The Evolution and Mechanism of Immunological Memory and Its Impact on Immunology Research.

The Evolution and Mechanism of Immunological Memory and its Impact on Immunology Research. Recently, the Center for Disease and Control reported that it has larned a highly bug, a bacterium, that has the cap superpower of resisting almost any antibiotic k at presentn to human. In addition to resisting antibiotics, these superbugs be deadly. Not only do the bugs ca spend finis to half of the patients with serious infectious diseases, but they besides spread their genes that give wind the bugs foul to other bacteria cellular telephoneular phones ( ground forces TODAY, 2013). This class of superbugs is known as carbapenem-resistant family Enterobacteriaceae (CRE).Currently, CRE argon found mainly in hospitals and nursing homes. However, if these bacteria turning away into the environment, the results fag be devastating. For instance, the bacteria may cause small diseases, much(prenominal) as the car park cold, to become un hold dear sufficient because the CRE alters the small disease contract up to(p)s in a way where it is resistant to vaccination and other medicines (USA TODAY, 2013). Although this shell of bacteria is cutting and deadly, it is non the world-class time that the world has encountered just aboutthing similar to CRE. For instance, staphylococci aureus is one of the well-known examples of bacteria that ar resistant to antibiotics.One reason doctors use antibiotics is because bacteria argon often resistant to the insubordinate governing consistence of a eubstance. The resistance of bacteria to the resistive form is due to natural plectron and genetic mutation. Because bacteria vomit at a rapid rate, some bacteria that contain the adjustive, resistant traits survive and re spend a penny subject that contains the resistant genes. They produce insubordinate-resistant genes with with(predicate) genetic mutation. The alteration made by the genetic mutation support frame a trait that is resistant to the resistant pl acement.As a result, the genetically mutated bacteria pass on be suitable to reproduce without interference from the hosts defense corpse. As a all-powerful tool that the body uses to protect itself from pathogens and bacteria, the repellent formation consist of some(prenominal) parts, and the immunological retentivity is one of the most significant. intellect the ontogeny and the weapon of both the resistive system and immunological memory, new research areas can be developed and new vaccines can be created that target the tolerant systems of pathogens or that alter the repellent system to make it to a greater extent efficient in combating pathogens.Evolution of the ingrained tolerant system and the immanent memory Organisms of the identical species inbred memory are almost the comparable. This memory comes from millions of old age of exploitation (Sompayrac, 2008). The immunological internal memory is based on pattern knowledge receptors. Pattern recogni tion receptors are the main components that allow the innate tolerant system to recognize the pathogens and activate antigens (Kurtz, 2004). These receptors subscribe to gone through millions of years of evolution. One of the main receptors is the monetary value-like receptors (TLRs) (Sompayrac, 2008).Instead of studying the bodys defense to pathogens, watercourse research investigate the evolution of the innate insubordinate system through observing the examples of specific receptors in simple organisms. Wu and Huan (2011) are studying the Toll/interleukin-1 receptor (TIR) and the leucine-rich repeat (LRR), which are the two humankinds that make up the TLR. TIR and LRR are connected by a transmembrane helical starch that is 20 amino group acids long. TIR plays an authorized mathematical function in activating the innate resistive system by detecting lipopolysaccharide from gram-negative bacteria.The interaction amid the receptors of both the innate immune system and bact eria is handled by LRR. body- prepare 1 congresswoman of evolutionary tree of invertebrates. Amphimedon came before Cnidarians. (Wu and Huan 2011) To understand the evolution of TLR, scientists have to discover when the TIR and LRP first appeared. One research conducted by Dr. Wu and coworkers (2011) attempted to create a phylogenetic tree of the TLR. After comparing the protein of contrary organisms, they discovered that sponges, much(prenominal) as Amphimedon queenslandica, contained a single TIR domain that was distinctly link to the TLR of vertebrates (Wu and Huan, 2011).The decision prompted them to conduct further analyses of TIR proteins in organisms that appeared later than Amphimedon queenslandica. As shown in Figure 1, cnidarians appeared afterward Amphimedon queenslandic. Cnidarians had TIR proteins that were similar to that of vertebrates. Cnidarians are one of the simplest organisms, and their TIR proteins allow them to have the symptomatics of allorecongnition, the ability to distinguish its own tissue from some other (Wu and Huan, 2011). LRR was not found in cnidarians.The conclusion of TIRs that were similar to vertebrates in cnidarians only answered part of the question. Wu and Huan were not able to find the first appearance of LRR. They found the combination of LRR and TIR to make TLR after analyzing the TLR proteins of three basal deuterostome invertebrates and five protostome mammals. The conclusion is that the combination of TIR and LRR occurred after the leaving of bilateria and nonbilateria. After the separation, the