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we know that all antigenic molecules don't have PRR on phagocytes and so they use an adjuvant that has a receptor for pattern recognation and fuse it with in order to phagocyte the antigen-adjuvant complex and present it on MHC II molecules for antibody syntheses now the question arises the phagocytes don't know which molecule is antigen and which is adjuvant then why MHC II molecules don't present the adjuvants for antibody syntheses and make the body sensitive against adjuvant and future vaccination should not be successful because the antibody recognises the adjuvant binds with it and not letting the vaccine to be processed?

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  • $\begingroup$ Some adjuvants are not immunogenic. See this article. $\endgroup$ – WYSIWYG Nov 6 '15 at 5:42
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Basically, this is what is happening when you receive a vaccine.

  1. Immunoglobulins are being made agains protein adjuvants such as flagellin
  2. Some of the adjuvants based on endotoxins such a lipopolysaccharides are not proteins. While there are some immunoglobulins produced that detect these molecules, the majority detect proteins
  3. Most antibodies are produced against the functional conformation of the protein, so its tertiary or quaternary structure. When polypeptides are loaded into MHC II, it is a small piece of the primary sequence of amino acids. This is used to activate CD4+ helper T-Cells.
  4. Vaccine is given in one of three ways; subcutaneously, intramuscularly, or orally (including nasally). Most antibodies circulate in the blood until they leak out of the blood vessels at the site of an infection. Also free antibody have half-lives of between 7 to 21 days, so even if there had been IgG in the tissue from a prior inoculation, it is unlikely that any will be at the site of the new inoculation without an inflammatory response taking place.

Oral vaccines will encounter IgA molecules in the mucus, so if they were made from a prior immunization, they could opsonize the vaccine, however, it is likely given in a high enough dose that some of the vaccine will reach the antigen presenting cells.

When delivered subcutaneously or intramuscularly, the vaccine will first be encountered by the innate immune system, even if adaptive immune cells were activated in previous rounds of vaccination. It is very unlikely that IgG will be encountered at the site of the inoculation, as IgG circulates in the blood and only ever really gets into the site of inoculation or infection after the innate immune cells have initiated an inflammatory response leading to the permeabilization of the blood vessels, allowing other immune cells and immunoproteins access to the site of the infection. Either way, APCs will be taking up the vaccine before the antibodies against them can neutralize them.

It is also likely a good thing that there are CD4+ cells in circulation that recognize a sequence of the adjuvant. If the B cell phagocytoses the vaccine and adjuvant, such as with a flagellin fusion vaccine, because there was specificity for an epitope on the target protein (vaccine), then even though the B cell is not making an antibody to the adjuvant, putting the adjuvant sequence on the MHC II means that it can be activated by a helper T-cell that recognized the adjuvant polypeptide, even if there is no T-cells that recognize the vaccine.

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    $\begingroup$ a lot of this is "common knowledge" for those of us familiar with vaccines an the immune response.. but can you list some sources? $\endgroup$ – Vance L Albaugh Dec 8 '15 at 5:36
  • $\begingroup$ @VanceLAlbaugh That is going to take me a while. The answer was written completely from memory and I did not refer to any sources when writing it. That being said, that knowledge is based on extensive study and reading on immunology. $\endgroup$ – AMR Dec 8 '15 at 7:48
  • $\begingroup$ A general source would be Janeway's Immunobiology, 8th Edition. But basically one would need to read the entire book and make the various connections to how the different systems play a role in the response to Pathogen Associated Molecular Patterns, Cytokines, Antigen presentation, etc. The answer is a summary of all of that information and how it is interconnected to one another. $\endgroup$ – AMR Dec 8 '15 at 7:56
  • $\begingroup$ @VanceLAlbaugh Are you okay with Janeway... This popped up again, and I don't know whether to work on it or just delete. Also WYSIWYG is right in that there are non-organic compounds used as adjuvants... $\endgroup$ – AMR Jan 7 '16 at 1:07
  • $\begingroup$ I'm completely fine with Janeway - he was a great immunologist and had a great book - used it in my graduate immunology course. I like your answer - a good compact explanation - nice work $\endgroup$ – Vance L Albaugh Jan 7 '16 at 2:07

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