Intestine immune response

Of the 14 volunteers for the Phase I study, 11 were given the transgenic potatoes containing the toxin as vaccine and three had ordinary potatoes. Blood and stool samples were collected from the volunteers to evaluate the vaccine s ability to stimulate both systemic and intestinal immune responses. Ten of the 11 volunteers who ingested the transgenic potatoes had fourfold rises in serum antibodies at some point after immunization, and six of the 11 developed fourfold rises in intestinal antibodies. The potatoes were well tolerated and no one experienced serious adverse effects. 

The intestinal immune response, or more appropriately the immunophysiological response, to tapeworms can be considered in two categories (i) creation of an inhospitable environment and (ii) active humoral events aimed at destruction of the tegument, destro-bilization and scolex detachment. We provide a brief overview of the response to cestodes, with pertinent species-specific and life-cycle stage-specific events given in the following section. 

Mazzarella G, Maglio M, Paparo F, Nardone G, Stefanile R, Greco L, et al. An immunodominant DQ8 restricted gliadin peptide activates small intestinal immune response in in vitro cultured mucosa from HLA-DQ8 positive but not HLA-DQ8 negative coeliac patients. Gut 2003 52 57-62. 

Guiding M, Nordstrom I, Kilander A, et al. (1991) Intestinal immune responses in humans. Oral cholera vaccination induces strong intestinal antibody responses and interferon-y production and evokes local immunological memory. In J. Clin. Invest. 88 143-148. 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

In addition to the wasting of muscle tissue, loss of intestinal mucosa, and impaired immune responses seen in marasmus, children with kwashiorkor show a number of characteristic feamres. The defining characteristic is edema, associated with a decreased concentration of plasma proteins. In addition, there is enlargement of... 

The role of an immune response to intestinal bacteria in the development of UC may not be as strong a contributing factor as it is in CD. The potential role of environmental factors in the development of UC implies that the immune response is directed against an unknown antigen. The findings that development and severity of UC are reduced in patients who smoke, or in those with appendectomies, may support the theory that these factors may somehow modify either the genetic component or phenotypic response to immunologic stimuli.11,13... 

The first inactivated poliovirus vaccine was introduced in the 1950s in an injectable formulation, and replaced in the 1960s by a live oral poliovirus vaccine. The oral poliovirus vaccine not only elicits systemic immunogenicity but also a localized immune response in the intestinal tract. Unfortunately, the oral poliovirus vaccine has the risk of vaccine-associated paralytic poliomyelitis occurring in approximately 1 case of every 2.4 million doses distributed. The risk with the first dose of oral poliovirus vaccine is 1 case in 750,000 doses.11... 

The first rotavirus vaccine was a tetravalent rhesus rotavirus strain. It was licensed in the United States in 1998 and subsequently withdrawn from the market due to an association with intussusception. A pentavalent human-bovine reassortant rotavirus vaccine was approved by the FDA in February 2006. The exact mechanism by which the vaccine produces an immune response is unknown however, this live virus vaccine replicates in the small intestines and induces immunity. 

Although most drugs are absorbed from the intestine by the blood capillary network in the villi, they can also be taken up by the lymphatic system (an integral and necessary part of the vascular system, the function of which is to collect extra tissue fluid and return it to the vascular compartment), particularly by M cells that reside in the Peyer s patch regions of the intestine. Peyer s patches have also been implicated in the regulation of the secretory immune response. Wachsmann et al. [277] reported that an antigenic material encapsulated within a liposome, when administered perorally, is taken up by these M cells and exhibited better saliva and serum IgA (primary and secondary)... 

Finkelman, F.D., Madden, K.B., Cheever, A.W., Katona, I.M., Morris, S.C., Gately, M.K., Hubbard, B.R., Cause, W.C. and Urban, J.F. (1994) Effects of IU12 on immune responses and host protection in mice infected with intestinal nematode parasites. Journal of Experimental Medicine 179, 1563-1572. 

Palmer, J.M. and Castro, G.A. (1986) Anamnestic stimulus-specific myoelectric responses associated with intestinal immunity in the rat. American Journal of Physiology 250, G266-G273. 

Soltys, J., Goyal, P.K. and Wakelin, D. (1999) Cellular immune responses in mice infected with the intestinal nematode Trichuris muris. Experimental Parasitology 92, 40-47. 

The morbidity and mortality that are often associated with human GI helminth infections reflect in part the nutritional consequences of diarrhoea and malabsorption, and the resulting malnutrition that can accentuate the effects of infection by suppressing the protective immune response as well as compromising intestinal repair (Ferguson et al., 1980 Keymer and Tarlton, 1991 Cooper et al, 1992). In experimental rodents the pathology associated with infection is characterized by villus atrophy, crypt hyperplasia, goblet cell hyperplasia and infiltration of the mucosa by a variety of... 

The main site of the mucosal immune system in the gut is referred to as gut-associated lymphoid tissue (GALT), which can be divided into inductive and effector sites. In the small intestine, the inductive sites are in the Peyer s patches, which consist of large lymphoid follicles in the terminal small intestine. The contact with external antibodies triggers a series of cascade events in the body based on immune response (Brandtzaeg et al., 1999). 

Macpherson A.J., Geuking M.B. and McCoy K.D. (2005). Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria . Immunology, 115, 153-163. 

The leading hypothesis for the development of chronic intestinal inflammation is that an abnormal immune response to normal flora might be crucial. This loss of tolerance might be due to a lack of regulatory mediators or cells, or a breakdown in barrier function which makes possible the access of inflammatory bacterial products to the local immune system, thereby overwhelming the normal regulation [3], These possibilities were supported by... 

Therefore, the unresolved question remains of whether chronic, recurring inflammation is the result of a persistent infection with a specific pathogen, an exaggerated exposure to resident normal luminal bacteria products because of increased intestinal permeability or alteration of mucus composition, or an abnormally aggressive immune response to luminal components. 

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