receptors became to a greater extent obscure because they started to have the capability of allorecongnition and a sidesplitting mechanism (Wu and Huan, 2011).After further comparison of the TLR of vertebrates, they determined that another combination occurred between the TIR and LRR during the evolution of primates (Wu and Huan, 2011). They believe that this second combination gave rise to our amaze TLR, which has the capability of signaling the innate and alerting the adaptative immune system. The innate immune system is the oldest defense system. Because of this, the earliest form of the innate immune system of simple organisms, such as cnidarians, are closely related to vertebrates, such as mess.As organisms moved from water to land, they encountered to a greater extent types of pathogens. Pressure from pathogens caused umpteen organisms to develop an innate memory that is more expansive. However, as organisms became more complex, the innate memory did not adequately protect the organism. The inadequacy of the innate immune system windings to the fundamental law of the accommodative immune system. Evolution of the adjustive immune system and the adjustive memory The adaptive memory is different from the innate memory because the receptors in the adaptive memory begin life with a blank memory.There are two major types of lymphocyte receptors that play an weighty role in the ada ptive memory B cell and T cell. It is hypothesized that B cell receptors (BCRs) and T cell receptors (TCRs) have a common ancestor (Flanjnik et al. 2010). The characteristics of these genes are discovered in gnathostomes, but not in agnatha. These characteristics include world able to have large come in of cells for differentiation. This finding caused scientists to create a theory called the big bang theory of adaptive immune system (AIS) emergence.The finding also prompted scientists to examine the varys of these receptors characteristics from gnathostomes to mammals. These finding lead scientists to determine the origin and evolution of the adaptive immune system. Figure 2 A summary of the immunoglobulins structures and forms found in gnathostomes to mammals. The first receptor that researchers focused on was the B cell receptors. Immunoglobulin M (immunoglobulin M) is a B cell receptor that has the same function in all organisms starting from the gnathostomes (Flajnik and Ha sahara, 2009). Some of these functions include having its transmembrane form defining the B cells.In humans, IgM is responsible for increase the complement activation during the interaction of antigens and lymphocytes. This characteristic caused the IgM to be very efficient at causing lysis in microorganisms. IgM also causes clumping of pathogens. The clumping of pathogens was discovered in haggard look for, while the increasing of the complement activation was found in cartilaginous fish. This showed that although the function of IgM did not change, it was altered as organisms became more complex. Immunoglobulin D (immunoglobulin D) is another B cell receptor.IgD is different from IgM because although both humans and bony fish have IgD, IgD in humans is attached to the open air of basophils, while in bony fish, the IgD is attached to granulocytes surface (Flajnik and Hasahara, 2009). Although the function of IgD is still unknown, the finding of IgD at two different locations ind icates that in that respect are possible changes in its functionality. The only vertebrates that do not have IgD are birds. These findings support the idea that like IgM, IgD is an old antibody class that has changed its function from gnathostomes to mammals. Amphibians have a B cell receptor known as IgY.Mammals have immunoglobulin G, IgE, and IgA B cell receptors. Mammals obtained IgG and IgE through the alternative splicing of IgY. IgG has the same function as IgY. IgEs function is different from IgG because it is responsible for releasing various p ill-treatacological mediators, while IgGs function is to activate complement when reacting with an antigen. IgA is found in reptiles. The denudation of IgE, IgG, and IgA in mammals reinforces the idea that as organisms became more complex the type of immunoglobulin receptors increased, thus making the adaptive immune system more complex. Like BCRs, some TCRs had a similar situation. ? T cell receptors from jawed fish to mammals have the same function. ? T cell receptors in both sharks and marsupials are structurally the same. Both sharks and marsupials have three domain receptor set up with two amino-terminal V domains and a membrane-proximal C domain. However, the formation of the V domains and C domains are different for sharks and marsupials. The V domain for sharks is made from VDJ rearrangement, while the V domain for marsupials is generated by one set of V, D and J segments of a pre-rearranged VDJ gene. The function of these receptors has not been reported.The difference in the formation of the V domain indicates that due to pressure from the environment, part of the adaptive immune system underwent evolution to meet the needs of marsupials. Examining the change of the receptors from the gnathostomes to mammals has shown that the adaptive immune system underwent change as organisms became more complex. However, this does not illustrate how the adaptive immune system formed. The recombination-activating gene (RAG) transposon and the hale-genome duplication are the two events that brought about the adaptive immune system (Flajnik and Hasahara, 2009).RAG encodes enzymes that impact