon co-infection with helminths (Talaat et al. 2006), thereby possibly reducing the susceptibility of DC for infection by M. tuberculosis. Thus, in vitro studies indicate that helminths can suppress the immune response to mycobacterial infections. However, the in vivo relevance of in vitro findings has to be more intensively examined. 

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