Tolerance

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Tolerance monday:

Tolerance monday Eman youssif

The ability of an antigen to elicit immune responses is called immunogenicity, which can be humoral and/or cell-mediated immune responses. Differentiation has to be made between wanted and unwanted immunogenicity. Wanted immunogenicity is typically related with vaccines, where the injection of an antigen (the vaccine) has to lead to an immune response against the pathogen (the virus, bacterium or substance). Unwanted immunogenicity is when the organism mounts an immune response against an antigen which is undesired. Unwanted immunogenicity is strongly linked with a therapeutic protein. A fraction of the patient treated with those drugs mount anti-drug-antibodies, which leads to inactivation of the drug and in rare cases to adverse effects. Immunogenic potency of antigens :

The ability of an  antigen  to elicit immune responses is called  immunogenicity , which can be  humoral  and/or  cell-mediated  immune responses. Differentiation has to be made between wanted and unwanted immunogenicity. Wanted immunogenicity is typically related with  vaccines , where the injection of an antigen (the vaccine) has to lead to an immune response against the pathogen (the virus, bacterium or substance). Unwanted immunogenicity is when the organism mounts an immune response against an antigen which is undesired. Unwanted immunogenicity is strongly linked with a  therapeutic protein . A fraction of the patient treated with those drugs mount anti-drug-antibodies, which leads to inactivation of the drug and in rare cases to  adverse effects . Immunogenic potency of antigens

Proteins are significantly more immunogenic than polysaccharides. T cell response is required to drive immunogenicity. Since lipids and nucleic acids are non-immunogenic haptens, they require conjugation with an epitope such as a protein or polysaccharide before they can evoke an immunologic response. Proteins or polysaccharides are used for studies of humoral immune response. Only proteins can serve as immunogens for cell-mediated immunity. :

Proteins  are significantly more immunogenic than  polysaccharides . T cell response is required to drive immunogenicity. Since  lipids  and  nucleic acids  are non-immunogenic  haptens , they require  conjugation  with an  epitope  such as a protein or polysaccharide before they can evoke an immunologic response. Proteins or polysaccharides are used for studies of humoral immune response. Only proteins can serve as immunogens for cell-mediated immunity.

In the rush to deliver novel biologics to market, developers have, on occasion, overlooked factors that contribute to protein immunogenicity. In addition, autologous or human-like proteins have proven to be surprisingly immunogenic in some applications, suggesting that assumptions about immune tolerance, too, require careful consideration in biologics design. Fortunately, years of thorough study of the parameters influencing vaccine efficacy allow parallels to be drawn for protein therapeutics. Factors including delivery route, delivery vehicle, dose regimen, aggregation, innate immune system activation, and the ability of the protein to interface with the humoral (B cell) and cellular (T cell) immune systems, all impact the potential immunogenicity of vaccine immunogens when delivered to humans (for reviews related to unwanted immunogenicity determinants, see references below). Like vaccines, protein therapeutics can engender both cellular and humoral immune responses. Anti-drug antibodies (ADA) may neutralize the therapeutic effects of the drug and/or alter its pharmacokinetics. T cells are certainly involved in this immune response when IgG class ADA are observed, because antibody isotype switching is a hallmark of T-dependent antigens. More serious adverse events can be provoked if ADA cross-react with a critical autologous protein. Examples of adverse ADA responses include autoimmune thrombocytopenia (ITP) following exposure to recombinant thrombopoietin, and pure red cell aplasia, which was associated with a particular formulation of erythropoietin (Eprex). Since the impact of immunogenicity can be quite severe, regulatory agencies are developing risk-based guidelines for immunogenicity screening. :

In the rush to deliver novel biologics to market, developers have, on occasion, overlooked factors that contribute to protein immunogenicity. In addition, autologous or human-like proteins have proven to be surprisingly immunogenic in some applications, suggesting that assumptions about immune tolerance, too, require careful consideration in biologics design. Fortunately, years of thorough study of the parameters influencing vaccine efficacy allow parallels to be drawn for protein therapeutics. Factors including delivery route, delivery vehicle, dose regimen, aggregation, innate immune system activation, and the ability of the protein to interface with the humoral (B cell) and cellular (T cell) immune systems, all impact the potential immunogenicity of vaccine immunogens when delivered to humans (for reviews related to unwanted immunogenicity determinants, see references below). Like vaccines, protein therapeutics can engender both cellular and humoral immune responses. Anti-drug antibodies (ADA) may neutralize the therapeutic effects of the drug and/or alter its pharmacokinetics. T cells are certainly involved in this immune response when IgG class ADA are observed, because antibody isotype switching is a hallmark of T-dependent antigens. More serious adverse events can be provoked if ADA cross-react with a critical autologous protein. Examples of adverse ADA responses include autoimmune thrombocytopenia (ITP) following exposure to recombinant thrombopoietin , and pure red cell aplasia, which was associated with a particular formulation of erythropoietin ( Eprex ). Since the impact of immunogenicity can be quite severe, regulatory agencies are developing risk-based guidelines for immunogenicity screening.

http://www.jstor.org/discover/10.2307/30106034?uid=2&uid=4&sid=21102693347391:

http://www.jstor.org/discover/10.2307/30106034?uid=2&uid=4&sid=21102693347391

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