Jennifer Rough Draft

Evolution of the Acquired Immune System
Jennifer Cardonick, 2008
Immunology/ Dr. Robson

INTRODUCTION
The body is an amazing try to use another word instead of amazing network of interactions within itself, always on high alert protection from invading microbes, pathogens and other harmful substances. (Consider: Our immune system is an amazing network of interactions that is always on high alert from invading microbes, pathogens, and other harmful substances.) The immune system consists of a nonspecific, innate system, which is present at birth and a specific, acquired IMMUNE system, (AIS) which evolved as a result of the innate immune system. Both immune systems have evolved over time to work intimately with each other in order to fight off infections. Exactly how these systems evolved into a working pair is an enigma and has been theorized over the years (10). (maybe add something about the importance of the immune system such as without it people would die very young and more diseases would exist) It may be important to mention that the acquired immune system is limited to mammals (I believe). It may be useful to compare and contrast the innate immune system present in "lower animals" like bugs or something to "higher animals" like mammals.

Because (Since) the events of the ancient past cannot be replicated, we have only been left with speculation that havehas produced many theories. However, to understand the evolution of the AIS several studies were performed on the genome of an opossum (I know this is used later, but it seems out of place here.). (1) More studies were conducted on survivors, including their descendants, of events that have occurred in more recent history, such as Chernobyl, the Holocaust (,) and Vietnam. These studies have given rise to three of the more popular theories: stress, parasitic relationship, and environmental factors. This is a really good introduction to your theories, but you should put this signposting by your theories and not before you background section. You should think to have a longer introduction. It is good that you mention the theories but you should explain them a little bit more
OVERVIEW OF THE NONSPECIFIC, INNATE IMMUNE SYSTEM AND THE SPECIFIC, ACQUIRED IMMUNE SYSTEM
Because of the Since there is a close interactions between the two immune systems, it is important to understand the foundational innate immune system and its relationship to the AIS. The nonspecific, innate immune system is present at birth and includes such barriers such as the skin, mucus membranes, tears (,) and saliva. This system does not discriminate among foreign invaders of the body; therefore, its response is a much more rapid one, occurring within minutes to hours of an attack. Its trademark consists of inflammation which is caused by phagocytosis, the complement cascade, collectins and cytokines. (Is inflammation caused by all of these? or is it mainly just cytokines?) Explain a little bit more
A further breakdown of the innate immune system includes phagocytosis, and these (which) may have had an important hand in the evolution of more specialized immune and neuroendrocrine related molecules in the AIS. (10) Neutrophils, macrophages and monocytes make up the phagocytes (are monocytes phagocytes, or do they differentiate into macrophages, which are phagocytes) and are responsible for the engulfment and ingestion of foreign substances such as bacteria. When monocytes leave the blood in order to reside in a specific area of the body, they then become macrophages. Try to reword it (First, I would consider deleting this sentence, however if you were to keep it, i suggest it reading "Monocytes leave the blood and reside in specific body tissure where they differentiate into macrophages") According to Ottaviani and Franceshi, 1998, these macrophages then became specialized evolved mechanisms within their new surroundings, providing the body protection from foreign substances. It is speculated that these macrophages have evolved over time creating the AIS. (2, 3, 7) (author names are not important in writting since the reference would tell the reader where the information came from if they wanted to know) Remember that if you are using the exact words as the authors you have to quote, if not try to write it in your own words :)
The AIS is antigen specific, meaning that the body recognizes a particular foreign substance and selectively reacts to it. (6) (Consider: The AIS is antigen specific in which the body recognizes..) The AIS is mediated primarily by lymphocytes, which are a family of immune cells and the primary cells involved in the AIS. These lymphocytes that divide the AIS into two complex, highly specific categories, which are the humoral and cellular immune responses. The humoral immune response’s principle products are immunoglobulins, also known as antibodies, which that are produced by B cells. These B cells are derived from the bone marrow and differentiate into plasma cells and memory cells. The plasma cells then secrete proteins known as antibodies. (May want to add a little bit about the memory cells) (You have defined antibodies in two different ways maybe a clarification would be nice) The cellular immune response deals more with the T cells, which are produced from the thymus, located at the base of the neck. The thymus is a starts as very large organ in the young, but shrinks after puberty (Is this sentence necessary?) (Try to reword this sentence if not you should think to delete it). It is a very important organ because it try to avoid the it regulates many different areas of the body, including helping the immune system develop development of the immune system. (Does it develop the whole immune system? or does it act as a place for our part of our immune system to grow and develop?) As shown in Good and Dalmasso 1962 paper, when the thymus was removed from a neonatal mouse, its ability to develop an immune system was hampered, completely disallowing it to form antibodies against the bacteriophage T2.(more information of what baceriophage T2 is) However However acts as a contradictory introduction, but the following statement is a supportive statement, when 5 day old rabbits had a complete thymectomys, they produced an immunologic deficiency as adults and had reduced antibody production to bovine serum albumin and bacteriophage T2. When a thymus was transplanted back into the rabbit, immunity was unaffected. Try to explain the importance and relationship of this towards human Expand on the what this means to us, why is it important to note that implanting a thymus does not help the development of T-cells (24)
Another hypothesis of local T cells is that they are made in gut-associated lymphoid tissues (GALT), suggesting that the thymus and GALT have similar functions and may be evolutionarily related. It is also hypothesized that the thymus may have evolved from mucosa-associated lymphoid tissues (MALT), located in the gill region in early vertebrates as shown in( Figure 1, 17) It is hypothesized because of the GALT that the relationship between the gut epithelium, lymphocytes, and the cryopatches is how the thymus evolved. Migrating from the cortex to the medulla through the epithelial network, these thymocytes originate from the bone marrow. (17) Figure 2 also shows a demonstration of how the thymus may have evolved. (17)

