What Is An Autoimmune Disease Biology Essay

The map of the immune system is protection of the organic structure from disease infection. Attacking the healthy cells of the organic structure by the immune system is called an autoimmune disease.

Harmonizing to the American Autoimmune Related Diseases Association, the term “ autoimmune disease ” refers to a varied group of more than 80 serious, chronic unwellnesss that involve about every human organ system. In all of these diseases, the underlying job is similar, the organic structure ‘s immune system becomes misdirected, assailing the really organs it was designed to protect. ”

It could be familial and affect many parts of the organic structure. It is more common in adult females than work forces. Initial symptoms may include weariness, musculus aching and low febrility.

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now

Autoimmune diseases are listed as one of the 10 prima causes of decease in adult females up to the age of 65 old ages. ( Rose and Mackay, 2008 )

Diabetess mellitus ( Type 1 )

Diabetes type-1 occurs due to the autoimmune devastation of the beta cells ( insulin bring forthing cells ) taking to no or deficient production of insulin ( hormone modulating blood sugar ) by the pancreas, which causes high blood and urine glucose degrees. This leads to damage in the bosom, eyes, kidney, nervousnesss, gums and dentitions. It by and large occurs in immature kids and unless treated with insulin, it is fatal.

It is a polygenic disease ( several cistrons contribute to its look ) . The IDDM1 cistron located on chromosome 6 is responsible for the histocompatibility upset feature, where the beta cells render improper antigens to the T-cells which lead to the production of anti-bodies that in bend onslaught these beta cells. This could be due to the look of the ‘super antigen ‘ on the beta cells, although the molecular inside informations of this mechanism are non to the full known. ( Atkinson et al, 1990 )

Current intervention includes islet cell organ transplant, wherein islet cells on being injected in the patient ‘s liver begins to bring forth insulin. However it is expensive and besides leads to jobs like ‘hypoglycemia ‘ ( really low blood glucose degree ) .

How many people in the UK have diabetes?

Approximately over 2.6 million people have diabetes in the UK and at that place up to 0.5 million people with diabetes who have the symptoms but are incognizant.

%

[ Beginning: Diabetes UK aa‚¬ ” Core Survey Report ]

0.5 % of the people did non cognize what type of diabetes they had. 48 % of the people are found to hold type-1 diabetes, closely followed by 52 % holding type-2.

The current intervention options are indicated below, with insulin injections being the most popular ( 50 % ) .

[ Beginning: Diabetes UK- Core Survey Report ]

Recombinant-DNA Technology to bring forth Human Insulin

The biosynthetic ‘human ‘ insulin- HUMULIN was one of the first medical specialties to be developed through recombinant DNA engineering and to be approved by the FDA. It was safe, effectual and easy to bring forth. Humulin was foremost developed by Genentech in 1978 utilizing the undermentioned method-

Figure 1- The production of human insulin from bacterial plasmid.

[ Source- hypertext transfer protocol: //scholar.lib.vt.edu/ejournals/JOTS/Summer-Fall-1999/Wiens.html ]

Initiation of insulin secernment in engineered liver cells by azotic oxide [ Muniappan L. and Ozcan S. ]

In the human organic structure, deficiency of insulin leads to chronic hyperglycaemia along with secondary complications such as cardiovascular disease and kidney failure and therefore it is really of import to accomplish sustained and optimum glycemic control. There is a possibility of the development of alternate beta cells as a intervention for diabetes type 1. Normally, the beta cells in the Lengarhans islets produce and secrete insulin merely when the glucose degrees in the blood addition. However it is possible to accomplish insulin secernment from non-beta cells independent of glucose degrees. This scheme involves the production and secernment of insulin by technology the liver cells. The stimulation of insulin secernment is achieved via the azotic oxide tract.

Expression of either human insulin or beta specific written text factors ( PDX I, NeuroD I and Maf A ) in the Hepal-6 cell line or primary liver cells via the adenoviral cistron transportation, consequences in the production and secernment of insulin. The secernment increases treble when these engineered liver cells are treated with L-arginine in the presence of azotic oxide. Stimulation of insulin secernment with the aid of L-arginine from foster beta cells via the production of azotic oxide tract could supply a possible therapy for intervention of type 1 diabetes.

Presently, besides insulin injections, the other option is organ transplant of Lengarhans islets. In cistron therapy, foster beta cells are a possible attack in the intervention for diabetes type 1 to avoid deficiency of insulin production ( Giannoukakis N. et Al ) . For the diabetes Type 1 therapy to be successful, the production and secernment of mature insulin must take topographic point from alternate beta cells in a glucose-regulated mode. An first-class alternate organ to bring forth insulin is the liver wherein successful viral cistron transportation takes topographic point and it expresses GLUT-2 and glucokinase in a mode similar to the pancreatic beta cells ( Chen R. et Al ) . However unlike the pancreatic beta cells, the hepatocytes lack insulin secernment machinery. Insulin look in the liver is achieved by assorted different viral and non-viral vectors ( Li S. et Al, 2001 ) .

