Cardiac inflammation associated with a Western diet is mediated via activation of RAGE by AGEs: http://ajpendo.physiology.org/cgi/content/short/295/2/E323
19 September 2008
During our first discussion about Type II Diabetes and its relation to inflammation we spent quite a bit of time talking about diet. As this subject continued to come up I was constantly reminded that the issue was not entirely about subjective decision making but also had many social implicatiaions. One factiod that stuck in my mind was that inflammatory factors stay elevated for up to four hours after eating fast food. Well I found this article that specifically focuses of the inflammatory effects of the "Western Diet" and wanted to share it and wanted to know what you all thought about the increasing importance of AGEs and AGE receptors.
17 September 2008
I came across a recent article in science which described how certain type of cells within the thymus that express autoimmune regulators (AIRES) that act as safety net for eliminating autoreactive immune cells.
Science 8 August 2008:Vol. 321. no. 5890, pp. 776 - 777DOI: 10.1126/science.1162966
Prev Table of Contents Next
Perspectives
IMMUNOLOGY:A Breath of Aire for the PeripheryBruno Kyewski*
The term "self-tolerance" encompasses all mechanisms that protect the body against attack by its own immune system. The adaptive arm of the immune system generates immune cells that express antigen-specific receptors by a random mechanism that requires quality control--selecting a "personalized" repertoire of receptors directed against foreign but not self-antigens (1). Central and peripheral tolerance to self are distinguished according to the site where tolerance is imposed (2). Central tolerance for T lymphocytes occurs in the thymus, where their primary antigen receptor repertoire is generated. Here, developing T cells that recognize and react to self-antigens are eliminated or diverted into T regulatory cells that suppress activation of the immune system and prevent self-reactivity. Although the thymus displays a vast array of self-antigens, including those whose expression is otherwise restricted to specific tissues, this collection is nevertheless incomplete. On page 843 of this issue, Gardner et al. (3) report how peripheral lymphoid tissues act as a safety net, preventing T cells specific for antigens not presented in the thymus from escaping elimination.
Medullary thymic epithelial cells, a particular thymic stromal cell type, express a diverse set of genes that are otherwise restricted to certain tissues and/or stages of development (4). This so-called promiscuous gene expression in the thymus is partly regulated by a transcriptional regulator called the Autoimmune regulator (Aire). Mice deficient in Aire develop a multi-organ autoimmune syndrome, similar to that of humans with functional mutations in the Aire gene (5).
Aire is highly expressed in thymic medullary epithelial cells. However, the functionally relevant expression of Aire in cells of peripheral lymphoid organs has been controversial (5-9). Gardner et al. now identify cells in peripheral lymph nodes, spleen, and Peyer's patches (lymphoid structures of the gut), that express Aire and mediate deletion of auto-reactive T cells. The authors genetically engineered mice in which the promoter of the Aire gene drives expression of a fusion protein composed of green fluorescent protein and islet-specific glucose-6-phosphatase related protein (Igrp), an antigen specific to the pancreas. Of the medullary thymic epithelial cells and peripheral cells that expressed the reporter protein, 85% and 25% expressed endogenous Aire, respectively. Most of these peripheral cells, called extrathymic Aire-expressing cells, were stromal-type epithelial cells, located at the interface between T and B cell areas in peripheral lymphoid tissues. These cells also expressed receptors characteristic of antigen-presenting cells, but differed in several markers from the medullary epithelial cells in the thymus. Surprisingly, some of these extrathymic Aire-expressing cells were highly mobile within the lymph node microenvironment, and at the same time were able to delete T cells specific for the reporter protein.
Complementary tolerance. The transcriptional regulator Aire controls the expression of complementary pools of self-antigens in the thymus and peripheral lymphoid tissues that sequentially imprint central and peripheral T cell tolerance, respectively.
