Themis Genetic Summary

Crohn’s disease (CD) is a systemic auto-immune disease that is marked by abnormal inflammation of the gastrointestinal (GI) tract, it affects any part of the GI tract from mouth to anus. CD mainly presents in three areas: the small intestine, the colon, and the perianal region. CD mostly occurs between the ages of 15 and 30 years, or between the ages of 60 and 80 years of age. The exact etiology of Crohn’s disease is unknown. As stated by Mazal (2014) “Genetic predisposition—especially familial aggregation—seems to be the strongest independent indicator of which individuals will develop Crohn disease” (p.298). An increase diet in milk protein, milk protein and polysturated fatty acids is also a possible factor in disease incidences. Smoking may also double the risk of developing CD.

This review will explain Crohn’s disease and Ulcerative colitis, two types of inflammatory bowel disease that affect millions of people. These diseases are chronic that affects certain parts of the intestine gastrointestinal tract. People who has this disease are troubled with a variety of side effects that they will have to live with for the rest of their lives. To this day, there are no medical cure for these diseases, however there are several treatment options that are helpful. These diseases are still being studied for researchers to fully understand the causes, possible preventions, and cure for IBDs. Countless researches and studies are still under development, there have been many discoveries thus far, but nothing concrete.

The patient was presented to me with diagnosed crohn’s disease, in remission stage. Crohn’s disease is a chronic inflammatory disease of the intestines. Primarily, it causes ulcerations in the small and large intestines but has been seen to affect the digestive system anywhere from the oral cavity to the anus. The disease has no known cure but once the disease begins it proceeds to vary between periods of inactivity (remission) and activity (relapse). The cause of crohn’s disease is unknown but from research it is suspected that infections by certain bacterium could contribute to the disease. The activation of the immune system in the intestines is seen to be of importance to patients with crohn’s. The immune system causes inflammation within the tissues where it occurs. In normal cases the activation occurs when the body is exposed to harmful invaders. With patients with crohn’s disease the immune system is abnormally activated in the absence of any invader, thus resulting in chronic inflammation and ulceration as seen in the figure below. The disease causes abscesses and a cobble stone appearance to the infected area in the body, this infection causes the immune system to activate in an inflammatory response.

IBD is the result of an abnormal innate repsonce to antigens in the intestinal flora, thus activating the adaptive immune repsinse; a process in which genome wide stidues have implicated several genes such as NOD2 and ATG16L1, both involved in the intracellular processing of bacterial antigens. PSC has shown similar mechanisms characterized by Th1 cytokines and structuring. However, PSC has aslo shown close association with classic autoimmune diseases such as type 1 diabetes, rheumatoid arthiritis, and others; has shown a strong association with the human leukocyte antigen(HLA) DRB1*0301 haplotype; and has shown a variety of autoantigens to neutrophils and biliary epithelial cells (BEC). (1) Thus suggesting the immunopathogenesis of PSC is complicated and may have more than one cause.

Crohn’s disease is an inflammatory condition that is immunologically mediated. Even though the etiology of the disease is not yet determined, results from different researches such as human genetics, clinical tests and basic science have given significant insights in the inflammatory disease pathogenesis. In addition, the studies reports that Crohn’s disease is heterogeneous disease that is characterized by different genetic abnormalities that results to T cells responses. The research paper has highlighted various signs of the disease that indicates that T cells usually response to the environment. For instance, the paper states that T cells are important to an individual’s immunity and has both protective and harmful immune response. The research paper has a purpose statement that provides the theme or the question that is being examined in the paper. The paper also reviews both the Crohn’s mechanism and the assumed pathophysiological mechanisms. Assumed pathophysiological mechanisms include intestinal permeability, infectious agents, pro-inflammatory moles and the abnormal immunological response. On the other hand, signs and symptoms of the Crohn’s disease include diarrhea, weight loss, abdominal pain and fever.

There are currently two tumour necrosis factor alpha (TNFα) antagonist available on the PBS for treatment of IBD: infliximab and adalimumab.1 Another biological is vedolizumab which is a gut specific humanised monoclonal antibody that binds to and inhibits α4β7 integrin expressed on the surface of lymphocytes preventing their binding to mucosal addressin cell adhesion molecule-1 expressed on vascular endothelial cells within the GI tract.16 Blocking this binding prevents lymphocyte migration into intestinal tissue thus reduce inflammation.16 Lastly, the most recent approved biological agent by PBS is

For instance, Crohn’s disease(CD) is a chronic relapsing inflammatory bowel disease (IBDs), which affect the various areas of GI tract (from mouse to anus) and lead to abdominal cramps, weight loss, diarrhea, fever and the other symptom. According to the survey, Crohn’s disease was found to be more common in developed industrialized countries than less developed tropical countries because people who lived in developed areas have less chance of exposure to helminthes. Therefore, although the cause of Crohn’s disease is not fully understood, but it is consider to be related to environmental, genetic factor and autoimmune reaction. Medically speaking, Crohn’s disease is classified as an autoimmune disorder. Usually, there are many harmless and

This essay will focus on Crohn’s disease and pathological changes that may occur in the small intestine as a result of the inflammatory process and discuss the scientific reasons for the possible treatments relating these to pathological processes.