The secernment and release of insulin in the pancreatic beta cells is straight influenced by alterations in the blood glucose degrees ( Mulligan RC, 1993 ) . An addition in the blood glucose degrees, besides leads to an change in the map of the beta-cell specific written text factors ( PDX I, NeuroD I and Maf A ) which causes a lessening in the insulin production and hyperglycaemia ( Schepelmann S. et Al, 2006 ) . The production and secernment of insulin in the Hepa1-6 liver cells or the primary liver cells can be achieved through adenoviral cistron transportation that leads to the look of the human insulin or the beta-transcription factors in the liver cells. L-arginine is found to excite the secernment of insulin via the synthesis of azotic oxide in the fibroblasts and cervical carcinoma cells, which would do it utile in the intervention of type-1 diabetes by technology the liver cells.

The incubation of the Hepa1-6 cell lines with an adenovirus showing human insulin led to the production of noticeable sums of insulin as compared to the control virus. On intervention with 1mM or 25 millimeters glucose, the sum of insulin secreted was found to be 60 IA?U/106 cells. The sum of insulin secreted in response to high glucose degrees ( 25mM ) was more or less the same as that secreted at low glucose degrees ( 1mM ) .

Figure 2- Hepa1-6 cells showing human insulin cistron green goods and secrete insulin at 1mM and 25 millimeters glucose concentration.

The intervention of the Hepa1-6 liver cells with 20mM L-arginine for 1 hr in the presence of 1mM glucose increased the secernment of insulin by treble. L-arginine Acts of the Apostless via the azotic oxide ( NO ) pathway and L-NNA is the inhibitor of azotic oxide synthase ( NOS ) independent of L-arginine. The intervention of the Hepa1-6 cells showing the human insulin with 100mM of L-NNA for 1 hr inhibited the secernment of radical insulin. Thus NO is responsible for a part of the basal insulin secernment.

Figure 3- L-arginine stimulates the secernment of insulin in the Hepa 1-6 cells via the azotic oxide tract. Cells were incubated with and without L-arginine in the absence and presence of the azotic oxide inhibitor ( L-NNA ) .

Incubation of the following cell lines- HepG2 ( human liver ) , NIH 3T3 ( mouse fibroblast ) and HeLa ( human cervical carcinoma ) with the human insulin adenovirus led to the production and secernment of insulin. Further incubation with 20mM of L-arginine led to an addition in the secernment of insulin by about 2-fold in the human liver cell line, less than 2-fold in the fibroblast cell line and the human cervical carcinoma. Therefore, the production and secernment of insulin under the consequence of L-arginine is besides possible in non-beta cells and is non merely restricted to merely beta-cells.

Figure 4- L-arginine stimulates the secernment of insulin in assorted cell lines incubated with the human adenovirus insulin cistron. A- Hep G2. B- NIH 3T3. C- HeLa cells.

To look into for the secernment of insulin in the primary rat liver cells, they were cultured and incubated with an adenovirus incorporating human insulin and it was observed that insulin secernment was similar to that of the Hepa1-6 cell lines. Further incubation with 20 millimeters of L-arginine, the secernment increased by more than 3-fold. The secernment of insulin was abolished on intervention with 100 IA?M L-NNA, corroborating that insulin secernment is stimulated by L-arginine via the azotic oxide tract.

Figure 5- Treatment with L-arginine induces the secernment of insulin in primary rat hepatocytes.

Advantages of utilizing E.coli

A assortment of cloning vectors can be employed with it.

The cistron look is easy to command.

The procedure of production is easy and inexpensive.

It yields big sums of recombinant proteins.

Restrictions of utilizing E.coli

It does non execute all the post-translational alterations ( eg-glycosylation ) .

Inclusion organic structures may present as a job.

Secretion is hapless.

If a big sum of insulin is rendered, it may take to complications like hypoglycaemia.

The wall may incorporate constituents that are toxic.

Plasmid instability.

Decision

The above information indicates that the technology of the liver cells and the non-beta cells leads to the production and secernment of insulin. The insulin secernment from these engineered cells is non really antiphonal towards changes in the degrees of glucose, but the secernment additions by up to 3-fold when L-arginine is added through the azotic oxide tract.

The stimulation of insulin secernment from the alternate beta cells through the production of azotic oxide would give a possible therapy to handle diabetes mellitus type-1. Hypoglycemia could be avoided owing to the unstable nature of azotic oxide which leads to a transeunt insulin secernment. Besides this therapy could replace the insulin interventions of diabetes, by farther research on the molecular footing of exciting insulin secernment by L-arginine in the foster beta-cells. It could besides rectify hyperglycaemia in diabetic animate beings showing insulin in liver.