Flashcards in Mucosal Immunity Deck (31):
What are the 3 traffic signals that bring immune cells to the gut??
alpha4beta7 and CCR9 - immune cells
MadCAM - endothelium
CCL25 - epithelium
What do mucosal dendritic cells produce from vitamin A?
Retinoic acid through expression of retinal dehydrogenases
What drives class switching to IgA in T-depending class switching in the gut?
How do T cells recognize antigens?
1st signal: T-cell receptor
2nd signal: co-stimulatory molecule (CD28) recognizes co-stimulatory receptor (CD80/86) on APC
How do B cells recognize antigens?
1st signal: membrane bound IgM
2nd signal: costimulation -- complement receptor, toll like receptor
How much IgA does the gut secrete per day?
A molecule that induces an immune response
A molecule that binds to (is recognized) by antibody (B cells) or T cells
A molecule that induces immune unresponsiveness to subsequent doses of the molecule
Specific unresponsiveness to an individuals SELF antigens
What does mucosally induced tolerance help to prevent?
Intestinal disorders -- food allergy, celiac disease, inflammatory bowel disease
What is the predominant T-cell mediated immune response in the gut?
What cell mediates the non-responsiveness to food and microbiota?
Regulatory T cells
How do mucosal dendritic cells regulate the induction of tolerance in the gut?
Gut DCs take up antigens from the gut (food or microbiota) travel to mesenteric lymph nodes and present Ag to T cells --> Cell produces retinoid acid and TGFbeta --> drives differentiation of CD4+ naive T cells to become regulatory T cells (FoxP3+)
What are the three things that contribute to autoimmunity?
Genetic susceptibility - susceptibility genes (HLA and non-HLA)
Environmental triggers - smoking
Uncontrolled immune response - hypersensitivity
What causes hypersensitivity?
1. dysregulated or uncontrolled response to foreign antigens resulting in tissue damage and injury
2. failure of self-tolerance followed by immune responses directed against "self" antigens (autoimmunity)
Mast cells and eosinophils, vasoactive amines, cytokines
Opsonization/phagocytosis, complement and Fc recruitment of leukocytes
IgM and IgG mediated
Complement and Fc recruitment of leukocytes
Mediated by Immune complexes
CD4: macrophage activation, inflammation
Mediated by T cells
What are some non-HLA genes that contribute to autoimmunity?
How might mutations in MHC contribute to autoimmune diseases?
Inefficient displaying of self-antigens
Poorly stimulated regulatory T cells
How are autoimmune diseases treated??
Systemic immune suppression
Non-systemic immune suppression -- Antibodies to TNF (Infliximab) and soluble TNFR (Etanercept)
Plasmapheresis or competitive FcR inhibition
Loss of oral tolerance to wheat (gluten)
Increased levels of de-aminated gliadin peptide
Associated HLA types with Celiac disease
HLA-DQ2 and HLA-DQ8
Why type of hypersensitivity is Celiac disease?
Type IV - Th1 cells and inflammatory response damage tissues
Loss of tolerance to microbiota
Inflammatory Bowel Disease
What mutations are associated with IBD?
Mutation sin Nod pattern recognition receptor gene
Mutations in autophagy (cellular homeostasis) genes
What HLA types are associated with IBD?
HLA-DR and HLA-B27
What type of hypersensitivity is IBD?
Type IV - Th1 (Crohn's) or Th2 (ulcerative colitis) --> inflammatory damage