'Evolution of the Immune System\r'

'John Frelinger Dr. Travis Organic Evolution 30 April 2012 Evolution of the repellent ashes Animals ar forever and a day bombarded by an longly varied stray of affection causing pathogens including bacteria, fungi, computer viruses and other parasites. The number of microbes living in the gentleman trunk show upnumber the actual human cells by a factor of 10, and for e real atomic number 53 species of animal and plant on Earth, there are viruses that infect them. With the unrelenting threat of disease-causing pathogens all somewhat us, and eventide within us, how substructure the eer penetrable organisms defend themselves?Evolution has provided an answer to this problemâ€the tolerant ashes. The insubordinate nervous straination is a vastly mixed orchestra of cells working together to assist hand electric potencyly libelous pathogens from the body. Some form of host justification is raise in every cellular organism, gain there are myriad variatio ns in the resistant trunks of different organisms. Vertebrates apply build upd an acquired resistive rejoinder, in which a specific repellent arranging is worked up to light an transmitting that is initially control direct by a non-specific ( intrinsic) tolerant response.This highly admitable agreement is important to the selection of vertebrate species. Surprisingly, however, 90% of animals (invertebrates) do non retain this engaging of response. Despite lack a patently censorious adaptation, invertebrates continue to survive and reproduce. Why does it expect necessary for vertebrates to tolerate an acquired response in assign to survive, just now the much than than numerous invertebrate species do not? Research indicates that there is an growthary origination of the resistant strategy that stems from the split of invertebrates and vertebrates.Innate liberty, which is found in all animals, is assumed to be at the telegraph line of this evolutiona ry tree. After the diversification of species (vertebrates branching from invertebrates), mechanisms of immunity identically diverged. In this paper I impart first discuss the function of the innate insubordinate system because of its older evolutionary history, followed by the adaptational insubordinate response that evolved later in vertebrate blood lines. I entrust then conclude by placing the teaching of the innate and accommodative resistant system in an evolutionary context.Innate immunity is the first line of vindication for an organism and is made up of elements that hold dear the organism from pathogens. Anatomical aspects such as disrobe act as an impermeable barrier to infectious pathogens. Chemical and biological factors, including anti-microbial peptides like defensins, are similarly used to inhibit bacterial growth and forbid colonization. Another immunological factor of the innate tolerant system are phagocytic cells (macrophages), which are cells tha t launch and eliminate overseas pathogens.These cells operate using a variety of different and factorralized receptors that seduce it a sort a broad range of molecular patterns expressed by pathogens that initiate phagocytosis. One such family of receptors, kn birth as Toll-like Receptors, fill ins common pathogen elements such as bacterial mole comp mavinnts or viral DNA sequences. This comp angiotensin-converting enzyment is found in virtually every multicellular organism, ranging from sponges to valet (Muller and Muller 2003). Plants to a fault express proteins that are very similar to toll-like receptors, indicating that this aspect of the innate immune system predates the divergence of plants and animals.The innate immune system is so valuable to an organism’s survival because it is ceaselessly present and in umteen instances green goddess bear on pathogen entry or replication. This, in turn, prevents a harmful infection from ever occurring inside the host. Although invertebrates do not render the acquired immune response, recent research has sh let that their innate response is more complex than previously thought. Insects do-nothing activate their immune systems to remain in a higher state in say to lay for a pathogen invasion.During bedbug mating, females are frequently wound in the ferment because males get out stab a female to inject his sperm, infecting her with bacteria and exposing her to other capableness infections. In response, females stupefy evolved ways to enhance their immune system former to mating in foretelling of pathogen invasion (Morrow and Arnqvist 2003). Bumblebees are capable of maintaining a heightened immune system in response to a prior pathogen invasion to aid in the prevention of early infections. Immunity such as this has been shown to pass experience vertically to offspring, therefore increasing their fitness (Tyler et al. 006). Slugs stomach alike evolved an interesting alternative respons e in the form of extendd mutation rates of authoritative immune cell receptors, which allows their immune system to adapt to many foreign elements (Litman and Cooper 2007). eon it is inherently different from the acquired immune response, this sensitive management of immune function was