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So I get the concept that a vaccine is a weakened form of a virus so that the body can "learn" to fight it and make a person immune to that disease, but how exactly does this learning take place? What learns? The white blood cells? Do they have their own database or something and do they go from cell to cell informing them of what they learned? I read that they only last around 5 to 7 days so that means there's constantly new white blood cells that also need this information for all diseases ever encountered. How does this work? Thanks!

CodeMonkey
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So while some kind of a biological database might have been an evolutionary option, the way we evolved is different from this. Rather than 'planning' what diseases could be recognized in the environment and recording this, our bone marrow constantly pumps out naive B and T cells that have a randomized receptor on them. The effect of this is that every new B and T cell that your bone marrow makes will recognize a unique, random protein sequence, and you will have billions of these cells floating around in your blood circulation at any given time. These cells however will only float around in circulation for a short period of time before dying and being replaced by other cells with new random sequence receptors.

When you get a vaccination, you are injecting in specific protein sequences from a specific pathogen. As these injected protein sequences circulate through your blood they will eventually bump into a B or T cell that has a receptor that recognizes them. When this happens, the B or T cell will now start to divide and give rise to long lasting memory cells that express the exact same receptor and will therefore recognize the exact same protein sequence again in the future. These cells will float around in your blood for most of your life and make you 'immune' to the recognized pathogen. When you get reinfected with the same pathogen or the pathogen to which you were vaccinated these memory cells will rapidly divide upon recognition of the pathogen and give rise to a large number of effector cells that eliminate the pathogen before it can 'make you sick'.

What is really cool about this is that because each T or B cell carries on it a receptor that recognizes a random protein sequence, you currently have in you B and T cells that would recognize a protein that does not even exist on Earth, but might exist on Mars or somewhere else in the Universe. This makes our immune system quite valuable because any protein that nature creates for all of time anywhere in the universe will still be recognizable by our immune systems.

The Nightman
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  • Thanks for the answer! Can you clarify how the memory remains if the B and T cells only last for a short while and would then be replaced by randomized ones from the bone marrow? I presume they must reproduce as well, but if they're reproducing while the marrow is making random ones, wouldn't the population be hard to manage? – CodeMonkey Mar 03 '15 at 20:50
  • So the recognition remains because of specific cells called memory B and T cells. These are almost identical to all of the naive short lived B and T cells but they last for most of your lifetime if not all of your lifetime. So they do not need to reproduce until you get reinfected with the pathogen. So typically these memory cells will be present in low numbers and just wait in the blood for 80 years, and then every time you get exposed to the pathogen they recognize they rapidly produce millions of new cells with the identical receptor to eliminate the pathogen. Make sense? – The Nightman Mar 03 '15 at 20:58
  • Ahh, so the "naive" B and T cells are short-lived, but if they come into contact with a protein befitting them they will create a "memory" B or T cell and those permanently remain? – CodeMonkey Mar 03 '15 at 21:01
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    Correct. The idea is that if a naive cell doesn't come into contact with and recognize a protein within a short while then it might not recognize a pathogen in your environment (or a protein sequence that even exists for that matter) and is eliminated so your blood doesn't just become a sludge full of too many cells. But when a naive cell does come into contact with and recognizes a protein it will produce a small population of memory cells that are very long lived so that they will be able to rapidly respond the next time you come into contact with the pathogen. – The Nightman Mar 03 '15 at 21:05
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    The B/T cell receptor is not only recognizing proteins, it is recognizing antigens in general. Most of these are proteins, but they don't have necessarily to be proteins. – Chris Mar 03 '15 at 21:11
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    There is also a subsystem to eliminate B cells that recognize "self" (which includes food). Obviously it's not good for the immune system to go after "self" molecules. And that's exactly what does happen in auto-immune diseases: the "identify self" subsystem glitches. – dmm Mar 03 '15 at 22:02
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    Right, I think a really good answer should cover clonal deletion and affinity maturation. The first explains why you aren't immune to "self" and the second is an important part element in making the polymorphic immune system even better. – Francis Davey Mar 03 '15 at 22:35
  • Basically the adaptive immunity responds to shapes of the antigen, rather than sequence. – One Face Mar 04 '15 at 00:44
  • This is all also very relevant information. It's true that antigen recognition is far more complex that just the amino acid sequence of a protein. And yes many other compounds can show positive binding to the TCR/BCR especially some carbohydrates and lipids, though in those of these cases recognition is not straight forward, and other proteins must be available for this to occur. – The Nightman Mar 04 '15 at 00:54
  • As for the shape of the antigen determining binding to the TCR/BCR. In a sense this is correct in that the 'shape' of the receptor fits the 'shape' of the antigen, but to those without an in-depth biochemistry background this may be a bit misleading, because you could make an identically shaped molecule with vastly different charge distribution that would have no reactivity to the receptor. So because of this I find it easier to just explain it as the amino acid sequence determining binding. But all good points. – The Nightman Mar 04 '15 at 00:54
  • Recognition by peptide sequence applies much more to TCRs than antibodies. – canadianer Mar 04 '15 at 01:08
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    If this is the case, how do some vaccines last longer than others? – Cat Mar 04 '15 at 02:42
  • @canadianer TCRs are structurally similar to immunoglobulin. AFAIK TCR recognize the shape of the peptide presented by the Antigen Presenting Cells. Am I wrong? The point about charge never occurred to me, although now thinking retrospectively it is obvious! – One Face Mar 04 '15 at 07:45
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    @Eric that would be an excellent question to ask separately – One Face Mar 04 '15 at 08:00
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    @CRags All receptors recognize shape insofar as it is defined by the spatial arrangement of atoms and electron distribution in a molecule. TCRs recognize short peptides that are proteolytically generated from larger proteins and presented on MHC. Although some local folding is expected, the peptides are pretty linear and are not in the native configuration found in the original protein. That is what I meant by recognizing peptide sequences. A BCR recognizes amino acids by their arrangement in the tertiary structure without any requirement for them being close in the primary sequence. – canadianer Mar 04 '15 at 08:17
  • @Eric, some vaccines last longer due to mutations of the disease. The flu, for example, is different every year so the previous vaccination does very little for the new strain. I can only guess Tetanus must also mutate then but at a much slower rate or something. I'm not the biologist though so as CRags indicated, it's a good question to ask separately :-) – CodeMonkey Mar 04 '15 at 16:27
  • Afaik. TCR binds only to MHC1, so it won't recognize what you inject in a vaccine. Most of the vaccines are B cell vaccines. Creating T cell vaccines is much harder and it is bleeding edge science. – inf3rno Apr 29 '15 at 23:33