CREDIT: C.BICKEL/SCIENCEPerhaps the most intriguing result of this study relates to the target genes controlled by Aire in the thymus versus the periphery. The number of genes in the latter is about one-tenth of that in the thymus, and their degree of Aire-dependent regulation is less pronounced. Moreover, although there is little overlap between the gene pools, both are clearly enriched in genes encoding for tissue-restricted self-antigens (see the figure). The distinct composition of both gene pools favors a role for peripheral tolerance that is complementary to tolerance developed in the thymus. A recent study by Lee et al. also identified a fraction of nonhematopoietic cells in mesenteric lymph nodes that express Aire and certain tissue-restricted self-antigens, and mediates peripheral T cell deletion (9). However, these cells were less rigorously enriched, and differed phenotypically, compared to those identified by Gardner et al. Moreover, the data of Lee et al. are more in line with the concept that peripheral tolerance serves as a backup for central tolerance rather than being complementary.
The study by Gardner et al. still leaves some important questions that need to be answered before a definitive role can be assigned to Aire in peripheral tolerance. Why do only 25% of peripheral cells in the transgenic mice that express the fluorescent reporter protein also express endogenous Aire? Is it due to ectopic expression of the reporter construct in otherwise Aire-negative cells? Is endogenous expression of Aire too low to be detected, or is expression of Aire and the reporter protein not synchronized? The relatively low concordance between the reporter and endogenous Aire expression may also contribute to the apparently relatively low degree of gene expression induced by Aire in the peripheral cells, which for most genes is less than twofold compared to the background expression in Aire-deficient mice.
Although tolerance induction is thought to be exquisitely sensitive to low numbers of self-antigens that are presented to T cells in the context of the major histocompatibility complex, it will be essential to show that the low expression level of endogenous tissue-restricted self-antigens in peripheral Aire-expressing cells are "tolerogenic." After all, at first glance, the autoimmune phenotype of Aire-deficient mice was fully reproduced by transplanting Aire-deficient thymic stromal cells (with no functional evidence for Aire in extrathymic sites) (5). Given the different composition of self-antigens displayed in peripheral cells, the autoimmune phenotype caused by lack of Aire in the periphery may have been subtle and previously overlooked. Notwithstanding these caveats, the study by Gardner et al. raises intriguing questions about the role and function of Aire and the nature of the peripheral cells that express this factor (10).
The emergence of the extrathymic Aire-expressing cells in vertebrates is interesting, given that organized secondary lymphoid organs evolved much later than the thymus (11). Aire is a single-copy gene with orthologs in mammals, birds, and fish whose structure has been conserved in vertebrates over more than 400 million years (12). No ancestral Aire genes have been reported in invertebrates. This suggests that Aire and its role in tolerance were acquired early during vertebrate evolution, most likely concurrent with the emergence of the adaptive immune system. One question is whether Aire's only role is to ensure central tolerance, or whether it has been coopted for other functions. The study by Gardner et al. now presents a strong argument in favor of the latter--Aire also seems to contribute to establishing peripheral tolerance.
Science 8 August 2008:Vol. 321. no. 5890, pp. 776 - 777DOI: 10.1126/science.1162966
Prev Table of Contents Next
Perspectives
IMMUNOLOGY:A Breath of Aire for the PeripheryBruno Kyewski*
The term "self-tolerance" encompasses all mechanisms that protect the body against attack by its own immune system. The adaptive arm of the immune system generates immune cells that express antigen-specific receptors by a random mechanism that requires quality control--selecting a "personalized" repertoire of receptors directed against foreign but not self-antigens (1). Central and peripheral tolerance to self are distinguished according to the site where tolerance is imposed (2). Central tolerance for T lymphocytes occurs in the thymus, where their primary antigen receptor repertoire is generated. Here, developing T cells that recognize and react to self-antigens are eliminated or diverted into T regulatory cells that suppress activation of the immune system and prevent self-reactivity. Although the thymus displays a vast array of self-antigens, including those whose expression is otherwise restricted to specific tissues, this collection is nevertheless incomplete. On page 843 of this issue, Gardner et al. (3) report how peripheral lymphoid tissues act as a safety net, preventing T cells specific for antigens not presented in the thymus from escaping elimination.
Medullary thymic epithelial cells, a particular thymic stromal cell type, express a diverse set of genes that are otherwise restricted to certain tissues and/or stages of development (4). This so-called promiscuous gene expression in the thymus is partly regulated by a transcriptional regulator called the Autoimmune regulator (Aire). Mice deficient in Aire develop a multi-organ autoimmune syndrome, similar to that of humans with functional mutations in the Aire gene (5).
