Heterologous immunity: Immunopathology, autoimmunity and protection during viral infections

Vaccination and heterologous immunity: educating the immune system

“…The mechanisms of heterologous immunity can vary, but the focus of this review is on experimental systems where both beneficial and detrimental heterologous immunity are mediated by crossreactive T cells. 22,23 More than 20 years of research have delineated basic principles of heterologous immunity, such as (1) T cell crossreactivity is quite common between unrelated pathogens and alters T cell immunodominance; 24 (2) networks of crossreactive T cells alter the efficacy of the T cell response and influence protective immunity and immunopathology; [25][26][27][28][29][30] (3) T cell crossreactivity can lead to narrowing of the T cell repertoire and generation of viral escape mutants; 31 (4) the private specificity of crossreactive T cells can determine an individual's disease outcome in regards to protective immunity and immunopathology; [31][32][33] (5) heterologous immunity can reduce the effectiveness of vaccines due to immunodominant skewing of undesired T cell responses; 29,34 (6) peptide-dependent interventions or cytokine Transactions of the Royal Society of Tropical Medicine and Hygiene blocking therapy can be used to prevent severe pathology caused by heterologous immunity; 25,30,34 and (7) the immune response to each new pathogen impacts the frequencies, distributions and activities of memory T cells to previous infections. 22,35,36 The contention is that heterologous immunity is the norm, not the exception, but given the diversity in human genetics, MHC and infection histories, is it too complicated an issue to address?…”

“…[24][25][26][27][28][29][30][31][32][33][34][48][49][50][51][52][53] For example, in the C57BL/6 mouse (H2 b ), CD8 T cell crossreactive epitopes have been defined between LCMV and Pichinde virus (PICV), LCMV and vaccinia virus (VACV), LCMV and murine cytomegalovirus (MCMV), LCMV and IAV, IAV and MCMV, and PICV and VACV, and complex networks of mouse or human T cell crossreactivity can exist between two viruses. 23,24,27,28,34,[54][55][56] Furthermore, structural studies on crossreactivity between LCMV and VACV epitopes can pinpoint the target of crossreactivity and render the OVA SIINFEKL epitope crossreactive with LCMV by an amino acid substitution. 57,58 Crossreactivity is an essential feature of TCR, and the positive selection of T cells in the thymus is mediated through self-peptides that crossreact with a substantial repertoire of foreign epitopes.…”

Identification of Three Novel CTL Epitopes within Nucleocapsid Protein of Hantaan Virus

“…During acute PUUV infection, the kinetics of the PUUV-specific tetramer-positive T cells and the PUUV-specific T cells that produced IFN-c in vitro were sharply different (19). CTL causes either pathology or virus control, possibly due to differences in viral proteins (5), HLA haplotypes (12), and altered efficiency of T-cell responses as a consequence of heterologous immunity (15), but only few CTL epitopes restricted by HLA-A1, A2.1, and B51 have been identified for HTNV (8,20), which limited the investigation of protective or pathologic immune responses against HTNV infection. In this article, we screened a panel of overlapping peptides spanning the sequence of the HTNV nucleocapsid protein for those that can stimulate IFN-c responses by ex vivo ELISPOT, and then determined the HLA context of the T-cell responses by in vitro ELISPOT.…”

Estudio temporal de diabetes mellitus tipo 1 en Chile: asociación con factores ambientales durante el período 2000-2007

“…Por el contrario, el foco del virus influenza más importante de la población santiaguina se asoció con una baja frecuencia de la enfermedad. En conjunto, ambos factores podrían estar relacionados en el contexto de un "ambiente especial" asociado a una posible alteración de la homeostasis inmune en individuos susceptibles [26][27][28] .…”