Molecular Mimicry and Its Effect on Crohn's Disease
Molecular mimicry is a well-documented biological phenomenon and its link to autoimmune diseases has led to extensive research. From an epidemiological perspective, autoimmune diseases have been found to exhibit multifactorial origins. In most cases, genetic predisposition, as well as environmental factors leads to tissue injury owing to the activity of autoreactive antibodies or T cells. One of the most striking characteristics of autoimmune diseases is that the initial biological processes that lead to the loss of tolerance do not match with clinical manifestations. These manifestations occur long after the mechanisms associated with loss of tolerance. It is believed that loss of tolerance is responsible for the severity of chronic autoimmune diseases. Currently, there are several pathological processes involved in the breakdown of immunologic tolerance. These mechanisms include activation of polyclonal lymphocytes, abnormalities in self antigens presentation, molecular mimicry, and presence of autoreative lymphocytes (Bellone, 2005). In Crohn’s disease, as well as other autoimmune diseases such as ulcerative colitis, multiple sclerosis, and type 1 diabetes mellitus, molecular mimicry is hypothesized to be one of the key mechanisms leading to the breakdown of immunological self tolerance. Therefore, this paper will provide a comprehensive overview on molecular mimicry and its effects on autoimmune diseases with a principal focus on Crohn’s disease.
Molecular mimicry is a pathological phenomenon with immense clinical significance. For instance, treatment of autoimmune diseases has been facilitated by the understanding of the ways through which molecular mimicry exists. Foremost, molecular mimicry occurs through T cell selection which involves that activity of major histocompatibility-complex (MHC). Second, molecular mimicry occur through co-stimulation that is triggered by foreign antigens leading to upregulation of antigen presentation. Third, this phenomenon occurs through the recognition of host target antigen by self reactive T cells (Leech, 1998).
In understanding the phenomenon of molecular mimicry, immunologic basis of the process explains how autoimmunity develops. From an immunological perspective, T cells perform their immunological functions including cellular apoptosis, tolerance and productive expansion depending on their recognition by the antigenic proteins. Therefore, T cell antigen receptors play the pivotal role of recognizing foreign antigens such as bacteria and viruses. Despite the flexibility of T cells recognition by T cell antigen receptors on antigen-presenting cells (APCs), these receptors have been found to cross-react with self antigens leading to the development of autoimmunity. Ordinarily, the human body prevents autoimmunity through immunological tolerance. In this process, the body cannot mount immunologic response to self antigens through central and peripheral tolerance. Central tolerance occurs in the primary lymph organs, primarily the thymus in which self reactive T cells are deleted during their maturation. In this clonal deletion process, T lymphocytes that possess receptors for self antigens are destroyed through apoptosis. The T cells that escape central thymic deletion are rendered deleted peripherally or they are not recognized by MHC complex. Therefore, these cells are referred to as ‘ignorant T cells’ and their cognate antigens are called ‘cryptic antigens’ (Acharya et al., 2010).
Central and peripheral tolerances are the two mechanisms that protect individuals against autoimmunity. Therefore, the development of autoimmune diseases such as Crohn’s disease involves the breakdown of tolerance. Clinical research indicates that infections play key roles in stimulating tolerance breakdown through diverse pathological mechanisms. Molecular mimicry is one of these pathophysiological mechanisms that are involved in the breakdown of tolerance. This is reaffirmed by the theory of molecular mimicry that states that autoimmunity develops after an infection, primary when immunological response towards the pathogen, foreign antigen cross-reacts with self antigens in the host’s body (Acharya et al., 2010). This forms the basis for molecular mimicry, a phenomenon associated with the origin of Crohn’s disease.
It is believed that the basis for molecular mimicry is amino acid sequence homology. In most autoimmune diseases, CD4+ T cells have been found to be the main effectors. Therefore, molecular mimicry occurs through an activation of CD4+ T cells by antigenic determinants that are present in the foreign antigen, in this case an infectious agent such as bacteria or virus that exhibit similar homological characteristics. In nature, humans have been found to share numerous amino acid sequences with other organisms, but most of these sequences have not been found to have any significant clinical correlation. In addition, peptide-sequence data indicate that there are up to 10 protein-sequence matches for 5 amino acid sequences available in the peptide-sequence data bases. This implies that molecular mimicry which exhibits some aspects of amino acid sequence homology can occur in most organisms. However, it is worth noting that this phenomenon does not only rely on the peptide-sequence. Instead, it appears there is a complex process involved in molecular mimicry. Some of these processes that explain how T cell antigen receptors identify peptide
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- Patrick Kimuyu (Author), 2018, Molecular Mimicry and Its Effect on Crohn's Disease, Munich, GRIN Verlag, https://www.grin.com/document/388522