The MHC is thought to be the most dense region of genes and most polymorphic region of genes in the human genome. It is highly unlikely that your MHC genes match any of your friends!! Tissue matching in this gene region is important in transplantation medicine and that is why this gene complex was originally called the histocompatibility complex. However, of all the millions of different allele combinations which could occur, each individual only expresses a small subset of all the alleles. Because the MHC presents antigens to the immune system, this means that we all "see" antigens slightly differently from one another and it is why we are more or less susceptible to some diseases and syndromes compared to others.
According to the published literature this is a conundrum for evolution or any origin model of the MHC. Consider this statement in a recent publication:
"An adaptive immune response is usually initiated only if a major histocompatibility complex (MHC) molecule presents pathogen-derived peptides to T-cells. Every MHC molecule can present only peptides that match its peptide-binding groove. Thus, it seems advantageous for an individual to express many different MHC molecules to be able to resist many different pathogens. However, although MHC genes are the most polymorphic genes of vertebrates, each individual has only a very small subset of the diversity at the population level. This is an evolutionary paradox."
Since we have also been exploring teleological explanations for the immune system, what might a teleogical view be regarding the MHC? What design advantage does the MHC provide?
Please share your thoughts with the group in this blog.
DUE Dec 10
This specificity of the MHC complex and the diversity among the encoding of the complexes could be necessary to accommodate different genders and their need for various MHC complexes. Male and females differ in their hormone production and the levels of individual hormones that are produced. Certain hormones are better supported by certain MHC classes. If these MHC molecules are reduced, disrupted, or are improper for the gender, then the balance of hormones and proper physiological functions could be detrimentally impacted. This demonstrates design in the fact that MHC classes will be expressed differently based upon gender in order to maintain proper hormone function. It also shows that the specificity of MHC complexes was purposefully designed in order to maintain gender differentiation and their proper physiological functions. The MHC complex is also said to be associated with the different odors in males and females. It has also been noted that individuals are attracted to the odor produced by the MHC that is opposite of their own. As a result of this, men and women are attracted to their opposite based upon scents. This shows God’s design to maintain the proper relationship between a man and a woman. This also supports the notion that these diversity in these MHC complexes was intended to maintain gender differentiation. This specificity of the MHC complex and the diversity among the encoding of the complexes could be necessary to accommodate different genders and their need for various MHC complexes. Male and females differ in their hormone production and the levels of individual hormones that are produced. Certain hormones are better supported by certain MHC classes. If these MHC molecules are reduced, disrupted, or are improper for the gender, then the balance of hormones and proper physiological functions could be detrimentally impacted. This demonstrates design in the fact that MHC classes will be expressed differently based upon gender in order to maintain proper hormone function. It also shows that the specificity of MHC complexes was purposefully designed in order to maintain gender differentiation and their proper physiological functions. The MHC complex is also said to be associated with the different odors in males and females. It has also been noted that individuals are attracted to the odor produced by the MHC that is opposite of their own. As a result of this, men and women are attracted to their opposite based upon scents. This shows God’s design to maintain the proper relationship between a man and a woman. This also supports the notion that these diversity in these MHC complexes was intended to maintain gender differentiation.
ReplyDeleteIt is possible the MHC is only contained in a small subset because too many would have caused too much variation. Since the MHC is involved in the immune system too much variation could perhaps cause autoimmune problems. From a teleological standpoint, this could be why they were designed to be contained in a small sub-set in the body. Since the varying MHCs that humans have affect the way they respond to antigens, this could also be a way to regulate infection and disease. If we all responded to the same antigens in the same ways it is possible that epidemics could be spread faster because the odds of having the same MHCs would go up as more MHCs were added. Also, if we were designed with the same MHCs this could also increase the risk of epidemic. Regulation of disease also points to creation rather than random chance.
ReplyDeleteSome studies have also shown that sexual preference is related to MHC. This is linked to olfactory response as smells will be given off and perceived differently depending on the MHC of a person. It has been shown in studies that animals as well as humans will prefer mates of dissimilar MHC. This is thought to be detected through olfaction. While this may seem like evolution on the surface, to me it seems like a feature designed to keep the pool of MHC variable and decrease spread of disease and other problems.
