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 or dis-advantages involved in using a mutation system to increase immune function in this way?
Due Nov 20
The mutation process has at least a few distinct advantages as a design. First of all, if the antibodies were not generated by mutations, there would have to be a gene for each of the different antibodies. DNA is already packed into the nucleus; it would be even more difficult to package the DNA if there were so many genes. Through mutations, all of the antibodies can come from fewer genes. In this way, mutations consolidate the genetic material within the nucleus. Generally, mutations are harmful because they are not regulated. Most mutations happen spontaneously or are caused by error in transcription or translation. This is not the case with somatic hypermutation. It is carefully regulated by a system that is built into the genes. In fact, somatic hypermutation is much more like recombination in germ cells than any mutation in somatic cells. The main purpose of recombination is also to generate great variability from small amounts of DNA.
ReplyDeleteAnother advantage to mutations is that they allow the body to adapt. Pathogens have not stayed the same throughout history, but have constantly adapted. Mutations make it possible for the immune system to adapt just as swiftly (if not swifter) than the immunogens themselves. If the human race just stayed static and stuck to the same 1,000,000 antibodies, pathogens would quickly adapt to survive those specific antibodies. We would be dead before we knew what hit us.
The only problem I can see with using mutative system would be if you had too much variability and you started killing off the good bacteria in your system, or even your own cells. Perhaps this is how some autoimmune diseases develop. God was gracious in setting up a system that creates exactly the right balance of variability in our bodies.
You made a good point in pointing out how the DNA can be packed more tightly in the nucleus and how that can be beneficial.
DeleteFrom a design perspective, a mutation would be used to increase antibody diversity and affinity because it shows that possibly the antigens were created for some other purpose than to cause harmful disease and so there must be a mutation that will fight off this other mutation because of the Fall. Sarah brings up a very good point that unless mutations were used for antibodies, there would have to be a gene for every type of antibody which would be an enormous amount that would change the entire structure of a nucleus and eventually a cell. Using mutations as a means of increasing the number and kinds of antibodies allows the body to adapt and be able to fight off a new type of antigen. If the genes to create antibodies can mutate into something new, when a new type of virus or bacteria is presented in the body, the body can maybe mutate a previous antibody code into a new one that would be able to fight off the new attacker. I am sure there are thousands of new types of bacteria and viruses that are mutating every day around the world. If we were "stuck" with the genes that we had, our bodies would not be able to fight many of these foreign objects. The hypermutation method of increasing antibody affinity and diversity is not a harmful type of mutation because it changes something for the better that will protect the body more successfully.
ReplyDeleteUsing the mutation process to increase antibody diversity and affinity has its advantages. Mutations in the binding sites of antibodies give them an enhanced ability to recognize and bind to antigens. This is especially helpful since bacteria and viruses are continually mutating. These antibody mutations can also increase antibody diversity. Sometimes it may be advantageous to have just one antibody with high affinity, while in other instances it may help to have several antibodies with varying degrees of antibody affinity. Increasing affinity with a low dose of antigen causes the antigen to bind to the highest affinity antibody first, meaning B-cells will produce more of these high affinity antibodies than those antibodies with reduced affinity. The mutation process provides for a variety of antibody affinities. Another advantage is that the cells don’t actually have to code for these mutations because they are random. The cell undergoes random mutations that are not highly controlled by the cell, and thus does not use energy on regulating and specifically coding for these changes as it does in other processes.
ReplyDeleteA disadvantage to this system would be that these mutations would not always result in effective antibodies. Some mutations would make worse antibodies and would be a disadvantage to the body in fighting infection. Another disadvantage is that with the mutation method, you cannot control what changes you make to antibodies. The mutations cannot be directed by the body because they are random.
could your last paragraph about ineffective antibodies have anything to do with autoimmune diseases maybe? If a mutation makes a wrong antibody that instead is coded to attack your own cells instead of a foreign object. hmmm. idk :)
DeleteYou made a good point on cells not using energy on regulating when undergoing random mutation, because the cells do not have to code due to mutation being random. Is this perhaps the reason why viruses and pathogens live longer because they also do not use energy when mutating?