Aire is highly expressed in thymic medullary epithelial cells. However, the functionally relevant expression of Aire in cells of peripheral lymphoid organs has been controversial (5-9). Gardner et al. now identify cells in peripheral lymph nodes, spleen, and Peyer's patches (lymphoid structures of the gut), that express Aire and mediate deletion of auto-reactive T cells. The authors genetically engineered mice in which the promoter of the Aire gene drives expression of a fusion protein composed of green fluorescent protein and islet-specific glucose-6-phosphatase related protein (Igrp), an antigen specific to the pancreas. Of the medullary thymic epithelial cells and peripheral cells that expressed the reporter protein, 85% and 25% expressed endogenous Aire, respectively. Most of these peripheral cells, called extrathymic Aire-expressing cells, were stromal-type epithelial cells, located at the interface between T and B cell areas in peripheral lymphoid tissues. These cells also expressed receptors characteristic of antigen-presenting cells, but differed in several markers from the medullary epithelial cells in the thymus. Surprisingly, some of these extrathymic Aire-expressing cells were highly mobile within the lymph node microenvironment, and at the same time were able to delete T cells specific for the reporter protein.
Complementary tolerance. The transcriptional regulator Aire controls the expression of complementary pools of self-antigens in the thymus and peripheral lymphoid tissues that sequentially imprint central and peripheral T cell tolerance, respectively.
CREDIT: C.BICKEL/SCIENCEPerhaps the most intriguing result of this study relates to the target genes controlled by Aire in the thymus versus the periphery. The number of genes in the latter is about one-tenth of that in the thymus, and their degree of Aire-dependent regulation is less pronounced. Moreover, although there is little overlap between the gene pools, both are clearly enriched in genes encoding for tissue-restricted self-antigens (see the figure). The distinct composition of both gene pools favors a role for peripheral tolerance that is complementary to tolerance developed in the thymus. A recent study by Lee et al. also identified a fraction of nonhematopoietic cells in mesenteric lymph nodes that express Aire and certain tissue-restricted self-antigens, and mediates peripheral T cell deletion (9). However, these cells were less rigorously enriched, and differed phenotypically, compared to those identified by Gardner et al. Moreover, the data of Lee et al. are more in line with the concept that peripheral tolerance serves as a backup for central tolerance rather than being complementary.
The study by Gardner et al. still leaves some important questions that need to be answered before a definitive role can be assigned to Aire in peripheral tolerance. Why do only 25% of peripheral cells in the transgenic mice that express the fluorescent reporter protein also express endogenous Aire? Is it due to ectopic expression of the reporter construct in otherwise Aire-negative cells? Is endogenous expression of Aire too low to be detected, or is expression of Aire and the reporter protein not synchronized? The relatively low concordance between the reporter and endogenous Aire expression may also contribute to the apparently relatively low degree of gene expression induced by Aire in the peripheral cells, which for most genes is less than twofold compared to the background expression in Aire-deficient mice.
Although tolerance induction is thought to be exquisitely sensitive to low numbers of self-antigens that are presented to T cells in the context of the major histocompatibility complex, it will be essential to show that the low expression level of endogenous tissue-restricted self-antigens in peripheral Aire-expressing cells are "tolerogenic." After all, at first glance, the autoimmune phenotype of Aire-deficient mice was fully reproduced by transplanting Aire-deficient thymic stromal cells (with no functional evidence for Aire in extrathymic sites) (5). Given the different composition of self-antigens displayed in peripheral cells, the autoimmune phenotype caused by lack of Aire in the periphery may have been subtle and previously overlooked. Notwithstanding these caveats, the study by Gardner et al. raises intriguing questions about the role and function of Aire and the nature of the peripheral cells that express this factor (10).