Fig. 1. (A) Creation of the thymus in the lamina propria of mouse intestines. It is hypothesized that there is a strong correlation betwee the gut epithelium , lymphocytes and the cryptopatches (●). CP, the cryptopatches; IEL, intraepithelial lymphocytes; LPL, lamina propria lymphocytes. (B) The thymus. The relation between the thymus epithelium and lymphocytes is shown. The thymus epithelium is illustrated by star-shaped cells and the thymocytes are shown by round cells in (●). Thymocytes that originated from bone marrow migrate unidirectionally from the cortex to the medulla through the epithelial network. (17)

Fig. 2. The sequence of evolution of the thymus. Reticular epithelium began to form around and in the cryptopatches located in gill-associated mucosa (A–C). The composite mixture of cryptopatch-epithelial cell further enlarged and eventually formed a structure surrounded by connective tissue (D). This structure eventually segregated from the mucosal epithelium (E). GC, gill cavity; GE, gut epithelium; CP, the cryptopatches. (17)

UNDERSTANDING THE IMMUNE SYSTEM THROUGH THE GENOME OF A OPOSSUMS
Belov and Sanderson, 2007 (1), who did a study on the genome of opossums, noticed that the opossums are born with no immune response at all, but the opossums' immune systems evolved over time because of pathogens and parasites within their environment. When comparing the immune systems of opossums and eutherians, it is evident that the opossum's babies have no adaptive immune system while eutherian young are born with a relatively well- developed adaptive immune system. Opossums also do not pass on any antibodies through their placenta and or milk after the young is born, but they do rely on passive immunity from lactation for 16 days;. After 16 days, the young have a 20 day period of intermittent suckling as they are exposed to pathogens and others parasites. (1)
THEORY #1, STRESS
By tracing the survivors and descendants who have lived through stressful situations, scientists may be able to piece together the intricate way the immune systems work together. It is because of these studies involving Vietnam veterans that the pieces of the past concerning the evolution of the two immune systems can be understood. One of the more popular theories is that stress could have easily been a factor which lead to the adverse and multifaceted AIS many people take for granted today. In the study of the Vietnam veterans, it was proven that modifications had been made to their AIS. It has been well documented that those who fought in Vietnam not only showed signs of post- traumatic stress disorder (PTSD), but they also have abnormal levels of leukocytes and lymphocytes. Many of their descendants also have abnormal levels of leukocytes and lymphocytes. (21) As shown in Table 1, the lymphocytes and leukocytes are much higher in veterans with PSTD than those without. (21) Since lymphocytes are the primary cells involved in the AIS, these veterans with altered levels may suffer many different types of medical disorders. (21) is there any other explanation for this finding?
Laboratory Testa Current PTSD
________
No PTSD (%)
________ PTSD (%)
________ Crude OR
________ Adj. OR
________ Adj. OR 95% CI
________ p
________
White blood cells (>11,000/mm3) 2.9 6.1 2.22d 1.83c (1.03–3.25) .040
Total lymphocytes (>3000/mm3) 4.4 7.5 1.78c 1.44 (0.86–2.41) .171
B-cell count (>370/mm3) 20.4 22.2 1.11 0.93 (0.67–1.28) .662
T-cell count (>2640/mm3) 3.0 6.1 2.15d 1.82c (1.01–3.26) .045
CD4 count (>1800/mm3) 3.8 6.5 1.74c 1.62 (0.94–2.82) .085
CD8 count (>1220/mm3) 2.4 5.1 2.18c 1.80 (0.97–3.35) .062
CD4/CD8 ratio (>2.60/ratio) 14.9 19.1 1.35 1.33 (0.96–1.84) .089
CMI skin testb 7.7 6.8 0.88 0.86 (0.53–1.41) .550
N
________ 2179
________ 286
________ ________ ________ ________ ________
Table 1. Vietnam statistics with PTSD. When comparing those veterans with PSTD and those without it, all the lymphocytes and leukocytes are higher in those veterans with PSTD. http://www.psychosomaticmedicine.org/cgi/content/full/61/3/378