DeleteFrom a design perspective, mutation provides a efficiency and extreme diversity to the immune system. Mutations occur in the hyper-variable region, specifically the CDR, and this allows the cell to mutate the sites directly responsible for antigen recognition. As we have seen in class, mutations allow an enormous potential of antibodies to be made to combat the constantly changing and new antigens that enter the body. Antibody that are successful in binding, become stored in the memory and hence second exposure affinity is greater. By having an adaptive process like this, it eliminates the need to store ALL the billions of gene combinations and reduces it to only those which are effective or necessary. Reducing the total pool size of antibody stored in the memory must increase the efficiency of creating proper Ig and also response time. Somatic hyper-mutations also give immune systems the ability to adapt to mutating strains of virus and pathogens. It would seem that hyper-mutations could also be dangerous in the way they cause down-syndrome and other diseases, however somatic hypermutations function more similarly to a gene shuffler. The mutations which occur are specific for individual cells and are not passed transferred to new cells, which may prevent the permanent expression of a disadvantageous gene combination.
ReplyDeleteThe mutation process is beneficial because it allows the body to make millions of different antibodies. Not only that, but it allows the body to make these different antibodies without having to have a specific gene for each one. There is a certain set of genes that can be mutated to create the desired result. Also, mutations do not just occur in somatic hypermutation. They also occur in viruses and bacteria and other pathogens. Since viruses and bacteria have the ability to mutate, somatic hypermuatation makes it possible to make antibodies for viruses that may not have been present in years past. This gives the immune system the ability to adapt to whatever is thrown its way. Also, the ability to increase affinity is beneficial because having a lose dose of antigen causes the highest affinity antibodies to bind first leading to the production of more high affinity antibodies and less low affinity antibodies.
ReplyDeleteA disadvantage to this system is that there is always a chance of detrimental mutations occurring. These could cause problems in the cell or allow an antigen to proliferate within the body because of a mistake in the mutated antibody. It is also possible that the antibody does not have a mistake but is just too low affinity and is not effective. Also, too much variability could possibly result in the death of beneficial bacteria in the body which could cause a host of problems within the body.
From a creationist perspective somatic hypermutation is beneficial for the human genome because it allows the human body to fend off various kinds of pathogens. Somatic hypermutation allows for controlled mutations among the genes that code for antibodies. This is done by making substitutions in variable regions of the genes that code for immunoglobulins. By allowing for controlled mutations the human genome is permitted to have fewer amounts of immunoglobulin genes, while also having the ability to produce various amounts antibodies. Another benefit to hypermutation is its ability to adapt rapidly to viruses, bacteria, or pathogens that have mutated. Since viruses, bacteria, and pathogens continue to mutate and develop mechanisms to evade the immune system, SHM is necessary in order to keep up with and defend against these mutated invaders. Lastly, the ability of the B cell’s produced to increase affinity is extremely beneficial because those produced with the greatest affinity will generate a sufficient memory cells and plasma cells. As a result of this, the plasma cells will produce affinity specified antibodies that will produce antibodies to that specific antigen. Then the more the body encounters that the higher the affinity the antibodies will have for it. As a result of this, the body becomes more proficient at removing that particular invader.
ReplyDeleteThe only problem I could see with this system is the fact that some mutations could be detrimental. The system could either make a substitution in a variable region that would inhibit the production of antibodies. This in turn would allow the pathogen to infect at a greater and more detrimental rate. The system could also make a mutation that would generate antibodies that possess a low affinity and are not effective on the present antigen.
1. Why use a mutation process to increase antibody diversity and affinity?
ReplyDeleteThis mutation process is beneficial for increasing antibody diversity for the purpose of increasing its ability to adapt to many different (or mutated) antigens. There does not have to be one gene for one specific antibody. One gene can code for many antibodies with this mutation process. This creates a greater line of defense against pathogens. The ability for antibodies to be mutated helps them "keep up" with all the different foreign invaders that mutate as well. The immune system daily is in this process continually fighting off invaders. This process of somatic hypermutation is restricted to B cells, which aids in the increase in affinity because the B cells produced that have a high affinity to an antigen will produce more B cells with that high affinity. Memory cells and plasma cells will produce antibodies with that specific affinity. So each time the body comes into contact with that antigen, the higher affinity it will have toward that antigen. It becomes a process, like Tori said, where the body becomes more and more efficient in removing foreign pathogens.
