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Play the video to watch Professor Mathieu describe the overall picture in detail
What is the global picture? We believe that, in genetically predisposed individuals, you might have an initial assault on the beta cell. This could be, for instance, an increased metabolic demand or a virus, and will lead to the death of some beta cells. Antigens and other peptides and proteins from these beta cells will be released into the surrounding tissue and will be taken up by professional antigen-presenting cells, typically dendritic cells. These dendritic cells will process the antigens from the beta cells and present them, on their surface, in the presence of HLA proteins. And these HLA proteins will then present the beta cell peptides to other cells of the immune system, typically T lymphocytes. Now these dendritic cells draw in cells from the immune system – namely lymphocytes. They will start to secrete chemokines and cytokines that will attract lymphocytes and also activate them. These lymphocytes – typically CD4 T lymphocytes – will start to proliferate. And, normally, you have a balance between effector T lymphocytes and regulator T lymphocytes that will keep the whole system in check. But the effector T lymphocytes will also talk to other cells of the immune system. For instance, you will also get activation of B lymphocytes that will start making antibodies against the original peptides presented by the dendritic cells. Antibodies will appear in the blood of individuals that are destroying beta cells, so you will find antibodies against, for instance, insulin or GAD, in the blood of these individuals. But there is also communication with other cells, like with CD8 T lymphocytes or with monocytes that become macrophages. And eventually these monocytes that become macrophages will start to secrete, again, cytokines like IL-1, IL-6, TNF-alpha, that will create a whole inflammatory environment around the beta cell and that inflammatory environment will make the beta cell, again, more vulnerable to the rest of the immune attack. The other lymphocytes, the CD8 T lymphocytes, will also become activated and will then be able to directly destroy the beta cell through, for instance, perforin-activated mechanisms. Now, this circle, with the beta cell dying because of “innocent” reasons and then, eventually the beta cell being killed off by immune cells, is one all of us probably experience now and then. But it is only in genetically predisposed individuals, with, for instance, weaker beta cells or with an imbalance between the effector and the regulator cells that will eventually experience this circle over and over again, leading to the destruction of all the beta cells. Now, one final thing – the beta cell is not just a sitting duck being destroyed. It does something very specific. Namely, when it is attacked, when it is being exposed to inflammatory signals, for instance, it starts to secrete itself all kinds of products, like chemokines, that will draw in more cells of the immune system and, so, you have a vicious cycle happening. So, I invite you now to partake in our e-learning module and discuss with us the pathogenesis of type 1 diabetes.
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APC: antigen presenting cell
CD40L: CD40 ligand
CTLA-4: cytotoxic T lymphocyte antigen-4
Fas-L: Fas ligand
IFNa: interferon alpha
IFNy: interferon gamma
IL-1: interleukin 1
IL-12: interleukin 12
IP10: IFNg-inducible protein 10
MCP1: monocyte chemoattractant protein-1
MHC I: : major histocompatibility complex
ONOO-: peroxynitrite
TGFb: transforming growth factor beta
TNFa: tumour necrosis factor-alpha
Tc: cytotoxic T cell
Te: effector T cell
Tr: regulatory T cell

van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev. 2011 Jan;91(1):79-118