The emergence of the extrathymic Aire-expressing cells in vertebrates is interesting, given that organized secondary lymphoid organs evolved much later than the thymus (11). Aire is a single-copy gene with orthologs in mammals, birds, and fish whose structure has been conserved in vertebrates over more than 400 million years (12). No ancestral Aire genes have been reported in invertebrates. This suggests that Aire and its role in tolerance were acquired early during vertebrate evolution, most likely concurrent with the emergence of the adaptive immune system. One question is whether Aire's only role is to ensure central tolerance, or whether it has been coopted for other functions. The study by Gardner et al. now presents a strong argument in favor of the latter--Aire also seems to contribute to establishing peripheral tolerance.
tobacco
it was interesting that tobacco plant is used for making antibodies. IS this because tobacco is one of the plants which can be regenerated froma single cell. Can potatoe plants be used for this purpose. i have heard taht they can also be regenerated from a single cell
14 September 2008
Obesity and Diabetes
I just wanted to give a brief overview of how obesity, inflammation, and type 2 diabetes are related for this week’s class. After reading a few research articles on the subjects I found that obesity essentially causes chronic inflammation. This has been verified in studies by high plasma concentrations of molecules such as tumor necrosis factor, interleukin-6, and C-reactive protein. In fact, it is the adipose tissue itself that acts like an organ and secretes hormones and cytokines that can cause this inflammation. The resulting chronic inflammation has been found to be the cause of insulin resistance and type 2 diabetes. Since this is a relatively new subject in science, the exact mechanisms and causes are not fully understood and are currently being investigated.
http://www.idf.org/home/index.cfm?unode=c659495d-7467-45c0-8a19-5b3d8ea3d172
I came across this article while searching for more information on diabetes and obesity. The article comes from the International Diabetes Foundation. Some of the statistics in it are extremely alarming. For example, the article states that diabetes and other diseases that result from obesity are responsible for more deaths annually worldwide than AIDS. It also explained that obesity and diabetes caused by obesity are worldwide epidemics. I may be alone in this, but I always envisioned obesity and resulting health problems to be more prominent in the US and parts of Europe. However, the article states that it’s becoming a major problem in “low to moderate income countries” like South Africa, Egypt, and Mexico. The article really conveys a sense of urgency and calls for a worldwide effort to change diets and lifestyles. I’m just curious to hear everyone’s views on the matter. What do you think?
Finally, I was wondering if anybody was able to come across any information on how to effectively screen for this “silent inflammation.” I know blood tests can reveal markers like C-reactive protein but as the previous post states, C-reactive proteins do not indicate inflammation exclusively.
http://www.idf.org/home/index.cfm?unode=c659495d-7467-45c0-8a19-5b3d8ea3d172
I came across this article while searching for more information on diabetes and obesity. The article comes from the International Diabetes Foundation. Some of the statistics in it are extremely alarming. For example, the article states that diabetes and other diseases that result from obesity are responsible for more deaths annually worldwide than AIDS. It also explained that obesity and diabetes caused by obesity are worldwide epidemics. I may be alone in this, but I always envisioned obesity and resulting health problems to be more prominent in the US and parts of Europe. However, the article states that it’s becoming a major problem in “low to moderate income countries” like South Africa, Egypt, and Mexico. The article really conveys a sense of urgency and calls for a worldwide effort to change diets and lifestyles. I’m just curious to hear everyone’s views on the matter. What do you think?
Finally, I was wondering if anybody was able to come across any information on how to effectively screen for this “silent inflammation.” I know blood tests can reveal markers like C-reactive protein but as the previous post states, C-reactive proteins do not indicate inflammation exclusively.
Obesity and Inflammation
Hello everyone!!
I have read the obesity/diabetes articles and I want to share some ideas from the articles that I found interesting (but you don't have to).
In the articles "Obesity and the Flu", "Visceral Fat Pronounced Guilty of Systemic Inflammation" and "In Diabetes, a Complex of Causes", visceral fat/skeleton was labled as an endocrine organ. I recently heard that fat had a metabolic function, but I did not know that it was therefore classified as an organ. This is a relatively recent discovery in the scientific world, and will provide new hypotheses for years to come.
In our last class, on Monday, September 8th, we discussed a short article titled, "The Inflammation Age" from Better Nutrition. At the end of this article, it suggested that a simple blood plasma test that investigated levels of CRP (C-reactive protein) was the best tool to understand your risks of inflammation. However, Zoe pointed out to the class that the method may be skewed. Why do many of the articles given to us about obesity/diabetes and the relationship with diabetes suggests that levels of CRP can be an efficient way of detecting inflammation? After further investigation, I gathered that abnormal CRP levels can be the consequence of different things, such as viral infections and liver failure. Therefore, this test proves to not be very specific. As Zoe mentioned, this test may not accurately detect what we are looking for.