THEORY #2, PARASITIC RELATIONSHIPS
Parasitic relationships have also had a significant impact on the evolution of the host’s immune systems. “Survival of the fittest” has a large impact on the struggle between the host immune system and the pathogens or parasites that readily want to compromise it. While parasites and other pathogens evolve to their environment in order to survive, so does the host in order to compete with the ever-changing pathogens and parasites. (12,13) As earlier mentioned in the section of the genome of an opossum, parasites and pathogens play an important role a large part in the evolution of the acquired immune system because without them the AIS wouldn’t (would not) be able to evolve and develop. (what is this role?)*8
THEORY #3: ENVIRONMENTAL FACTORS
The third theory which has a substantial hold (
consider grip) **(or support)on the evolution of the AIS is that environmental factors have played an important role; perhaps, playing an even more important role than the other two theories. Since it is almost impossible to know exactly what happened to the immune systems of ancestors who lived thousands to millions of years ago, the well documented studies of events which occurred in current history enable scientists to pinpoint causes that may have led to the many different phases of the evolution of the AIS. The radiation caused by Chernobyl (16) (The radiation was not "caused" by chernobyl… I suggest saying something like…"The radiation evident in the Chernobyl tragedy…) and the dioxin contained in Agent Orange (23) have had significant effects on the immune system by significantly mutating the AIS’s abilities into the system it is today. Since the beginning of time, we (Do not use we in this paper)(Use humans instead) have coexisted with low doses of radiation and chemicals. If large amounts of radiation and harmful chemicals from Chernobyl and herbicides containing dioxin caused obvious signs of birth defects, meaning there was a higher incidence of mutations within the genomic makeup, it would be insensible to not think that natural radiation and chemicals would not do the same. (Consider revising sentence to make it shorter and flow better) what about other factors?
As seen in Figure 3, a young boy was born with many birth defects because of the explosion of radioactive material in Chernobyl. While his defects are outwardly apparent, the mutations in the AIS are not so apparent, but, as stated above, it would be likely, since all animals have been living with natural radioactive materials and chemicals since the beginning of time, that over time the AIS has obviously mutated in order to protect the body against harmful agents.

Figure 1: Birth defect because of Chernobyl. Radioactive waste was spread over many parts of Russia, causing residents to suffer high levels of cancerous tumors and many of their children were born with birth defects. http://pixelpress.org/chernobyl/index.html

Jennifer- You have good information and the transition of your paragraph so far sound good the only thing that you have to be aware of is that there are some words that I did not understand as a reader. Also remember that if you wrote the exact words as the person that did the research you need to quote it or try to reword it but do not forget to put the citation at the end. The theories as you start mentioning on the paper need a little bit of more explanation you should go a little deeper in that. And about the images I do not know if its because is in here in wiki but I couldn't be able to understand them.. Good Luck!!!
Jennifer- I like the way you have organized your paper. The transition between the first two paragraphs are the only organizational problems I found. Since the theories on the evolution of the acquired immune system seems to be the main focus of your paper, i would include more examples and more details under each theory (if you can find the information). Also a conclusive paragraph restating the importance of both the innate and acquired immune system and discussing the problems with each of the theories and/or problems with trying to find the evolution of the acquired immune system. You have a good start!!
Jennifer-Your topic is interesting, but i think you need more information. The structure of the paper is great, and for the most part it reads well. I would also suggest putting in more information on both the innate and acquired immune system.

Jennifer- I had a hard time reading your tables… You may want to dummy it down for your audience or even take it out. I really don't see how the raw data helped your reader out, a simple sentence stating the results with citation if the reader wants to see the raw data would be sufficient. I want to know more about the innate and acquired immune system as well. The paper doesn't appear to have much of an ending, a strong conclusion tying everything you said together would be nice.

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