Somatic hypermutation is an amazing process which increases the diversity of the antibody response and can also lead to an increase in antibody affinity over time. As we noted in lecture, the human body has the potential to make 10 billion different antibodies from just a few gene regions and somatic hypermutation helps increase this diversity.
Somatic hypermutation is a process which essentially involves specific but semi-random mutation events which are focused only on a small region of the antibody genes. The small region just happens to be the binding site of antibodies for foreign antigens.
Mutations at large in the genome are often deleterious, yet somatic hypermutation and a process of selection leads to positive benefit for the host. Thus, from a design perspective we cannot say that all mutations or natural selection processes are neutral or bad or deleterious.
But from a design perspective, why use a mutation process to increase antibody diversity and affinity?
What are some of the advantages involved in using a mutation system to increase immune function in this way?
Due Dec 1
Using a mutation process to increase antibody diversity and affinity allows for flexibility to combat the ever changing pathogen community. This mutation process allows the human body to cope with the changing attackers and address them properly. If this was not the case, bacteria or--even more dangerously--viruses, would change beyond the parameters of the human immune system (the Ab diversity and affinity) and would easily ravage through the human population. That is what causes a epidemic/pandemic. The flexibility built in (by God) allows the body to adjust to these changing dangers and be able to defend against them.
ReplyDeleteWhat I am trying to understand is if this mutation process plays any role in the rejection/attack of foreign matter. Would antibody diversity and affinity matter when it comes to the defense against foreign tissues/particles/chemicals/objects?
If I am understanding your question correctly, I would think that the diversity caused by the mutation process would matter in the defense against foreign tissues/particles/chemicals because, with the production of 10 billion differing antibodies, there is a greater chance that the antibodies would have a genetic sequence with some degree of affinity that would tag the object as an antigen.
DeleteSome advantages involved in using a mutation system to increase immune function include faster response times of immune response in following exposures to pathogens, very specified molecules that can more effectively target the pathogens. So essentially, these mutations allow for faster and more effective responses. This is essential because it helps to protect the human body against large scale pathogenic attacks/exposure, as well as small scale long term attacks/exposure. Also, one of the greatest benefits is the ability for vaccination, and for single vaccinations to protect against multiple like-structure pathogens.
ReplyDeleteOne thing that I am wondering is if this mutation system is the aspect of the immune system that allows the body to recognize “self” or if they are unrelated. Thoughts?
Hey Kyle, interesting question. I did a little research into what determines self-recognition within the immunological realm. It turns out that somatic hypermutation does not really have much to do with self-recognition. This phenomenon is caused by T cell receptors (TCR) differentiating between foreign and native antigens, which are presented by antigen presenting cells. (APCs). Thus, while the hypermutation we’ve been discussing is not inherently related to the idea of self-recognition, the mutation is what occurs directly after the TCR-APC complex identifies a foreign antigen.
DeleteA mutation process actually makes a lot of sense to me. In the human genome SNPs (single nucleotide polymorphisms) occur frequently. This is a good thing because these SNPs, seemingly irrelevant, play a very significant role in the differentiation of DNA sequences per person. This contributes to the great diversity we see amongst individuals as 99% of the human genome is the same. Therefore, it makes sense to me that in order to create diversity in the realm of antibodies, mutations would be a great way to do that since this makes the options limitless for the DNA sequences. A huge advantage to utilizing a mutation system, I would think, would actually make it easier on the genetic sequence. If the there was a specific gene coding for every single type of antibody that the human body makes, that would take up a magnificent amount of space on the genome to encode 10 billion different antibodies in addition to all the other types of proteins. Another advantage to utilizing a mutation process is because pathogens can experience microevolution. This is seen with bacterial infections that can adapt to antibiotics creating superbacteria. The mutation process creating such a wide diversity of antibodies gives an individual a greater advantage of being able to combat such pathogens.
ReplyDeleteI think you made a good point with the bacterial infections adapting to antibiotics. If bacteria are able to mutate and microevolve to survive, I think it it makes sense for our cells to act similarly. It is a good thing that the somatic hypermutation only effects one generation of cells and that their new traits are not passed on to other cells. I am not sure how much good this would actually do, or if it would effect the rest of the system. If too many cells changed that may cause more confusion for the immune system, rather the system brilliantly changes a few cells then processes the rest normally.
