Physiology of Intestinal Immune Function Flashcards
WHY?
GI Tract is largest lymphoid organ in the body.
GI Sxs are common among immunodeficient patients.
Epithelium
Epithelial barrier
- Secretion of goblet cell mucus (bacterial prevention)
- Tight junction integrity (limits penetration of antigens)
- Production of cytokine-transforming growth factor beta: promotes tight junction integrity and maintains immune tolerance.
-Secretes chemokine: allows retention of B and T cell to “home in on epithelium.” Presents absorbed antigens to lymphocytes in a non-sensitizing manner
Epithelium
Abnormalities: bacterial functions, trigger production of cytokines (TNA-alpha, IFN-gamma)
Disease state: Epidermis bulls (impaired gut adhesion): causes intestinal inflammation
Plasma cells
- Most abundant type of lymphoid cell.
- Terminally differentiated B cells produce IgG.
- Majority produce IgA
- During inflammatory responses there is an increase in production of IgG and subtypes.
IgA
- Generated in response to gut flora and luminal antigens in gut wall lymph nodes
- Intestinal lymph nodes important in regulating intestinal tolerance mechanisms
- Secreted IgA transported through epithelium to gut lumen: adheres to bacteria. Decreases trans cellular absorption of antigen. Secreted IgE accelerates enterocyte antigen uptake.
Dendritic Cells: Antigen uptake ad presentation to T cells
- Sampling of dietary and bacterial antigens.
- Cluster in organized lymphoid follicles (Peyer’s patches)
- Localized between enterocytes to sample luminal fluid
- Samples antigens attached to IgA or IgE antibodies
Paneth Cells and M cells
Paneth Cells: produce antibacterial peptides. alpha-defensing production: adjusts bacterial flora. indirectly regulates T cell response.
M Cells: specialized epithelial cells of the follicle associated epithelium of the GI tract. M cells believed to act as an antigen sampling system.
Macrophages
Effector cells that produce large # of mediators when activated (TNA-alpha, IL-1beta). Kill ingested bacterial. Neutralize viruses. Newly recruited monocytes can increase the inflammatory response.
PNMs
Proinflammatory response to pathogens (infection or Crohn’s).
Eosinophils, Basophils, Mast Cells
Eosinophils normally present in stomach, SI and Colon (not in esophagus).
Overlap among all 3 cell types: TH2 immune response, Helminth infections. Less degree intestinal motility.
Upon activation: Eosinophils, Basophils, Mast Cells increase in inflammation. Produce cytokines and proinflammatory mediators. Increases vascular permeability. Promotes antigen penetration. Sometimes can interact with intestinal neural cells causing dysmotility and increased pain.
Chemokines
Chemokines are cytokines that exhibit the ability to attract leukocytes into sites of inflammation.
Produced by most intestinal epithelial cells.
Active participants of cell-mediated immunity and Th1 and Th2 responses
GALT: Gut associated lymphoid tissue: organized into 3 compartments
- Diffuse lymphoid tissue of intestinal lamina propria: Plasma cells (IgA), T lymphocytes (CD4+) T reg cells.
-Intraepithelial: intraepithelial lymphocytes (CD8+) MK cells which provide intestinal surveillance - Organized lymphoid follicles (TI Peyer’s patches): permeable M cells: allows penetration of both bacterial and dietary antigens: drains to mesenteric lymph nodes
-Appendix: dense lymphoid follicles important in mucosal immune priming
Intestinal Flora
Intestinal bacterial help create signals in the epithelium to induce production of T cells: via dendritic cells, Toll like receptors.
Also help to produce TGF-Beta. Develops IgA responses. Epithelial integrity.
Intestinal micronutrients
Regulatory T cells and intestinal epithelium dependent on Zinc, Vitamin A, Vitamin D
TH1 Responses
T cells that produce cytokines and activate macrophages which secrete potent pro inflammatory cytokines (TNFalpha) along with other radicals, mediators, and enzymes