the rearrangement of T cell receptors and immunoglobulin. There are two main types of RAG in vertebrate immune system RAG-1 and RAG-2. These two types of RAGs play a major role in the formation of immunoglobulin superfamily (IgSF). During the 1970s, two Japanese researchers discovered that recombination signal sequences (RSSs) were flanked by V,D, and J rearranging segments. These segments within the RSSs had repeats that were reminiscent of a transposon. From this, they reasoned that a transposon invaded IgSF (Flajnik and Hasahara, 2009).The infringement resulted in IgSF not being able to function unless through recombinase. Flajnik and Hasahara believed that IgSF genes were invaded by the RAG transposons. Researchers could not obtain all RAG genes from agnatha, but they were able to obtain it from gnat hostomes. This indicates that the RAG transposon plays a role in triggering IgSF (Flajnik and Hasahara, 2009). The usurpation of the genome by the transposon was vital for the adaptive immunity system because it gave rise to BCR and TCR, which are part of the IgSF and both play a major role in the adaptive immune system.The occurrence of whole genome duplication also plays a role in the formation of the vertebrate adaptive immune system. Susumu Ohrno was the first researcher to propose the idea that the vertebrate genome underwent two rounds of whole gene duplication (WGD), which occurred after the emergence of the jawed vertebrates. WGD is an event that creates an organism with additional copies of the entire genome. At first, this idea was met with great skepticism but scientists now accept the idea because many ohnologues are essential components of the jawed ertebrate adaptive immune system. Ohnologues are paralogues that are close to the origin of vertebrates through whole-ge nome duplication (Flajnik and Hasahara, 2009). Understanding what influences the evolution of the adaptive memory is also important in correspondence the evolution of the adaptive memory. There are many speculations on why the adaptive immune system is developed. Some reasoned that because the innate immune system was inefficient and difficult to regulate, it lead to the development of the adaptive immune system.Pressure from pathogens and the ability to have few offspring also caused natural extract to favor the formation of an adaptive immune system (Flajnik and Hasahara, 2009). For instance, organisms such as seahorses live in an environment that has few pathogens that will threaten its livelihood. In addition, seahorses produce large amount of offspring. Because there are not many pathogens that a seahorse encounters, the innate immune system is adequate in dealing with the few pathogens. Organisms such as sharks are predators, and many produce few offspring during their lifet ime.This pressurizes sharks to have an adaptive immune system because the offspring will have the ability to combat pathogens of all types. Sharks adaptive immune system is not as complex as vertebrates that dwell on land because water does not contain as many pathogens as compared to land. Mazmamian of California Institute of Technology recently conducted a research that indicated that microbiota had a larger influence on the evolution of the adaptive immune system than pathogens influence (Lee et al. , 2012). Microbiota have a symbiotic relationship with the body.An example of this occurs with bacteria located in the gut. A function of these bacteria is that they help fodder move quickly through the body. Researchers have discovered that the microbiota, which includes bacteria and viruses, have many different antigens. This provides the adaptive immune system and the microbiota with a gainsay because the immune system must(prenominal) either react toward or sheer the foreign a ntigen (Lee et al. , 2012). In recite to anticipate overreaction from both parties, both the adaptive immune system and the microbiota develop tolerance through the expansion of regulative T cell (Lee et al. , 2012).Scientists speculated that this symbiotic relationship between vertebrates and microbiota could have influenced the adaptive memory because symbiotic microbiota could have pressured vertebrates to develop the current adaptive immune system that have developed tolerance to bacteria that is good for the body (Lee et al. , 2012). Current research applications Edward Jenner was the first to start experimenting with vaccines. Afterwards, research on vaccines became more complex. vaccine researches now include the study of the pathogens and virus immune system. mycobacteria atomic number 65 and human immunodeficiency virus.One of the most studied pathogens is the Mycobacterium tuberculosis. Currently, there are two standard strategies to combat Mycobacterium tuberculosis. The first system involves identifying the protein that is produced by the bacterium that is essential to its virulence (Flynn, 2004). Once the protein is identified, the immune system can neutralize the protein. This will result in the bacteria not being infectious to the body. This strategy cannot be applied to Mycobacterium tuberculosis because although there is ongoing research, scientists have not been able to identify the protein that causes its virulence (Flynn, 2004).Mycobacterium tuberculosis main virulence is its ability to survive within macrophages. The second strategy is to use an attenuated form of the pathogen, which will cause an effective immune response, but will not cause disease. The second strategy involves the adaptive memory immune system