In addition to the above, I would like to pose a question for the future. What do you think is the most efficient way to treat obesity and diabetes? There have been multiple medications that have been tested and used. Exercise and diet have been tried countless times. Different surgical methods have been discovered and performed. I think that since all of the treatments have various routes, diverse side effects and risks, and distinct goals, it is very hard to compare them. Maybe each patient has a "best" treatment for themselves and their condition.
I have read the obesity/diabetes articles and I want to share some ideas from the articles that I found interesting (but you don't have to).
In the articles "Obesity and the Flu", "Visceral Fat Pronounced Guilty of Systemic Inflammation" and "In Diabetes, a Complex of Causes", visceral fat/skeleton was labled as an endocrine organ. I recently heard that fat had a metabolic function, but I did not know that it was therefore classified as an organ. This is a relatively recent discovery in the scientific world, and will provide new hypotheses for years to come.
In our last class, on Monday, September 8th, we discussed a short article titled, "The Inflammation Age" from Better Nutrition. At the end of this article, it suggested that a simple blood plasma test that investigated levels of CRP (C-reactive protein) was the best tool to understand your risks of inflammation. However, Zoe pointed out to the class that the method may be skewed. Why do many of the articles given to us about obesity/diabetes and the relationship with diabetes suggests that levels of CRP can be an efficient way of detecting inflammation? After further investigation, I gathered that abnormal CRP levels can be the consequence of different things, such as viral infections and liver failure. Therefore, this test proves to not be very specific. As Zoe mentioned, this test may not accurately detect what we are looking for.
In addition to the above, I would like to pose a question for the future. What do you think is the most efficient way to treat obesity and diabetes? There have been multiple medications that have been tested and used. Exercise and diet have been tried countless times. Different surgical methods have been discovered and performed. I think that since all of the treatments have various routes, diverse side effects and risks, and distinct goals, it is very hard to compare them. Maybe each patient has a "best" treatment for themselves and their condition.
10 September 2008
A Clinical Application for Immunology
In class this Tuesday, we spoke briefly about immunological assays and how they have become widely used in the clinical world. Because I recently worked in a clinical lab using these techniques, I thought I would share the large part that they actually played.
Before coming to UCD, I worked for a clinical lab that concentrated on organ transplantation. When most people think of immunology and organ transplants, we think of anti-rejection drugs and antibody cross-matching (such as blood typing). As a part of the Infectious Disease department, our job was to make sure that organ donors did not have any infectious diseases (such as HIV and Hepatitis). It may not be inherently obvious as with cross-matching, but immunology plays an important role in this process. To do this, we used a process called Enzyme Immunoassays, or EIAs. This process is basically an antibody-antigen reaction.
When testing for these infectious diseases, the easiest, fastest, and most generally reliable method is to look in the blood for the antibody. A manufactured protein, similar in structure to the disease antigen is affixed to the bottom of a plate. When the serum or plasma of a patient is added, after a period of incubation, any antibody present in the patient’s blood will become bound to the antigen. Everything else is washed away, leaving only the antibody-antigen complex. This complex can be conjugated to a color development reagent, allowing visible representation of the amount of antibody in the blood.
This method of testing is very fast and efficient. If needed to be done quickly, all of the tests required by the FDA for whole organ transplantation can be done within six hours. (This is very handy for someone on a list waiting for an organ.) It is also possible to perform this kind of test on multiple patients at one time, as they can be done on 96-well plates. Unfortunately, some down-sides become apparent with this method of testing. For one, it relies on antibodies made to viruses, instead of the actual virus. There is a period time called the “window period” in which the virus is in the body, but our immune system has not been able to make a detectable amount of antibody. It is rare, but possible that an organ donor could have died without knowing they had recently contracted a disease, and their blood was drawn for testing during this window period. A solution for this is a method of Nucleic Acid Testing (NAT) called Transcription Mediated Amplification which detects the genetic material of viruses using a technique similar to PCR. This can detect the presence of a virus much earlier than EIA testing, but is not available for all infectious diseases.
