But, Crohns is the immune system ramped up, right?
I don't believe so. There is a considerable amount of immunodeficiency in crohn's disease, crohn's disease involves innate immunodeficiencies. I don't know if it helps, I always wanted to test myself by writing it all down.
The immune system has 2 tasks. Immunological recognition (detection) and immune effector function (containment and elimination).
*Our first line of defense to invasion is the physical barrier and the release of certain types of proteins that are secreted, especially in the intestine.
If the invader actually manages to bypass those defenses, the innate and adaptive immune system come into play.
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innate immune system , a very old type of defense, almost all animals have a form of this immune system. It's an extremely fast response that happens within hours after infection. The main weapon of the innate immune system are white blood cells called phagocytes, particularly macrophages and neutrophils. They will literally ingest the invader and eliminate it. The macrophages and dendritic cells also produce signaling molecules, they come up a lot, they're called cytokine (one of them is
TNF-alpha). They signal other immune cells, and they can signal the brain to induce a fever to help kill bacteria, they help immune cells talk to each other. Macrophages are present all over the body, especially the intestine is lined up from top to bottom with inactive macrophages, ready to defend it. They live quite long compared to other white blood cells, they are matured monocytes. They are one of the key elements in crohn's disease.
--dendritic cells--
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The adaptive immune system, this is an extremely specific immune system that tends to take days to respond. Dendritic cells from the innate immune are the main link to the adaptive immune system. Dendritic cells (and to a much lesser degree, macrophages) set off the adaptive immune system. Dendritic perform what they call "antigen presentation", they are antigen presenting cells, APC, they present the invader to the adaptive immune system, and they do this by travelling to lymph nodes. The cells present this antigen to, extremely important cells,
lymphocytes. Specifically T cells. T cells constantly travel in lymphoid organs, they are called "naive T cells" when they're not active. Once they are activated, the effector T cells start travelling quickly to the tissue where the initial bacteria or infection is taking place, "lymphocte migration". CD4+ T cells help macrophages of the innate immune system kill microbes by activating them, and CD8+ T cells kill infected cells themselves.
There is another part of the adaptive immune response, and that's the humoral response, consisting of B lymphoctes. B lymphocytes recognise antigen and are most active against certain microbes and toxins. Helper T Cells can activate them and they expand extremely quickly, thousands per second. Many of those B cells then start to secrete "antibodies", those antibodies can "tag" certain microbes "opsonize" for phagocytosis.
Certain immune systems also have a "memory", the second time they encounter those invaders, they will respond much quicker than the days it took to activate the adaptive immune system.
Vaccinations exploit this by letting the body recognise certain types of infections.
I posted a picture of an APC in the Wiki forum once.
In crohn's disease, the innate immune response seems to have issues correctly recognising and eliminating those bacteria. NOD2 and ATG16L1 and many other gene mutations result in issues when macrophages try to eliminate these bacteria. Autophagy has been recently recongised to be very important to eliminate those bacteria. What people assume happens in crohn's disease is that the innate immune system is not capable of eliminating those bacteria, the adaptive immune system is activated by an APC, antigen presenting cell, T Cells are activated, those T Cells try to activate more macrophages, those same macrophages can not eliminate the macrobe, more APC arive in the lymph nodes, activating more T Cells, and you get a viscious circle of continuous immune activation. So the treatment in crohn's disease revolves around, controlling that immune response by immunosupression, and elimination of bacteria through antibiotics.
Another way is simply stimulating the innate immune system and autophagy...this would be the preferred solution...and people with crohn's disease actually already do this...this is why we take vitamin D or make sure out vitamin D is optimal, it appears that vitamin D stimulates autophagy through NOD2 and ATG16L1 and thereby helps us eliminate bacteria, partly correcting the innate immunodeficiencies. And studies looked at this, and I have linked this, and for example, vitamin D helps clear AIEC in crohn's disease, invasive E coli specific to crohn's disease.
So our immunse system is not "ramped up", it is more that we are "immunodeficient", specifically, we have innate immunodeficiencies, and our adaptive immune system is likely chronically stimulated.
Once you have that part down, you can easily start to understand crohn's disease studies that start to talk about those innate immunodeficiencies, it is often more specific, it is often called autophagy deficiency, or macrophage deficiency, commonly it is just referred to as innate immunodeficiency in crohn's disease. A lot more studies that seem very complex will start to make sense rather quickly, it only takes very limited knowledge about how the immune system works to start to understand what most studies trying to unravel the cause talk about.
It also becomes easy to understand why people are interested in bacteria like AIEC and MAP now...those bacteria are bacteria that are capable of exploiting those innate immunodeficiencies, in fact AIEC's main forte is exploiting autophagy weaknesses.
It's also easy now to understand why many researchers, much more so than GI, talk about diseases that have at first glance, little to do with crohn's disease. Diseases like HIV and chronic granulomatous disease. These diseases are important, because they involve specific immunodeficiencies, and they can teach us about crohn's disease, and what happens when an immune system is compromised. In HIV the immunodeficiency revolves around those T cells I mentioned, same thing with lymphopenia. In fact many people with crohn's disease have lymphopenia.
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That being that it is actually an under response to attack. 