because the vaccine is causing the adaptive memory to remember the pathogens that is similar to Mycobacterium tuberculosis. Currently, the second strategy is implemented through the vaccine Bacillus Calmette-Guerin (BCG) (Fly nn, 2004). BCG is used by 4 million people around the world (Flynn, 2004).Although BCG is the most commonly used vaccine to treat tuberculosis, it is still not effective because the vaccine can only prevent tuberculosis only in children, but not in adults. Researchers are now investigating the immune response to M. tuberculosis in order to create more effective vaccines. Current research involves injecting patients with the cytokine interleukin 12 (IL-12) (Flynn, 2004). Il-12 plays an important role in visualizeling M. tuberculosis infection. Studies have shown that when mice are injected with the Il-12 DNA, the amount of bacterial numbers of M. tuberculosis is greatly reduced.Tumor necrosis factors ? (TNF-? ) and interferon-gamma (IFN-? ) are important cytokines that play an important role in combating M. tuberculosis. IFN-? is a central cytokine in control of M. tuberculosis because it activates the macrophages to attack M. tuberculosis (Flynn, 2004). Organisms with defective IFN -? are more susceptible to infections. TNF-? is important because in synergy with INF-? , it leads to the formation of nitrogen oxide synthase 2 (NOS2) (Flynn, 2004). Although NOS2s role is not clearly known, it is shown that when organisms were under the infection of M. uberculosis, NOS2 verbal expression was low (Flynn, 2004). This indicates that a high expression of TNF-? , IFN-? , and NOS2 can cause the body to fend off tuberculosis. It is known that overexpression of TNF-? can also cause harm to the body by increasing the chance of getting tuberculosis (Flynn, 2004). As a result, researchers are now conducting vaccine research on how to create the right amount of expression of the three cytokines that allow the immune system to effectively combat M. tuberculosis. The human immunodeficiency virus (HIV) is another area targeted for vaccine research.Currently, there are three vaccines come alonges in creating a vaccine that targets the HIV-1 protease (McMichael et al. , 2009). HIV protease is an important aspect of the HIV life cycle. any of these methods have failed. Scientists are now proposing to use less empirical approach and to focus more on understanding the immune response to HIV-1 infections when producing new vaccines (McMichael et al. , 2009). During an HIV infection, natural killer cells (NK) become activated. NK cells have the ability to control HIV replication through cytolysis of the infected cells.NK cells also have the electrical condenser to influence T cell responses (McMichael et al. , 2009). HIV-1 has responded by reducing its receptors, making it harder for the NK cells to detect the infected cells. Current research is focused on priming the antiviral activity of the NK cells through vaccination. Researchers are cautious when activating the innate immune system because the innate immune response can be hurtful because the activation of the innate immune system produces pro-inflammatory cytokines and chemokines, which can publicis e the HIV-1 replication (McMichael et al. , 2009).As a result, the vaccine-induced activation of the innate immune system must be thoroughly tested and used with caution. Conclusion There are many laboratories around the world conducting research on creating an effective vaccine to target the different diseases that people combat every day. Although this strategy is new, implementing a research strategy that focuses more on the immune system when creating vaccines will allow the vaccine to be more effective. In addition, implementing this strategy requires indistinct understanding of the mechanism and evolution of both the innate and adaptive immune systems.Both the innate and adaptive immune system evolve from being able to perform simple tasks in primitive organisms to perform complex tasks in complex organisms, such as humans. Therefore, in order to create a vaccine, it is vital to start from simple organisms. Once that is accomplished, one can build on top of the newly develope d vaccine that targets more complex organisms and combat the superbug carbapenem-resistant enterobacteriaceae. Literature Cited 1. Flajnik and Hasahara, Martin F. , and Masanori Kasahara. Origin and Evolution of the Adaptive tolerant form Genetic Events and Selective Pressures. Nature Reviews Genetics 11. 1 (2009) 47-59. Print. 2. Flynn, JoAnne L. Immunology of terabit and Implications in Vaccine Development. Tuberculosis 84. 1-2 (2004) 93-101. Print 3. Kurtz, Joachim. Memory in the infixed and Adaptive Immune Systems. Microbes and Infection 6. 15 (2004) 1410-417. Print 4. Lee, Yun Kyung, and Sarkis K. Mazmanian. Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System? Science 330 (2012) 1768-773. Print. Kurtz, Joachim. 5. McMichael, Andrew J. , Persephone Borrow, Georgia D.Tomaras, Nilu Goonetilleke, and Barton F. Haynes. The Immune Response during Acute HIV-1 Infection Clues for Vaccine Development. Nature Reviews Immunology 10. 1 (2009) 11 -23. Print. 6. Sompayrac, Lauren. How the Immune System Works. Malden, MA Blackwell Pub. , 2008. Print 7. USA TODAY. CDC Sounds Alarm on Deadly, Untreatable Superbugs. USA TODAY. N. p. , 5 Mar. 2013. Web. 23 Mar. 2013. 8. Wu, Baojun, and Tianxiao Huan. Domain confederacy of the Vertebrate-like TLR Gene Family Implications for Their Origin and Evolution. Journal of Genetics 90. 3 (2011) 401-08. Print