previously thought to be dumb as a characteristic of vertebrates and the adaptative immune response. As vertebrates began to diverge and evolve from invertebrates, so as well as did the immune system.The natural reconciling branch of the immune system originally conferred a forward- beting discriminating advantage for vertebrates because of its specificity and immense flexibility in recognizing refreshed pathogens. The clonal selection theory, in which each lymphocyte clonally expresses a specific antigen receptor, send word tending excuse how the immune system shadow express an highly wide range of authorisation receptors capable of recognizing new pathogens. Lymphocytes are undiffe rentiated cells that ultimately become B-cells (B ace Marrow) or T-cells (Thymus) depending on where they migrate.B-cells possess a uniquely incorporated immunoglobulin molecule (antibodies exposed on outermost surface) that recognizes and prevails to a specific molecular counterpart. When a foreign antigen is bound to the antibody, it stimulates the replication of that specific B-cell with the aid of at disposeant T-cells, which enhance B-cell pus. This process results in the clonal combusting upon of cells that recognize the original antigen and subsequent doing of antibodies that help in the eradication of the pathogen. An important point of this process is that the pathogens select which lymphocytes expand.It also results in memory B-cells and T-cells that take a shit a persistent immune memory for a particular antigen. This expanded pool of memory cells is delirious upon a second exposure to the same pathogen, resulting in a much more rapid immune response to clear i nfection. Other types of T-cells are also produced during this process. For example, cytotoxic T-cells localize and kill virally infected cells, term suppressor or regulatory T-cells are activated when the infectious pathogens are eliminated and signal the immune system to subside.Cells such as these also experience discriminating tweetsâ€ones that react to self-tissue (and harm the host) would be selected against, mend those that recognize pathogens would survive and replicate. The clonal selection theory addresses many aspects of vertebrate immunity, however, it does not explain all of the mysteries bottom the variety of antibody generation. The sheer number of antibodies that can be produced and the finding that the acquired immune response can sire antibodies to manmade molecules that are not present in genius led scientists to explore how such form is generated.Research do by Susumu Tonegawa in the 1970’s indicated that B-cells have the skill to produce a h uge number of antibodies payable to a gene rearrangement process. B cells originally have many sets of gene segments (Variable, Diverse, and Joining) and over the course of its maturation reduce these segments to one of each type for the production of the antibody heavy kitchen stove. A similar process of gene rearrangement is involved for the production of the antibody light chain. The light chain and heavy chain proteins then assemble to form the complete antibody molecule that can specifically bind to an antigen.Two genes that are lively for this process to work are RAG1 and RAG2. These genes are known as recombination-activating genes and distinguish the vertebrate immune system from other melodic lines. These genes are exact to the process because they act as the excision and link molecules that cut and knit back together the several(prenominal) VDJ segments that furbish up up the antibody. This results in the huge potential of diverse antibodies that can be producedâ⠂¬hundreds of millions of possible antibody types generated from a much smaller number of gene segments that can react with virtually any antigen.This sophisticated process may have originally been introduced by a mobile genetic element known as transposons. These transposable elements have the ability to excise themselves from one DNA sequence and incorporate themselves into some other, very similar to the RAG1 and RAG2 gene functions. After the divergence of jawed and jawless vertebrates, a viral infection of the jawed lineage’s gametes may have introduced a transposon into their genome. (Thompson 1995). This may have provided the raw materials necessary to facilitate the development of adaptational immunity.The acquired response appears to have evolved from a single lineage because all vertebrates (excluding jawless fish) retain this RAG-mediated gene rearrangement system. The specificity of this kind of response may have been selected for because of its ability to rec ognize a diverse number of pathogens, only if also because it could conserve more energy resources compared to the generalized defense of the innate response. The adaptational immune response is unified in such a way that it can answer to an almost quad number of pathogens, while utilizing a relatively limited number of genes. experience 1 illustrates a potential phylogeny based on some immune system adaptations previously discussed. Figure 1 (Reproduced from Litman and Cooper 2007). Although the vertebrate immune system is extremely adaptable to many potential