Immune responses to vaccines: adaptive immunity

I love summer! I love riding my bike when it's hot. More than that, I love riding my bike with Andrew in tow. Andrew and I recently rode out the Foothills Trail between Orting and South Prairie. We found a little picnic area next to a pond where we feasted on peanut butter sandwiches and homemade cookies and then sat together watching frogs, tadpoles, and dragonflies.

My garden seems to love the hot weather too. I spend most of my weekends working in my garden while neglecting this blog.

One of my reasons to discussing the different types of immune responses to vaccines is to use this as a basis for discussing different types of vaccines, why some vaccines are much more effective than others, why some vaccines require "booster" doses and others do not, and why some vaccines contain adjuvants.

In my last post I gave an overview of innate immunity; skin, mucous membranes, and stomach acid that act as barriers to foreign invaders, complement that tears holes in cells that are not recognized as self, and white blood cells that kill infected cells and others that eat pathogens. Although the goal of immunization is to stimulate adaptive immune responses, antigen-presenting cells, which are part of innate immunity, are integral to adaptive immunity.

Antibodies

Adaptive immunity develops after the immune system encounters a foreign antigen – something that is non-self. One of the most important parts of adaptive immunity is antibodies. As we saw in The Fantastic Voyage, antibodies attach to foreign invaders. Specifically, antibodies attach to antigens. Each antibody attaches to a specific antigen. By attaching to antigens on the surface of a pathogen, the antibody can block the pathogen from attaching to its target cell and prevent it from killing or invading that cell. Antibodies can also help phagocytic white blood cells engulf and destroy a pathogen. For example, a number of pathogenic bacteria are covered with a polysaccharide capsule – they are literally sugar-coated – which protect them from phagocytosis. Antibodies can attach to polysaccharide epitopes, giving the phagocytic cell something to grab onto.

NIAID/Jeanne Kelly

 

Think of antibodies as keys that fit locks. Each antibody fits a specific antigen. Sometimes the lock is similar enough to another one that a key that wasn't made for it will fit. Antibodies that fit an antigen other than the one it was made for are known as cross-reactive antibodies. Cross-reactive antibodies are beneficial when they attach to pathogens other than the one it was originally made to fit. Cross-reactive antibodies can also be detrimental when they attach to self-antigens, which is what happens in autoimmune diseases.

B-lymphocytes

B-lymphocytes, also known as B-cells, are the workhorse of adaptive immunity. B-cells transform into plasma cells and manufacture antibodies. The surface of B-cells is covered with B-cell receptors (BCR). These are essentially antibodies that are anchored to the cell membrane. Each B-cell receptor is made to attach to a specific non-self antigen, which is known as its cognate antigen; the antigen it "recognizes." Of course, a B-cell cannot see if its cognate antigen is actually attached to a pathogen, so it needs more information before it commits to cloning itself to make enough plasma cells to fight off an attack. One way is when there are many B-cell receptors on the surface of the B-cell engaged with many cognate antigens on the surface of a pathogen. Another is when there is a chemical messenger from other cells that tells the B-cell that there is a battle going on and its antibodies are needed. Sometimes B-cells need some help.

T-lymphocytes

There are a lot of different types of T-cells. For this discussion, I'm just going to talk about helper T-cells. Helper T-cells interact with B-cells in several different ways. A B-cell can enlist the help of a T-cell to determine whether it needs to differentiate into a plasma cell and make antibodies. T-cells can help B-cells make antibodies that are a better fit for the target antigen and they also help with immune memory. Helper T-cells also act as intermediaries between antigen-presenting cells and B-cells; an antigen-presenting cell brings the antigen to a helper T-cell that then attaches to a B-cell to "teach" it to make antibodies to that antigen.

While B-cells "recognize" many different types of molecules, helper T-cells only recognize protein antigens. That means that antibody responses to antigens that are not proteins, like polysaccharides, are T-cell independent; the antibodies do not "fit" as well as those made during T-cell dependent responses and immune memory is not as robust – it takes the immune system longer to remember that it has previously fought a battle with the pathogen and it takes longer to mount an antibody response than with T-cell dependent responses.

Incidentally, the human immunodeficiency virus (HIV) kills helper T-cells. Symptoms of acquired immunodeficiency syndrome (AIDS) appear when there are not enough helper T-cells to fight off opportunistic infections.

Cell-mediated immunity

Helper T-cells that have been activated by antigen-presenting cells can "teach" other types of white blood cells to recognize and kill infected cells. Cell-mediated immunity is one of the reasons live virus vaccines are highly effective.

Again, this is a simple explanation of very complex processes that I plan to use as a basis for discussions on a number of vaccines.

Thanks to all of my readers for 20,000 pageviews!

 

 

 

References

Kroger, A. T., Pickering, L. K., Wharton, M., Mawle, A., Hinman, A. R., & Orenstein, W. A. (2015). Immunization. In J. E. Bennett, R. Dolin, & M. J. Blaser (Eds.) Mandell, Douglas, and Bennett's principles and practice of infectious diseases, 8th ed. [Electronic version]. Saunders.

Pickering, L. K & Orenstein, W. O. (2012). Active immunization. In S. S. Long, L. K. Pickering, & C. G. Prober (Eds.) Principles and practice of pediatric infectious diseases, 4th ed. [Electronic version]. Elsevier.

Playfair, J. H. L., & Chain, B. M. (2005). Immunology at a glance, 8th ed. Malden, MA: Blackwell Science.

Siegrist, C-A. (2013). Vaccine immunology. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds.) Vaccines, 6th ed. [Electronic version]. Saunders

Sompayrac, L. (2003) How the immune system works, 2nd ed. Malden, MA: Blackwell Science.