Bystander antigens

One likely reason for the prevalence of helminths is their undoubted ability to down-regulate the host immune system at both the antigen-specific and polyclonal levels [3], In many chronic diseases, such as schistosomiasis and lymphatic filariasis, peripheral blood T cells show dramatically impaired parasite antigen-specific responsiveness [4], as discussed in more detail below. Moreover, from early reports of immunosuppression in animal models of infection, to studies in Africa linking vaccine failure to heavy helminth infection, there is clear evidence that infections can diminish reactivity to bystander antigens, particularly with increasing intensity of... 

Recent modifications include the use of reporter antigens in the popliteal lymph node assay (Albers et al., 1997 Gutting et al., 2002a). Reporter antigens can be regarded as bystander antigens, and the response to reporter antigens can be determined fairly easily... 

Together, these findings indicate that oral exposure to the drugs may induce T cell responses to bystander antigens, such as reporter antigens or maybe autoantigens. The latter needs to be proven in future experiments. 

Lavelle EC, McNeela E, Armstrong ME ct al. Cholera toxin promotes the induction of regulatory T-cells specific for bystander antigens by modulating dendritic cell activation. J Immunol 2003 171(5) 2384-2392. 

Direct activation of T cells (e.g., derived from patients) Cell damage (reactive oxygen species, apoptosis, necrosis) LLNA (topical application, indication of hapten-protein conjugation) Oral exposure studies (using bystander or reporter antigens to read out immunosensitization)... 

R17. Rovere, P., Vallinoto, C., Bondanza, A., Crosti, M. C., Rescigno, et al., Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function. J. Immunol. 161, 4467-4471 (1998). 

The requirement of multifunctional peptide complexes is perhaps most obvious for the development of subunit peptide vaccines. Successful immunizations with peptide antigens cannot be achieved without the inclusion of a bystander T-helper cell determinant in the chemical entity (4) or in the immunizing cocktail (5). For outbred animals and humans, multiple peptide epitopes, representing determinants of more than one major histocompatibility complex (MHC) proteins, are used to overcome subunit vaccine unresponsiveness, and this also improves antigen presentation in inbred animals (6). 

Another critical determinant in the cascade of events leading to MS lesion development is antigen presentation. Antigen presenting cell (APC)/T-cell activation involves at least four major processes (1) Molecular mi mi cry, (2) Epitope spreading, (3) Bystander activation, and (4) Cryptic antigen... 

Bystander activation activation of autoreactive cells through nonspecific inflammation and induction of inflammatory cytokines and chemokines is also of pathological consequence in MS. It has been suggested that bystander activation, induced by persistent virus infection or primed by molecular mimicry may activate autoreactive T-cells specific for the CNS (McCoy et al., 2006). Einally, cryptic antigens may also play a role in immune activation. In other immune-mediated diseases such as Chronic Lymphocytic Thyroiditis and Chagas Heart Disease, exposure of cryptic epitopes leads to the activation of autoimmune cells and further contributes to... 

Thus, this mechanism appears to permit individual T cells to express their primary function of antigen recognition and cytokine release, but limits their responses to a single-hit , thus minimizing the potential risk of local bystander tissue damage via a locally expanding T cell response. 

Another type of reaction that may affect the formed elements in blood is the innocent bystander reaction. With this type of reaction, antigen-antibody complexes formed in blood adhere nonspeciflcally to cells. Complement is then activated, resulting in ceU lysis. 

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