The MHC complex stimulates a T cell response by the immune system to attack foreign objects that are presenting different proteins. Maybe the MHC is almost another type of back up system to present the pathogens that have "gotten through" our first defense systems. And because we each are made a little differently, certain pathogens have a better chance of getting through which are the different alleles that are presented on the MHC. Each person is susceptible to different pathogens at various levels because of their immune system. Maybe because the MHC is like a back up system, the alleles presented on it are for the pathogens that we are susceptible the most to. Because if the pathogen did not get destroyed and got into our cells, we start feeling sick before the antigen is presented on the MHC. God created the MHC as another system to help prevent us from succumbing to the many different types of pathogens in the world.
ReplyDeleteI like your point on how MHC can perhaps be a back up system to present the pathogens that have slipped away from the first defense system. I also see MHC to be specific in that since every person is susceptible to different pathogens at various levels because of their immune system, that person's MHC has to present alleles that are for the pathogens that they are susceptible the most to. It is also specific in that it has to make a certain protein to allow the interaction with the antigen fragment, which will be presented to the T cell receptor. The MHC is a design feature because only God knows the state of our immune system, and the needed alleles one needs in order to fight off pathogens that we are susceptible the most to.
DeleteIt seems clear from looking at the wide variety of coping mechanisms in place in the natural world that variability is a life-sustaining trait. The various ways in which organisms defend themselves or derive sustenance from their surroundings all vary and change with their different environments. The MHC complex is no different, as its role in immune defense is one of the most important functions the immune system is required to carry out to fight an infection of any kind. This mechanism needs to be as variable and flexible as possible in order to relate to the millions of pathogens that our body will fight off over our lifetime. However, the role that this variability plays over our entire species points to a safe-guard for the human race. If mankind as a species contains very similar MHC regions, then we will all be similarly susceptible to certain antigens over others. This lays all of humanity open and vulnerable to a pathogen that can slip past the few MHC variations mankind possesses and wipe us out. For us to possess many different kinds of MHC coding regions as a species allows for certainty that no pathogen will be encountered that can pose a serious wide-spread threat to humanity. The MHC complex is ensured to work and function well even when exposed to unforeseen pathogens.
ReplyDeleteIt is much less clear why each of us as individuals do not possess the great variability of the MHC that the rest of human possesses as a whole. However, the function of the MHC indicates that if our bodies were able to synthesize a dizzying array of different kinds of MHC complexes, our T cells would have to be equally as varied and complex to be able to interact with them, and our entire immune system would be to be many orders of magnitude more complex than it already is. Such increases in complexity would end up proving to be wasted energy and would probably make us more susceptible to the many pathogens that we encounter on a regular basis and are not "exotic". Our immune system is fine-tuned to respond extremely well to the common offenders on the pathogen list, and so keeping things simple as regards the MHC complex will undoubtedly allow us as single organisms to respond readily and efficiently to the most prevalent dangers.
I think Janelle makes a good point in that the MHC could have a "back up" characteristic. Because of the vast majority of combinations these variable regions possess, these MHC's are able to recognize and protect the body from harmful invaders. The human population is estimated to have 12 million different combinations for HLA 1: A, B, and C. The variability region of the MHC is probably the most important in terms of producing a proper immune response because without the ability of the MHC to be flexible and variable it cant stimulate a proper response. T cell activation solely depends on these MHC's being able to recognize and present antigens for T cell receptors. The vast number of MHC diversity permits greater diversity of antigen presentation. Shannon makes a great point in that if we all responded the same way to an antigen there would be ways, I think, for pathogens to escape this type of response to clear the immune system. But since there is such variability there are different ways to combat one pathogen, by using different HLA's to recognize it. Pathogens technically would not be able "to keep up" with our ability to recognize them because there is such vast variability.
ReplyDeleteReading about how MHC's play a role in mate selection does seem like an evolutionary model but I think Tori is right in that it can be seen with a design point of view in that opposite sexes are attracted to each other on even a genetic level. That even down to the genes of an individual, God had perfected a plan and made us to be with the opposite gender.
ReplyDeleteWith what has been discovered with the MHC complexity and variability, it would make sense for our immune system to not be able to possess all combinations because that would add to even more complexity of the T cell receptors. That would seem to be "messy" and not needed. One characteristic that stands out is that a few different molecules are able to display a high variety of peptides. We do not need that "much complexity." But we have a few molecules that are able to take care of a variety of pathogens.
