We are multicellular creatures (metazoans) with about 30 million million cells. Each cell lives in its own tiny microenvironment which is slightly different from all others; no two cells are identical in position, function, or future. All cells depend for survival on interactions with their neighbors, mediated either by direct contacts or through soluble molecules like chemokines and cytokines, growth and survival factors. This makes me think that all instances of damage or infection that stimulate the innate immune system will be different, too. If it’s an RNA virus, for example, or an E. coli, the array of Pattern-Recognition Receptors that are stimulated will be different, and the soup of chemokines and cytokines made by affected cells will therefore be different, too, though they probably overlap. So no two innate responses will be exactly the same. Different individuals’ genetic makeup will also play a role. Now, we know that the link between the innate and the adaptive (antibodies, T cells) immune responses are the dendritic cells. They ingest fragments of the invaders and, influenced to mature and differentiate by the local chemokine and cytokine soup, leave the inflammatory site and travel to the lymph nodes, where they show their burden of antigen to the adaptive immune system’s T cells for evaluation and response. What I want to suggest is that no two arriving dendritic cells will be exactly alike, as they matured in different microenvironments. Thus they may stimulate the T cells which contact them differently, and this could result eventually in very different kinds of immune responses. For example, in one case the response may be mostly antibody, and in another, mostly T cell-mediated, as in Poison Ivy. Is it possible some pathogens have learned how to manipulate the immune system so that the response against them is ineffective? I’m thinking about HIV: everybody who is infected makes antibody to the virus, but it isn’t protective. T cell responses would be protective, the way they are to other viruses, but against HIV they are very weak.
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If only the immune response to HIV were ineffective then if could be the antibodies. If antibodies are not all equal in their ability to fight off infection couldn't the antibodies generated in response to HIV just all be ineffective antibodies? Noone can produce one that is specific enough or the ones that are specific enough fail in another fundamental aspect. Like when they bind HIV the structure of the functional domain is compromised and no longer recognized by the rest of the immune system?
The mention of Poison Ivy in class sparked my memory of a story I heard on NPR a few weeks ago. Here is a link to the audio and/or transcript of the short piece on the radio:
http://www.npr.org/templates/story/story.php?storyId=93564476
No one is really sure why people with HIV fail to make a curative T cell response (as people with measles, say, do). In the vaccine trials, subjects made antibody but were not protected; unlike measles! As we'll discuss in class, HIV has a number of tricks for avoiding antibody.
That's an interesting article on poison ivy. It seems to be a myth that native Americans prevented poison ivy by eating the leaves.
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