DeleteAs Kyle and Whitney have already explained, the somatic hypermutation can beneficial to the immune system because it allows for adaptability. The body is constantly fighting against different enemies all day everyday. Our cells must combat different bacteria, viruses, and antigen; they therefore must be able to adapt to change in these foreign enemies. Somatic hypermutation allows for this adaptability by changing immunoglobulin specificity. With a change in specificity, antibodies and other immune cells can properly and effectively protect the body against foreign agents.
ReplyDeleteAlso, somatic hypermutation not only increase antibody affinity towards an antigen but can decrease it as well. This can be important if there is ever an auto-immune issue in the body.
All of this maybe grace by God. In the garden, there may not have been as much of a need for hyper mutation but not there certainly is. Or perhaps, the mutations our bodies endure were actually used for different reasons pre-fall. Hypermutation may have been beneficial in a different way, not as much as a protective defense but maybe a tool to do something else.
Tim, you bring up an interesting point. To postulate further on your question, I wonder if Adam and Eve were created with an active immune system. We can agree that disease and infection is part of the curse, thus necessitating immunological protection. However, pre-Fall, was the immune system simply dormant or was it simply never activated by antigens? This said, I would assume that even in the Garden, humans had the somatic hypermutation ability to make antibodies, they just never contacted an antigen.
DeleteCampbell, I think I would agree with you partly here. I think the body came into contact with these antigens, I just think that there was no immunological response to them. God created everything after 6 days and it was good. This would involved helpful bacteria that could have eventually mutated and become pathogenic. Disease and infection are a part of the curse; however, I think all of the opportunity for disease and infection were present pre-fall, but our bodies never responded to it. The only way to tell whether or not something is pathogenic is to see if we have an immune response to it. There could be many other pathogens present in the world right now that our bodies don't recognize as such because we don't have the proper Ab receptors to it. So to answer your question with another question, could the immune system be active but not be able to recognize pathogens? Or does an active immune system directly imply that we react to certain antigens/pathogens? Because if this is the case, then I would venture to say that Adam and Eve's immune systems were inactive.
DeleteI want to add my thought to that as well. Mutation is not always good. Bad mutation such as the multiple heads, limbs, and so on, which allow these organisms to live for a short period of time. What is the purpose of this harmful mutation? Why would God allow this to happen? Or maybe only after the-fall that this was presented.
DeleteThe somatic hypermutation found within the genome, as mentioned by everyone who posted before me, allows for greater variance and diversity when coding for antibodies. However, continuing along with Whitney’s point, this type of mutation also allows for a higher efficiency, as it conserves space by mixing and matching the different regions. Thus, the genome we have in our immune cells has the ability to rearrange itself through mutations in order to isolate the highest affinity antibody for a given antigen, and it does this with a very limited number of gene regions. It is the multitude of combinations that gives rise to such a plethora of antibodies.
ReplyDeleteSomatic hypermutation gives rise to a constantly adaption that could not be emulated apart from a massive scale DNA sequence. As mentioned in the blog introduction, our body produces ten billion different antibodies, all of which are created through this mutation. Furthermore, somatic hypermutation gives rise to selection of high-affinity antibodies. Upon contact with antigens, the cell codes for the antibody with the highest affinity for the antigen. Thus, somatic hypermutation is both efficient (in size and material) as well as effective (ability to produce high-affinity antibodies).
Why mutation? God never gives us more than we could take, I can apply this verse in this problem in term of how God would not allow all those genetic diseases, varies sickness, and all type of bacteria/superbugs, etc, if He doesn’t have something else for us to use against these. The reason why using mutation process to increase antibody diversity is because it provides a much variety of different antibodies against many diseases that could possibly present. As have mentioned by Whitney some advantages of mutation, she made her point on how mutation helps limit space among genome in encoding antibodies as well as the variety of antibodies against varies bacteria. Space always seems to be a very important factor in all type of reactions. Certain structure of molecule, enzyme, and the reaction needs to be in a specific distance, length, position and affinity as well as structure to make the reaction possible. Other advantage might include the decreasing of antibodies affinity which can be helpful in cure auto immune response disease while increase affinity of antibodies can help fight against varies types antigen.