Another drawback to using EIAs to detect diseases is the phenomenon of cross-reaction, which we also discussed in class. As you might imagine, there are proteins that are similar in structure to antibodies. Cross reactivity is one of the main causes of false positive results in EIAs. For example, if a blood sample is hemolyzed (the red blood cells have lysed), the protein fragments released could become bound to the antigen and the patient would appear to be reactive. There is not much that can be done about this, especially if a person has a medical condition that causes them to produce proteins similar to the antigen being tested for. As more nucleic acid testing becomes available, it will be easier to detect diseases, and fewer organs will have to be discarded because of false positive results.
If anyone happens to comment on this or have a question, I'll be out of town for the rest of the month :)
Before coming to UCD, I worked for a clinical lab that concentrated on organ transplantation. When most people think of immunology and organ transplants, we think of anti-rejection drugs and antibody cross-matching (such as blood typing). As a part of the Infectious Disease department, our job was to make sure that organ donors did not have any infectious diseases (such as HIV and Hepatitis). It may not be inherently obvious as with cross-matching, but immunology plays an important role in this process. To do this, we used a process called Enzyme Immunoassays, or EIAs. This process is basically an antibody-antigen reaction.
When testing for these infectious diseases, the easiest, fastest, and most generally reliable method is to look in the blood for the antibody. A manufactured protein, similar in structure to the disease antigen is affixed to the bottom of a plate. When the serum or plasma of a patient is added, after a period of incubation, any antibody present in the patient’s blood will become bound to the antigen. Everything else is washed away, leaving only the antibody-antigen complex. This complex can be conjugated to a color development reagent, allowing visible representation of the amount of antibody in the blood.
This method of testing is very fast and efficient. If needed to be done quickly, all of the tests required by the FDA for whole organ transplantation can be done within six hours. (This is very handy for someone on a list waiting for an organ.) It is also possible to perform this kind of test on multiple patients at one time, as they can be done on 96-well plates. Unfortunately, some down-sides become apparent with this method of testing. For one, it relies on antibodies made to viruses, instead of the actual virus. There is a period time called the “window period” in which the virus is in the body, but our immune system has not been able to make a detectable amount of antibody. It is rare, but possible that an organ donor could have died without knowing they had recently contracted a disease, and their blood was drawn for testing during this window period. A solution for this is a method of Nucleic Acid Testing (NAT) called Transcription Mediated Amplification which detects the genetic material of viruses using a technique similar to PCR. This can detect the presence of a virus much earlier than EIA testing, but is not available for all infectious diseases.
Another drawback to using EIAs to detect diseases is the phenomenon of cross-reaction, which we also discussed in class. As you might imagine, there are proteins that are similar in structure to antibodies. Cross reactivity is one of the main causes of false positive results in EIAs. For example, if a blood sample is hemolyzed (the red blood cells have lysed), the protein fragments released could become bound to the antigen and the patient would appear to be reactive. There is not much that can be done about this, especially if a person has a medical condition that causes them to produce proteins similar to the antigen being tested for. As more nucleic acid testing becomes available, it will be easier to detect diseases, and fewer organs will have to be discarded because of false positive results.
If anyone happens to comment on this or have a question, I'll be out of town for the rest of the month :)
28 August 2008
Antiphospholipid antibodies in children
I'm going to break the ice here and make the first student post because class this week got me all excited! Just this past week the lab I work in submitted an abstract about antiphospholipid antibody syndrome (APS) in children. In short, this syndrome is characterized by blood clots associated with so-called “antiphospholipid antibodies” (although, these antibodies generally don’t bind phospholipid, but rather phospholipid-binding proteins…for an excellent, in depth review see:
http://www.ncbi.nlm.nih.gov/pubmed/12871358?ordinalpos=27&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum ).
To be diagnosed with APS a person must present with a thrombosis (blood clot). They then need to have positive tests for antiphospholipid antibodies on two separate occasions that are at least three months apart. So, by definition, the people with APS consistently have these antiphospholipid antibodies, which are not usually present in normal, healthy people.
These so-called “antiphospholipid antibodies” are not necessarily directed against phospholipids - that is just the term that has been given to the population of antibodies that seem to be common in people with APS. For our discussion, it isn’t essential to understand what the antibodies are directed against because how each antibody may activate blood clotting isn’t entirely understood. For our purposes, all that needs to be understood is that these patients have abnormally high levels of autoantibody for long periods of time. This is true even when these APS patients are compared to other children who have had blood clots.
