This is the beginning of a few posts that I am attempting to put together to break down the FPIES processes, from how I see it through research on FPIES studies, Non-IgE food allergies as well as digestion and immune system responses.
My disclaimer that this is FPIES specific, there are dozens (ok hundreds, millions?) of processes that can happen in the immune system and GI that may share mediators with FPIES; for example (and for simplicity?), I will not be going into everything a Tcell is responsible for- but how it (theortically) affects FPIES kids.
Terms & Definitions:
Antigen: Foreign substance that will produce an immune response.
Oral Tolerance: Specific supression and balance of the immune system towards an antigen.
Lymph nodes: Act as traps, or filters, for the immune system. Antigens are presented via the lypmph nodes.
Peripheral blood mononuclear cells: Lympocyte, monocyte, macrophage. Critical piece of the immune system to fight invaders. Lymphoctes are: T cells, B Cells and NK cells.
T-cell Lymphocytes: White Blood Cell's called the control cells (gatekeepers), classified according to markers on their surface (T-cell receptors- TCR). (T stands for Thymus, which is where they are regulated). Each Tcell has a specific receptor for each antigen.
T memory: cells to store the memory of the molecule the body classified as an antigen. Numbers quickly expand upon reintroduction of antigen.
T Regulatory cells (Treg)- Tcell lymphocytes involved in preventing intestinal inflammation, and regulating oral tolerance. Receptors can be either alpha/beta or gamma/delta, each receptor is responsible for recognizing foreign antigens and designating either induction or suppression.
T cells are classifed into 2 subsets:
CD8- (suppressor) monitor for antigens in the body to destroy.
CD4- (helper) responsible for cell and antibody mediated immune responses.
Subset of CD4 are T-helper (Th) cells:
1.Th1- cell mediated responses, regulation of defenses against bacteria, virusus, fungi, parasites. This process involves dendritic cells presenting the antigen to the Tcell and the T cell releasing cytokines which leads to the inflammation from recruited leukocytes to the site.
2. Th2 - Involves B-cells, and promotes antibody production (IgE allergy).
3. Th3=responsible for immune regulation of Th1/Th2, which gives us oral tolerance.
4.Th17- more recently discovered found in the lining of the GI tract and skin, responsible for clearing out fungi and bacteria (gut flora) with inflammation.
Each Th cells produces different cytokines involved in the immune responses.
Cytokines: Inflammatory mediators, responsible for the interaction and communication between cells that trigger inflammation and respond to infections. These include interleukins, lymphokines, tumor necrosis factor and the interferons.
Tumor Necrosis Factor (TNF): pro-inflammatory cytokine that induces death (necrosis) through the inflammatory process (controls responses by inflammation). Inflammation can be a protective measure- but it needs regulating (or you have auto-immune disorder of the body attacking itself).
Transforming Growth Factor (TGF-B1): Anti-inflammatory cytokine, a regulator of homeostasis of inflammation in immune responses.
Gut Associated Lymphoid Tissue (GALT): Digestive tract is equipped with it's own unique immune system. It consists of: tonsils, adenoids, Peyer's patches, lymphoid tissues, lamina propria. Everything taken in via the oral route is processed here for either rejection or tolerance of the immune system.
Peyer’s Patches: facilitate the generation of an immune response within the mucosa.
Lamina propria: connective tissue coating on intestinal lining (between surface cells and membranes of intestinal lining), part of the mucous membranes of the GI tract.
Toll-like receptor (TLR): receptors that recognize molecules from microbes that come in through skin and intestine and activate immune responses.
Dectin 1 agonist: works with Toll-like receptors in recognizing microbes.
Non-IgE food allergy (NFA): cell mediated response to food antigens.
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