ReplyDeleteAs some of my classmates have already pointed out, mutations in our genome can be very helpful, as it allows for fewer genetic storage of information and allows our bodies to adapt more efficiently to changing microbes and pathogens. As Dr. Francis mentioned in his original post, large mutations in our genome more often than not wreak havoc, so why choose mutation as a process by which to create something good? I think the answer lies in our Sovereign God. Ultimately, His ways are high above our ways, and we could never understand how and why the Lord does things (Isaiah 55:8-9). But in trying to understand God's purposes, we can better understand the world around us. I think that in a way, God may be saying that even things that seem to be meant for destruction, He uses for good. He controls all things, and He causes all things for our good and His glory, even if it doesn't seem like it at the time. Even those genetic mutations that cause some of the most horrible diseases and illnesses, are still good because they are sovereignly directed by God. I am so glad that His ways are higher than mine!
ReplyDeleteI think your totally right Shannon; we can all come up with reasons as to why things work the way they do, as we have. But ultimately, the reason why every is here is the first place and is continually functioning is because the Lord has it be that way. God could have chosen any other way to diversify antibodies, but He chose somatic hypermutation. As we dive deeper into the specifics of immunology and really any realm of study, we can’t help but acknowledge the greatness of our God and the depravity of man. Of course this can be taken too far in that we use God’s infinite knowledge and wisdom as an excuse to not study the world around us. Claiming that it is likely too much for us to understand, which is probably true. Thankfully we haven’t done that, the world around us is a direct reflection of God as He is the creator of all things. By studying the world, we gain a better understanding of who God is.
DeleteMany mutations do indeed have small or negative effects, but the ones that control genes can have major (and sometimes positive) effects. Within the human body, the effects are good! Our immune system has the unique genetic mechanism that enables it to generate an almost unlimited number of different light and heavy chains by joining separate gene segments together before they are transcribed. This allows us to use B cells to generate a diverse pool of antibodies from relatively few antibody genes. Our bodies now have a great way to defend against a variety of different antigens using a limited amount of antibodies to begin with.
ReplyDeleteOnce again, we can discuss the soverignty of God, even from the beginning of creation. Antigens pre-Fall most likely did not affect the body the same way they do now. Our body pre-Fall did not have to combat diseases and foreign pathogens. But, God knew the Fall would occur and that things created for good would decay. He built in our bodies and our gene mechanisms a way that we could combat a multitude of antigens with an originally limited amount of antibodies. He gave our immune systems the flexibility they need to adapt, even in the form of mutations. He causes all things fo His good and glory, even things that were meant for evil.
ReplyDeleteSomatic hypermutation allows the immune to properly respond when facing a new pathogen. Like others have already pointed out, without the diversity that results from hypermutation, the body would not be able to efficiently combat the ever-changing pathogens that we come across every day. As Whitney stated, the mutation allows the body to be able to operate on a relatively low number of genes. If there were one gene for each antibody, then human genome would need to be much larger in order to accommodate that.
ReplyDeleteThis design feature allows for greater affinity because each antibody is now tailor made for each pathogen. This allows for compartmentalization of the immune system due to the fact that each antibody will bind to a specific foreign substance. Without this specificity, the body would activate immune responses that are likely not necessary for the given issue. The human body cannot afford to always be participating I these immune responses. The mutations’ development of specific antibodies not only prevents the unnecessary activation of the immune system, but will also increase the rate at which is responds. Upon exposure to the foreign substance, memory cells will be generated in preparation for the second exposure. There will be antibodies on standby ready to be used if needed. Upon activation, B cells will then be signaled to begin to generate more of the needed antibodies. This specific signaling is only possible if there is a system in place that distinguishes the 10 billion antibodies. This system has been put in place by God; He understood the necessity for an immune system that is able to adapt to the changing pathogens we will be exposed to.
The mutation systems to increase immune function are favorable in making antibodies in many different ways. Antibodies are required to be different and very diverse in order to be able to attack antigens from foreign bodies. The only way we can do this is through the diversity in antibodies, which is mostly created by mutations that can oppose the diversity of infectious foreign bodies that our body could face. Another way that mutations are very helpful in is that they keep the genome small. Therefore mutations permit the cell to consume the smallest area with vey wide range of antibodies.
ReplyDelete