Immunology Toll Like Receptors Term Paper

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Immunology - Toll-Like receptors

The family of Toll-like Receptors has gained in importance since the discovery that they could be potential regulators and controllers of the immune response system in the human body as they are capable of recognizing the molecular patterns that are associated with pathogens. It was found that Toll-like Receptors are capable of recognizing endogenous ligands, as well as microbial components and those Toll-like receptors are activated by small-molecular-mass synthetic compounds and for these reasons the Toll-like Receptors are significant in that they are potential targets for the development of new therapies for several diseases. (Toll-like receptors as potential therapeutic targets for multiple diseases)

Toll Receptors were first found in an insect, the fruit fly Drosophila and these receptors were found to play a significant part in the innate immunity by the recognization of microbial particles and also by triggering the immune cells against the source of the pathogenic microbial particles. Homologies of the Drosophila Toll Receptors were the found in the mammalian immune cells and these receptors were named Toll-like Receptors. It was found that the Toll-like Receptors were similar in function in microbial recognition and activation of the innate immune system against the microbial sources. Ten types of Toll-like Receptors have been identified till now and are called TLR's one to ten. (Toll-Like Receptors)

The type I trans-membranous proteins called Toll Receptors has significant roles in the development and immunity of mammals. When the genomes of the mouse and human were compared against the Drosophila fruit fly and the anopheles mosquito, it was found that though they possess the same number of ten Toll Receptors the phylogenic analysis indicated that the families of Toll Receptors expanded independent of each other in insects and mammals. Distinctions have also been seen in the activation and signaling between Tolls in insects and Toll-like Receptors in mammals. It appears that the Toll-like Receptors in mammals are solely dedicated to the defense of the host body the Toll receptors in insects are predominantly linked to other functions, which could be development. (Biology of Toll receptors: lessons from insects and mammals) Toll-like Receptors in mammals have been found to detect specific components on bacterial and fungal microbial pathogens and most recently in the recognition of viral attacks too. Signaling pathways are seen via the Toll-like receptors and originate from the conserved Toll/IL receptor domain. It has also been found that the Toll-like Receptors have their own signaling system that is characteristic of their specific functions. (Toll receptors and pathogen resistance)

The defense tactics employed by host bodies against pathogenic microbes in mammals are centered on two types of immunities, one called innate and the other called adaptive or acquired immunity. Adaptive immunity is seen only in vertebrates and is a highly sophisticated system to combat pathogenic micro-organisms. It takes several moves before they come into play effectively and in the process consumes precious time that cannot be lost in tackling the marauding pathogens. Hence the host body needs to combat the pathogens before the adaptive immune system can take over fully. In invertebrates the innate immunity system is seen to provide efficient host defense as they do not have any adaptive immune system. Innate immunity is phylogenetically preserved and is seen in all multi-cellular organisms including humans. (Micro review: Toll receptors and pathogen resistance)

It has the capability to detect pathogenic microbial invasion and pose a first line of host defense. It has become evident that Toll-receptors in insects and Toll-like receptors in mammals play a significant role both in the detection and in the signaling using the pathways. It is these recent findings that have shown the importance of Toll-like Receptors and revolutionalized our concept of how the innate immune system works. These include the capacity of the Toll-like Receptors to identify microbial pathogens like fungi, bacteria and even viruses too. The discovery of the Toll-like Receptor has made us come to know that the innate immune system is an adept system that can sense the invasion of microbial pathogens. (Microreview: Toll receptors and pathogen resistance)

The innate immunity system is considered as the antigen-nonspecific defense mechanisms that seen to be used by the host body instantaneously or within a short period of time after exposure to a pathogenic microbe. This immunity is inherent in multi-cellular organisms including humans and is the initial reaction of the body to destroy the microbes and prevent infection. Innate immunity does not possess the capability to recognize all possible microbes and instead has been so designed to recognize a few highly conserved structures that exist in many microbes. These structures are known as pathogen-associated molecular patterns. These could be LPS from the gram-negative cell wall, peptidoglycan and lipotechoic acids from the gram-positive cell wall. The sugar mannose and bacterial DNA found in bacterial proteins, the double stranded RNA from viruses and glucans from the fungal cell walls. This pattern recognizing receptors are found in the body of the host and it is here that the importance of Toll-like receptors in the innate immune system and the quick response to the invasion of such microbes.

Totally it is believed that the innate immune system is capable of recognizing almost one thousand of such microbial molecular patterns. The innate immune system response includes the phagocytic cells, cells that release inflammatory mediators like basophils and mast cells, natural killer cells and molecules such as complement proteins, acute phase proteins and cytokines. (The Innate Immune System) A proper understanding of the important roll of Toll-like receptors in the innate immune system and the innate immune system could give ways to increase the efficacy of the innate response systems to infection. This then could reduce the overdependence on antibiotics and other drugs in the treatment of bacterial infections. This research would also provide added insights to bio-defense studies. Many potential bio-agents that could be used by terrorists are microbes that could intervene at the innate immune response stage and produce a marked early challenge to the host defense system. Studies of the innate immune system may help in neutralizing such a threat. (Multidisciplinary UI Team Awarded Grant to Study Innate Immune System)

In today's world it is becoming even more and more important to manipulate the innate immune system to give better medical care world wide. Scientist in the field of immunology have been throwing in efforts on the better understanding of the working of the Toll-like receptors in the innate immune system to provide practical and effective solutions to the health problems seen globally. These include possible treatments for cancer and infectious diseases. Some important steps forward have been achieved and this can be seen in the near future possibility of using immuno-therapy in the case of many tumors. Early solutions if found in the field of infectious diseases would prove very useful in E-coli infections, HIV infections and West Nile viral infections. (Immunology)

Severe sepsis is another area of concern and studies in the innate immune system are expected to produce some solutions here. Besides antibiotic therapy there is no other solution currently available. Still many patients are lost due to over activation of the host inflammatory system and the consequent coagulapathy and deregulation of the normal vaso-active tone. Knowledge that the critical part of the host response happens at innate defense level is there, without the requirement for antigen processing or clonal expansion of cells to work against the invading pathogens. The new discoveries on Toll-like Receptors in the innate immune system could provide an answer to this. (Toll-like receptors: the key to the stable door?)

Another area where results are expected in the near future in the study of Toll-like Receptors and the innate immune system is in the treatment of Asthma. Asthma is a chronic disease caused by inflammation in the air passages caused…

Sources Used in Document:


Cohen J; Hopkins P. (April 6, 2002) "Toll-like receptors: the key to the stable door?" Retrieved from db=PubMed& list_uids=11983029& dopt=Abstract Accessed on 12/20/2004

Imler, Jean-Luc; Zheng Liangbiao. "Biology of Toll receptors: lessons from insects and mammals" Retrieved from Accessed on 12/20/2004

Lin-fu Zhou; Kai-sheng Yin "Toll-like receptors: function and roles in asthma." Retrieved from Accessed on 12/20/2004

"Multidisciplinary UI Team Awarded Grant to Study Innate Immune System" (November 24, 2003) Retrieved from Accessed on 12/20/2004

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