Heterologous immunity: Immunopathology, autoimmunity and protection during viral infections

Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Autoimmunity (Impact Factor: 2.71). 06/2011; 44(4):328-47. DOI: 10.3109/08916934.2011.523277
Source: PubMed


Heterologous immunity is a common phenomenon present in all infections. Most of the time it is beneficial, mediating protective immunity, but in some individuals that have the wrong crossreactive response it leads to a cascade of events that result in severe immunopathology. Infections have been associated with autoimmune diseases such as diabetes, multiple sclerosis and lupus erythematosis, but also with unusual autoimmune like pathologies where the immune system appears dysregulated, such as, sarcoidosis, colitis, panniculitis, bronchiolitis obliterans, infectious mononucleosis and even chronic fatigue syndrome. Here we review the evidence that to better understand these autoreactive pathologies it requires an evaluation of how T cells are regulated and evolve during sequential infections with different pathogens under the influence of heterologous immunity.

Download full-text


Available from: Liisa K Selin, Apr 09, 2015
  • Source
    • "Indeed, CD8 T cells are essential regulators of viral infection, playing important roles in the clearance of virus-infected cells and sometimes causing damaging immunopathology (1). The relative balance between protective immunity and immunopathology often determines the fate of the virus-infected host (2). A classic example is that of lymphocytic choriomeningitis virus (LCMV), where the same clone of T cells responsible for viral clearance can mediate a severe leptomeningitis if the virus is replicating in the brain (1, 3). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The balance between protective immunity and immunopathology often determines the fate of the virus-infected host. How rapidly virus is cleared is a function of initial viral load, viral replication rate, and efficiency of the immune response. Here, we demonstrate, with three different inocula of lymphocytic choriomeningitis virus (LCMV), how the race between virus replication and T cell responses can result in different disease outcomes. A low dose of LCMV generated efficient CD8 T effector cells, which cleared the virus with minimal lung and liver pathology. A high dose of LCMV resulted in clonal exhaustion of T cell responses, viral persistence, and little immunopathology. An intermediate dose only partially exhausted the T cell responses and resulted in significant mortality, and the surviving mice developed viral persistence and massive immunopathology, including necrosis of the lungs and liver. This suggests that for non-cytopathic viruses like LCMV, hepatitis C virus, and hepatitis B virus, clonal exhaustion may be a protective mechanism preventing severe immunopathology and death.
    Full-text · Article · Dec 2013 · Frontiers in Immunology
  • Source
    • "This reduction in the number of recalled memory cells becomes progressively more severe when the strength of the humoral response is enhanced artificially by elongating the lifetime of circulating Abs (Figure 8). Among the cases where the cellular response alone can successfully contrast the infection are those where heterologous immunity was initially described [3]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The relationship between biological research and mathematical modeling is complex, critical, and vital. In this review, we summarize the results of the collaboration between two laboratories, exploring the interaction between mathematical modeling and wet-lab immunology. During this collaboration several aspects of the immune defence against viral infections were investigated, focusing primarily on the subject of heterologous immunity. In this manuscript, we emphasize the topics where computational simulations were applied in conjunction with experiments, such as immune attrition, the growing and shrinking of cross-reactive T cell repertoires following repeated infections, the short and long-term effects of cross-reactive immunological memory, and the factors influencing the appearance of new clonal specificities. For each topic, we describe how the mathematical model used was adapted to answer specific biological questions, and we discuss the hypotheses that were generated by simulations. Finally, we propose rules for testing hypotheses that emerge from model experimentation in the wet lab, and vice-versa.
    Full-text · Article · Jun 2011 · Autoimmunity
  • [Show abstract] [Hide abstract]
    ABSTRACT: The ability of DCs to induce immune tolerance depends on its maturation status. RelB plays a pivotal role in DCs differentiation. A therapeutic protocol of DCs-based not only induces hyporesponsiveness in T(N)s, but also in alloreactive T(M)s is required. Thus, it is urgent to assess modulatory effects of RelB-silenced DCs on T(M)s and T(N)s. In this study, we constructed lentiviral vector which could efficiently silenced the RelB in DCs (DCs-miR RelB) to keep them immature. These DCs induced antigen-specific hyporesponsiveness in CD4(+) T(N)s. In contrast, upon re-stimulation with mature DCs, CD4(+) T(M)s primed by DCs-miR RelB maintained hyporesponsiveness in terms of proliferation and cytokine production. And these may be associated with micro155 and micro181a expression levels in T(M)s and T(N)s. These results may help developing the DCs-based therapeutical protocols by inducing hyporesponsiveness in CD4(+) T(N)s and T(M)s.
    No preview · Article · Nov 2011 · Cellular Immunology
Show more