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Inflammatory Bowel Disease (IBD) - Coggle Diagram
Inflammatory Bowel Disease (IBD)
General Information
Crohn disease
Ulcerative colitis
Genes associated
mutation in NOD2 (receptor for PAM and DAM recognition)
Bacteria cannot be recognices early, thus they stay in gut longer --> inflammation
after flare:
regeneration of epithelial cells
The mucosal immune system
effective barrier due to
intact intestinal epithelium, surface mucus secreted by goblet cell, normal peristalsis and secretion of protective factors (eg. antimicrobal proteins)
innate immue system
neutrophils, monocytes, dendritic cells, macrophages, NK-cells and innate lymphoid cells
express pattern recognition receptors thath bind stereotypic microbial products
epithelial, endothelial and stromal cells
adaptive immune system
B- and T-Lymphocytes
humoral immunity
mediated by B-cells in gut
secretion of ABs (largely IgA)
cellular immunity
mediated by T-Lymphocytes
CD4+ helper T-cells
respond to processed AG on APCs with MHC2
Th1
Th2
Th17
CD8+ (cytotoxic T-cells)
respond to processed AGs on all cell types with MHC1
regulatory T-cells (Treg)
Immune dysregulation and IBD
Dysregulation in epithelial barrier
upnormal Antigen presentation by epithelial cells and interaction with intraepithelial lymphocytes
handeling of unfolded intracellular proteins, process that is assiciatet with stress, is changed
Dysregulation in immune cells
Excessive immune cell recruitment and activation
encreased level of cytokines due to myeloid cells with inflammatory phenotype in lamina propria
NK cells subsetes are altered
T-cells show increased proliferation and cytokine production to antigens
abnormal B-cell regulation, increased number of B-cells, plasmacells, autoantibodies, and antibodies (IgA and IgG)
enhanced expression of adhesion molecules an leukocytes and entothelial cells, increased chemokines, increased leukocyte binding to endothelial cells
Dysregulation in secreted mediators
high secretion of IFN-gamma and TNF-alpha (proinflammatory)
extended infiltration of eosinophils contibutes to inflammation (due to secretion of IL-4, IL-5 and IL-13)
Key Concepts of the mucosal immune system
components must be properly balanced
layers of the intestinal immune system cooperate to defend
unique phenotypes of cells
Macrophages
more effective in clearing bacteria; anti-inflammatory characteristics;
produce less cytokines
less inflammatory and less activation
Intestinal dendritic cells
express high levels of retinoic acid-metobolizing enzimes
promote enriched T.cell trafficking to intestinal tissues and regulatory T-cell function
T-cells
more Tregs!
conditions in intestinal inveronment can influence the intestinal immune state
eg. inflammation, secreted mediators, microbiotica, dietary factors...
most of the action happens in peyers patches
Pathogenic vs common:
Therapie
make use of the plasticity of intestinal immunes cells
eg. Th17 can change to Il-10 producing Tregs and Th12 cells
bloxk mucosal homing of leukocytes
Antibody mediated therapies:targeting alpha-4 beta-7 integrin heterodimer, that is important for lymphocyte trafficking --> Natalizumab in Crohn disease
Vedolizumab in CD and UC
using anti-TNF-alpha antibodies for CD