threats, it is furthest from undefiled. Epidemics such as the Bubonic Plague or the 1918 influenza killed millions of people. Similarly, when the Spanish colonized the New World, they also introduced pathogens that were devastating to the indigenous people.One of the major(ip) limitations of the acquired immune response is that it takes a relatively long time to respond after the initial exposure in order to be effecti ve. This time is required because the lymphocytes must clonally expand before a pathogen can be eliminated. For example, in the event of the Native Americans, when they were exposed to the new pathogens, the infections overspread to a portion of the population that was giant full to leave them unable to forage for food or to tend to the sick. As a result, it nearly wiped out the full civilization.This limitation is significant as illustrated by these and many other historical epidemics. These difficulties have led scientists to think more fully about the military posture of the vertebrate immune system. If the immune system has the potential to combat virtually any conceivable threat, why then can’t it always eliminate any potentially harmful pathogen? We also look to immune hypersensitivity and autoimmunity as potential drawbacks of the immune system, indicating further imperfections of the adaptation. When the immune system misinterpretedly targets self-tissue, it res ults in spartan consequences for the organism.Concepts in evolutionary biology might help address these issues. In this context the immune system does not have to be inherently perfect by design because only some individuals of a population need to survive and reproduce for that lineage to continue. The variation introduced by the immune system generates the diversity necessary for a population to adapt to ever-changing environmental pressures. As others have suggested, a zebra doesn’t have to outrun the lion, just the slowest component of the herd (Hedrick 2004).The immune system is subjected to the same constraints as other characteristics in regards to natural selection. In this case even if a trait is not optimal, but helps the organism survive and reproduce, it will be selected for, careless(predicate) of any deleterious effects experienced post-reproduction. Many, but not all immunologists, believe the development of the adaptive immune system with gene rearrangement was a critical advance. It has been proposed that the development of the adaptive immune system was the â€Å" boastful Bang” for the evolution of immune system (Travis 2009).This development might have also enabled the rapid working out of vertebrates. Moreover, the idea that the adaptive immune system can generate receptors for molecules that are not yet present, makes it extremely flexible and has been called â€Å"forward thinking” (Travis 2009). so, while the immune system does not anticipate every transpose in organisms it is ready for them by constructing a large repertoire of antigen specific receptors, which confers a big selective advantage. Others have suggested the adaptive immune system conserves resources, and thus is better than the innate system.In contrast, as celebrated earlier, invertebrates lack a fully functional adaptive immune system and are very successful. Moreover, others have argued that even if the immune system was an advantage, it wa s only terminable and short lived (Hedrick 2004). Another relevant issue deals with the image of parasite and host co-evolution. This constant struggle is exemplified by a quote from Lewis Carroll’s â€Å"Through the looking for Glass”, â€Å"it takes all the running you can do, to deliver in the same place”. This concept, originally introduced by Leigh Van Valen, has been termed the Red Queen hypothesis.According to this hypothesis, an improvement in fitness for one species will lead to a selective advantage for that species. However, since species are often coevolving with one another, improvement in one species implies that it gains a militant advantage over the other species, and thus has the potential to outcompete for shared resources. This content that fitness increase in one evolutionary system will tend to lead to fitness decrease in another system. The only way that a competing species can maintain its relative fitness is to improve on its own des ign.Although this theory was used to help explain the liquidation of species and the evolution of sexual reproduction, it has been applied to many aspects of vulture prey relationships including the development of the immune system. Because animals are constantly attacked by fast-adapting parasites, the host immune system cannot possibly gain an advantage over them. The evolution of the immune system is caused by the small advantages conferred as a result of variation in the recognition of pathogens.As suggested by Steven Hedrick, â€Å"by selecting for more elusive parasites, the immune system is ultimately the cause of its own necessity” (Hedrick 2004). therefore paradoxically, the immune system, since it places a strong selective pressure on pathogens and parasites, ultimately has become essential for vertebrates to survive. By placing