I think that all of you have brought up extremely valid points. The MHC is clearly involved in mate selection. It protects human kind from all being wiped out by one disease. But what i think is the most interesting part of all of this is how God uses microevolution as a tool. The MHC develops the way it does because different people are exposed to different antigens depending on their environment. This is definitely microevolution, but it was used by God to protect humans from being completely wiped out. Part of me wonders if it also might have been caused by the fall of the Tower of Babel, though of course i have no proof. It would just be interesting to see if God used the MHC to seperate us and protect us at the same time. For instance, people from different countries have immunity to their own native diseases, which is why we have to get so many shots when we travel somewhere. So God has divided us both by language and disease. But at the same time, He protects us through our diversity because this way we can't just be wiped out by one disease. It is truly a blessing and a curse.
ReplyDeleteThe MHC being used as an attractant might be an evolutionary tool as well. People and animals are attracted to other people and animals that have dissimilar MHCs. Their offspring would then also have a very different MHC. This way MHCs continually change and become more diverse. It's just another way the GOd can use any means He wants to achieve His purpose.
After reading about the characteristics and functions of the MHC, I can’t conclude that MHC can be explained through evolution; but instead, see the MHC as design feature. Also learning more about the MHC, God’s grace is displayed in the design of the MHC. I see the MHC in a design perspective because it is highly polymorphic. Every person has different forms of MHC proteins that are presented, and this variation aids in the prevention of a widespread epidemic. I agree with Shannon’s view on “if we all responded to the same antigens in the same ways, it is possible that epidemics could be spread faster”. One of the characteristics of pathogens is being able to mutate quickly, such as HIV. If everyone had the same MHC proteins, a pathogen can mutate in order to avoid being presented by MHC proteins, and the entire population would be susceptible to the pathogen. Also as Shannon stated, MHCs were designed to be contained in a small sub-set in the body. Being designed to contain small sub-sets in the body is purposeful, in order to prevent autoimmune problems. That is the reason why the immune system rejects transplanted organs many times due to too much variation in the MHC genotypes of the organ donor and the acceptor. I think that if God did not design the MHC to be polymorphic and designed to be contained in a small sub-set in the body, pathogens will easily evade the immune system, and we will be very easily sick.
ReplyDeleteOne possible advantage for the MHC in its design is that it reduces the possibility of autoimmune disorders. If the MHC had increased numbers of alleles, it’s possible that it would recognize its own proteins and attack itself.
ReplyDeleteAllowing for teleological differences is wise from a design standpoint because it increases the survivability of the population as a whole. If everyone responded the same way to every antigen, then a single antigen could wipe out the entire human population. Since humans respond differently to different antigens, some humans will be able to survive different antigens that maybe other humans would not.
Studies have shown that the MHC is involved in sexual mate selection. This has the potential to create diversity amongst populations, as those with certain MHC alleles will be attracted to those with different MHC alleles. Other studies indicate that there are lower rates of early pregnancy loss in human couples of different MHC genes. MHC phenotype is involved in how humans perceive odor of compounds from sweat, indicating how the MHC may contribute to mate selection. God has designed the MHC to increase diversity in the human population and thus decrease the spread of disease and illness.
Honestly, that’s a pretty good question. I’m not too sure why the individual is not able to express all of the millions of combinations of MHC. It may be for the purpose of efficiency or something along the secondary response time. If the each individual body contains ALL of the possible alleles and genes and codes for every possible pathogen, it might be an excessive amount of memory floating around in our body. That would be similar to having a 10,000-page dictionary, which would contain probably every word ever said but it would take much more time to sort through and find. If every MHC has a specific t-helper memory cell floating around waiting for a secondary response, we would have an unnecessary amount of cells floating around in our body, and in this may actually end up “crowding” resulting in making other critical processes inefficient.
ReplyDeleteThe design advantage of the MHC, specifically not having the same set as every other person, is variability. If we all had the same set of DNA, same weaknesses, same strengths and vulnerabilities then it would only take one disease/virus to wipe out the earth. However, by having different subsets humans as a whole has more flexibility and a greater chance of adaption. It seems that our personal differences in immunity are a weakness on the individual level, but as a “whole” these differences and weakness are what gives us strength.