Re: where is our immune system's 'memory' stored?

These are two excellent questions. Let’s deal with the second question first and define memory. The first response to an antigen, called a primary response, usually takes some time to develop. The antibodies produced are mainly IgM, the amount produced is small, and they are usually “low affinity”, meaning that they don’t bind the antigen so well.

The second time the same antigen is encountered, the response is much more vigorous – it is quicker, more antibodies are made, mainly IgG or IgA, and they bind the antigen better; they have high affinity. This is the memory response. To answer your question, our immune system’s memory is stored in cells, the memory B and T lymphocytes. I will stick here to the memory B lymphocytes, the ones that give rise to antibody producing plasma cells. In primary response, the frequency of cells able to recognize a foreign antigen is low, about 1/100,000 and when stimulated by antigen the produce IgM plasma cells. These two things account for the features of the primary response, slow and low quantities of IgM antibody. During the primary response though, other things are happening: 1) The antigen-specific B cells divide so there are a lot more of them to respond the next time they encounter antigen, and they can respond more quickly. They also will live a very long time. 2) The cells undergo “isotype switching”, which means that now they will make IgG or IgA antibodies. 3) The cells mutate their antibody genes so that now they bind antigen better. These changes account for the features of the secondary response, quick, lots of IgG or IgA antibody that binds antigen very well.

The first part of your question, how does our immune system discriminate between native cells and foreign cells, has intrigued immunologists for many years. It is sometimes called “self, non-self discrimination” and “self-tolerance”. One important mechanism has to do with how B lymphocytes react to antigen encounter at different stages in their life history. You make lots of new B cells every day in your bone marrow and each one has a different receptor for antigen. Some of these receptors will recognize your own cells and proteins and might cause autoimmune disease if not gotten rid of. Fortunately for us, B cells die if they encounter their antigen soon after they are made. As the B cells leave the bone marrow and go to other places like your spleen, tonsils and lymph nodes they change and become “mature”. Now if they see antigen they can respond and make antibody.