Most of the T cells in the gastric mucosa differentiate into Th1 cytokines, the others become anergic. Anergy of T cells may be brought about by the interaction of T cells with the gastric epithelial cells that express B7-H1. B7-H1 is a costimulatory molecule that increases during H. pylori infection. In gastric epithelial cells the development of Treg cells from naïve T cells is brought about by exposure to H. pylori via induction of BH-71. This suggests that H. pylori might utilise the epithelium to promote the development of Treg cells which play a vital role in suppressing effector T cells. Because of this the existence on Treg cells in H. pylori infection may diminish the adaptive immune

Cytokines, which are released by macrophages in response to various antigenic stimuli, blind to different receptors and produce autocrine, paracrine, and endocrine effects. Cytokines differentiate lymphocytes into different types of T cells. Helper T cells, type 1 (TH-1), are associated principally with CD, whereas TH-2 cells are associated principally with UC. The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process (Lashner,

genetic predisposition, chronic stomach infection, gallstones, chronic pancreatitis, cirrhosis, exposure to chemicals.This vital function also exposes the gut and its organs, the liver and pancreas , to ingested toxins that can initiate cancer and to materials that damage the gut lining, also potentially leading to cancer. Because diet greatly influences the chances for contracting these cancers, it is understandable that stomach cancer is the world’s most common type. Surprisingly, however, cancers of the small bowel are

Analysis of data showed that there was a higher percentage of macrophages than B cells present within the MHC positive population. The remaining population of cells (3%) can be attributed to dendritic cells, which have been previously shown to form a small percentage (3%of cells) within zebrafish gut by Wittamer et al, 2011. While we used visual morphological differences to distinguish between B cells and macrophages, future experiments can make use of the mhc2dab:GFP; cd45:DsRed double-transgenic (Wittamer et al,2011) which would enable us to distinguish between macrophages (mhc+; cd45+) and B cells (mhc+) through fluorescent markers thereby allowing us to FACS sort pure populations if needed as well. We saw that within the mhc+ cells in the wild-type zebrafish gut, phagocytosis by macrophages within gut phagocytes was higher than B cells.This high proportion of phagocytosis by macrophages within leukocyte populations is consistent with Page et al’s, 2013, in-vivo study in which more than half of the phagocytic cells in murine peritoneal cavity were macrophages. We further quantified phagocytic efficiency of each cell type within their respective populations. 54.5% of macrophages within the macrophage population were phagocytic and 33.8% of B cells within the B cell population were phagocytic. Interestingly, previous research by Li et al, indicated that teleost fish can show up to 60% of phagocytic behaviour by B cells. However, in contrast, a study by Page et al, showed only a 2% phagocytic efficiency of zebrafish B cells. While the researchers acknowledge that there is a possibility that intrinsic experimental conditions could have contributed to this result, it should also be noted that the in-vitro experiment used B cells from the kidney to test for phagocytic efficiency. B cells from the gut may have

Celiac disease is an enteropathy mediated by an autoimmune response to gluten, a protein complex found in the endosperm of wheat, barley, and rye.1 The immune response is triggered by both environmental and genetic factors in individuals susceptible to the disease resulting in elevated levels of immunoglobulin A (IgA) antibodies to tissue transglutaminase (tTG), duodenal mucosal villi atrophy, and the inability of tight junctions to properly act as a barrier between the gastrointestinal tract and the systemic portion of the body.1

Schenk, Bouchon, Seibold, and Mueller hypothesized that patients with active irritable bowel diseases have upregulated TREM-1 expression on intestinal macrophages, which could contribute to excessive inflammation and tissue destruction. Through analysis of mice induced with IBD, they found that there was a five-fold increase in frequency of TREM-1 expressing macrophages. Expanding on the idea of TREM-1’s association with pathology, Schenk, et al, explored the extent of TREM-1 expression in relation to the severity of IBD. While IBD remained in remission, TREM-1 mRNA was “nearly undetectable” through PCR, but 3-5 days after inducing the pathology, the mRNA was highly upregulated. This proves that the TREM-1 expression is directly correlated with the increase of inflammatory responses.

Animal Models of IBD: What are the main ones and how are they relevant for IBD?