Triggering an Immune Response

An allergen is usually an inert substance (e.g. pollen, house dust mite faeces) that in some individuals can trigger the generation of an (inappropriate) antigenic response. Mediated by TH2 lymphocytes, it causes B-Lymphocytes to produce lgE. Subsequent exposure of a sensitized individual to the allergen is therefore able to cross-link IgE antibodies on the surface of mast cells and trigger an immune response and histamine release. 

Based on the above principles, it might be assumed that a therapeutic protein obtained by direct extraction from human sources (e.g. some antibody preparations) or produced via recombinant expression of a human gene/cDNA sequence (e.g. recombinant human hormones or cytokines) would be non-immunogenic in humans whereas foreign therapeutic proteins (e.g. non-engineered monoclonal antibodies) would stimulate a human immune response. This general principle holds in many cases, but not all. So why do therapeutic proteins of human amino acid sequences have the potential to trigger an immune response Potential reasons can include ... 

Many proponents allege that homeopathic products resemble vaccines because both provide a small stimulus that triggers an immune response. This comparison is not valid. The amount of active ingredients in vaccines is much greater and is measurable. Immunizations produce measurable antibodies, but ultradilute homeopathic products have no measurable active ingredients and produce no measurable response. In addition, vaccines are used preventively, not for curing symptoms. 

Any substance capable of triggering an immune response is called an antigen. Antigens... 

PUVA is most useful for the treatment of severe psoriasis. Early (patch and plaque) stage cutaneous T-cell lymphoma (CTCL) also responds to PUVA therapy. In addition, patients in advanced stages of CTCL have been treated with a modification of PUVA known as extracorporeal photopheresis. In this therapy, blood from a CTCL patient who has taken psoralen is exposed to UVA light and returned to the patient. Lymphocytes are altered or destroyed by the treatment, and theoretically, the return of these abnormal cells triggers an immune response directed against certain lymphocyte surface antigens. The effectiveness of this modality appears to be variable. 

In the second type of interaction, the components of the immune system are active participants in that the xenobiotic or some fraction of a xenobiotic is recognized as nonself and therefore provides the driving force for the response. Drugs and chemicals which are capable of triggering an immune response are generally low-molecular-weight substances possessing some inherent reactivity. For the most part, the xenobiotic... 

Autoantibodies are also useful in prognosis and monitoring of disease. Elevated levels of autoantibodies to p53 are associated with a poor prognosis, independent of the tumor-related antigens. This may be due to the fact that expression of the tumor antigen at a distant and/or abnormal site triggers an immune response. The titer of the autoantibodies also tends to follow the amount of tumor antigen, which... 

Immunogenicity has attracted enormous attention recently, and this will be a key decision point for competitors to evaluate whether their molecule meets the criteria, or not. With regard to the reactions that may occur in products that are biotechno-logically driven, these results are not clearly understood. For example, changes in the manufacturing process may alter the nature of the finished product and trigger an immune response. A noteworthy case of this was centered on Johnson Johnson s EPO product which is currently marketed under the brand-name Eprex . 

The fact that a local, transient expression of a foreign protein is enough to trigger an immune response. 

These strategies enhanced the efficacy of pDNA-based vaccines but may have the theoretical drawback of triggering an immune response against the self-protein used as fusion. Such an immune response would lead to autoimmune disorders targeting the immune system. 

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