2. What are some of the advantages or dis-advantages involved in using a mutation system to increase immune function in this way?
ReplyDeleteAdvantages would include the ability to have a diverse amount of antibodies with a lower amount of genes. As stated earlier the body has the ability to code for 10 billion different antibodies when the body only has 20,000+ genes. Mutation is an advantage for the body to be more efficient in removing unwanted foreign invaders.
The one main disadvantage I see with mutation and that is common in this topic is that antibodies aren't mutated "correctly" or that they are mutated and can cause harm instead of good in binding to foreign antigen. The pathogen could have a greater chance at infecting the host with a mutation gone wrong.
The mutation process by which an antibody's affinity increases over time is an interesting and highly complex aspect to a seemingly straightforward correlation between pathogen recognition and immediate response through antibody production. The ability the immune system utilizes to allow gradual mutations to the pathogen binding region on an antibody without allowing deleterious breakdown of the antibody's other structures is an ability that creates a gradually higher-performance antibody weapon against repeat sightings of a specific pathogen. There are several advantages to this system, and a few drawbacks alongside.
ReplyDeleteFirst of all, why is mutation specifically used to carry out this increasing affinity aspect to the antibody defense system? It is clear that the genetic code involved in antibody assembly is highly specific and pre-determined early on in B-cell differentiation. This means that once an antibody is developed in response to an epitope recognition, that antibody generation is locked-in and finalized. Other than altering the Ig isotype by changing the heavy chain region, that binding site is final. Perhaps a perfect match was not attained upon the first epitope recognition process. Mutation allows for an antibody generating process to react gradually to slight changes in pathogen epitopes, and to perhaps remedy an otherwise irreversible mistake made at the first genetic recombination required to begin antibody synthesis.
Advantages are fairly easy to discern in this mutation system. Mistakes made in the APC recognition process can be reversed, and gradual mutations that occur in pathogen epitopes over time can be mirrored in the antibody production process without requiring a whole new cloned cell family. It can also be beneficial that by design, affinity increases gradually over the antibody cell line's lifetime. If there were somehow a cross-reaction whereby an antibody was produced that could interact both with pathogen cells and host compounds, the tissues would need time to adjust and limit the immune response to certain regions in which cross-reacting was better localized. If affinity for these binding zones started out at an absolute maximum value, the self-damage involved would be crippling from the very beginning.
Disadvantages are clear: when a pathogen enters a host tissue-it is best for all antibodies produced in response to be as high in affinity for the epitope binding zones as possible so that the immune system can have a better and faster response to infection. It is also clear that this mutation process whereby affinity is developed is a very slow and drawn-out process that occurs over many decades of an organism's life. This mutation process is not one with any kind of real impact in regards to immediate infectious and dangerous immune crises. In the end, however, it is clear that this complex and often-overlooked development process in the immune defense mechanism has the potential to assist an organism as the aging process occurs and as other tissues become weaker and less coordinated. A stronger immune system will only increase an organism's survival rate at advanced age, and that is exactly what this mutation-driven antibody development cycle does.
I find increasing of antibody diversity and affinity through mutation to be purposeful when knowing that viruses and bacteria mutate continually. If mutation increases antibody diversity, mutation is beneficial because having diverse antibodies can more easily fight against mutated invaders. Furthermore, increase in antibody affinity will result in the binding of antigen to the higher affinity antibody first. And as a result of antigen binding to the higher affinity antibody first, these higher affinity antibody will be produce more by the B cell than the lower affinity antibodies.
ReplyDeleteA disadvantage of using a mutation system is that since mutation increases antibody diversity, too much diversity may result in an antibody being useless in its purpose. Also another disadvantage is that, since there is no coding necessary in this mutation process because they are random, it is hard for the body to regulate these mutated antibodies.