Our study focused on children who were diagnosed with APS. APS is a rather complex syndrome that is fairly common in adults with thrombosis but has been little studied in children. Our lab (which includes fellow classmates ChrisB7630 and MeghanC7630) started studying APS in children in hopes of finding a relationship between certain antiphospholipid antibodies and thrombotic outcome, with the long-term goal of using this data to improve clinical care for children affected with APS. Our findings (as presented in our abstract which follows in a comment - beware, it is quite technical!) found that, in general, children who have persistently positive (positive for at least three months) IgM antibodies are more likely to have had recurrent blood clots. After class we started to wonder if maybe the high levels of IgM themselves are responsible for recurrence, as high concentrations the big IgM molecules could make the blood "sticky". Or maybe having consistently high IgM levels is indicative of some sort of underlying inflammation that may have a role in thrombosis.
I’m very much looking forward to this class! I’m excited to see what light others can shine on our work. Yay!
Do bugs control your immune response?
We are multicellular creatures (metazoans) with about 30 million million cells. Each cell lives in its own tiny microenvironment which is slightly different from all others; no two cells are identical in position, function, or future. All cells depend for survival on interactions with their neighbors, mediated either by direct contacts or through soluble molecules like chemokines and cytokines, growth and survival factors. This makes me think that all instances of damage or infection that stimulate the innate immune system will be different, too. If it’s an RNA virus, for example, or an E. coli, the array of Pattern-Recognition Receptors that are stimulated will be different, and the soup of chemokines and cytokines made by affected cells will therefore be different, too, though they probably overlap. So no two innate responses will be exactly the same. Different individuals’ genetic makeup will also play a role. Now, we know that the link between the innate and the adaptive (antibodies, T cells) immune responses are the dendritic cells. They ingest fragments of the invaders and, influenced to mature and differentiate by the local chemokine and cytokine soup, leave the inflammatory site and travel to the lymph nodes, where they show their burden of antigen to the adaptive immune system’s T cells for evaluation and response. What I want to suggest is that no two arriving dendritic cells will be exactly alike, as they matured in different microenvironments. Thus they may stimulate the T cells which contact them differently, and this could result eventually in very different kinds of immune responses. For example, in one case the response may be mostly antibody, and in another, mostly T cell-mediated, as in Poison Ivy. Is it possible some pathogens have learned how to manipulate the immune system so that the response against them is ineffective? I’m thinking about HIV: everybody who is infected makes antibody to the virus, but it isn’t protective. T cell responses would be protective, the way they are to other viruses, but against HIV they are very weak.
11 August 2008
Welcome!!
Hello from sunny and HOT Tucson AZ.
PSIO 495/595K welcomes everybody to Inflammablog2!!
My name is Zoe Cohen and I'm the instructor of PSIO 495/595K.
I wanted to give everybody a little insight into our course. We are a colloquium, which means that we read many different articles (lay articles, basic science and review articles) related to Inflammation and Disease. We do not cover all of Immunology in this course! In fact, what you'll find is that the majority of posts from our class will similar for 2 weeks at a time. This is because we will discuss a specific disease (and how inflammation plays a role) for 2 weeks at a time.
Please post comments to my class if you find any of our topics interesting! We really enjoy getting the input of a graduate course (495k is undergraduate)!
If you'd like to see a copy of our syllabus, Dr. J. John Cohen has one that he can
show you!!Here's to a great semester!!
Zoe (or ZoeC495)
30 July 2008
Welcome to Inflammablog 2!
Welcome Brave Bloggers from IMMU 7630! I guess by now you have figured out that there are 2 courses sharing this Blog. The rules are different; in IMMU 7630 we blog about anything we want, and whenever we want; in PSIO 495 they have assigned topics and dates to blog. We will try to get that info for people in Colorado, as it makes things easier to follow. Everyone is invited to blog and to comment, ask questions, give more info, and so on. If you are cutting and pasting something from elsewhere, remember you must attribute it to avoid plagiarism.
Oh, try to keep your Titles short, there is a GoogleGlitch with long ones.
JJ
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