selective pressure on parasites that can evolve much more rapidly than animals (due to their higher productive/mutation rate), it resu lts in parasites that are increasingly more effective at infecting hosts of that species.In terms of the immune system, one strategy that parasites have developed is a instrument of altering their own antigens to become unrecognizable. In this way they escape the adaptive immune system by altering their structure. For example, trypanosomes can switch the major target antigen for antibodies, which they use as a strategy to pop the question the amount of time they reside in the host. This results in a more contagious host that will increase the spread of pathogens to new hosts (Stockdale et al. 2008).Similarly, because the HIV polymerase is very error prone with no proof rendition mechanism, many mutations arise in the HIV proteins during its infection. While the adaptive immune system can make neutralizing antibodies, new variants arise that can no longish be recognized by the antibodies. These new variants have a selective advantage and escape, and thus the adaptive immune syste m is always lagging behind. In terms of the host immune response, there is also an extremely high level of polymorphism of major histocompatibility genes, which enable the population to respond to a wider array of antigens using T-cells.The benefit of this heterozygosity is that it allows the individual to respond to a wider variety of antigens. Moreover this diversity helps ensure that even though some individuals may perish, the particular pathogen will not be able to eliminate the entire population. Some infectious agents have even taken it a step further and evolved ways to use the host immune system to increase their own fitness. For example, infections that result in pus filled cysts can be used to carry parasitic payoff and spread to new hosts when they burst.Even though this may help the host clear an infection, the pathogen can use this to increase its own fitness and infect more individuals. The military man Immunodeficiency Virus (HIV) utilizes the host immune sy stem by initially infecting macrophages, and subsequently T-cells, which the virus uses as a reservoir for reproduction and as a means to spread to many different tissues in the body (Orenstein 2001). It also serves the virus to target immune cells for infection because crippling the host immune response akes it easier for the virus to spread throughout the body and eventually to new hosts (due to the higher viral load). In this light, it is possible that invertebrates did not evolve the adaptive immune response because they may have never needed it. By lacking the ability to develop a â€Å"memory” for a particular pathogen, those pathogens did not evolve anti-immune mechanisms to counter the host immune response. An immune memory could lead to more devious pathogens and result in a more harmful infection in the future.This could have been a better strategy for invertebrates as it may have prevented the co-evolution of more virulent pathogens (Hedrick 2004). The immune syste m has a long evolutionary history in multicellular organisms. The innate immune system is a critical adaptation that helped these organisms survive the onslaught of parasites and pathogens. Vertebrates possess an adaptive immune response that allowed for the recognition of an almost infinite number of pathogenic antigens, however, it appears to have become a one-way road with the coevolution of pathogens.Once this adaptive system appeared in the vertebrate lineage, there was no going back. Because of the immense flexibility of the adaptive immune response, it places huge selective pressures on pathogens to constantly evolve new mechanisms of infecting hosts. Thus in the context of evolution, even with the incredible versatility of the adaptive immune system, it is likely there can not be an ultimate solution to infection by parasites only a new, perhaps unstable, equilibrium. Works Cited Hedrick, S. (2004). The Acquired tolerant System: A Vantage from Beneath.Immunity 21, 607-615. Litman, G. and Cooper, M. (2007). Why analyse the Evolution of Immunity? Nature Immunology 8, 547-548. Morrow, E. H. , and Arnqvist, G. (2003). Costly traumatic insemination and a female counter-adaptation in bed bugs. proceedings of the Royal SocietyB: Biological Sciences. 270: 2377â€2381 Muller, W. and Muller, I. (2003). Origin of the Metazoan Immune System: Identification of the Molecules and Their Functions in Sponge. Integrative and Comparative biological science 43, 281-292. Orenstein, J. (2001). The Macrophage in HIV Infection.Immunobiol. 204, 598- 602. Stockdale, C. , Swiderski, M. , Barry D. , and Richard McCulloch (2008). Antigenic Variation in Trypanosoma brucei: Joining the DOTs. PLoS Biol 6. Thompson, C. B. (1995). New insights into V(D)J recombination and its role in the evolution of the immune system. Immunity 3, 531â€539. Travis, John. (2009). â€Å"On the Origin of the Immune System”. Sciencemag Vol. 329. Tyler, E. , Adams, S. , and Mallon, E. (2006) , An Immune Response in the Bumblebee,Bombus terrestris leads to increase food consumption. BMC Physiology 6.\r\n'