Immunology of the GI System - Clarke Flashcards
What are the homeostatic relationships between lymphocyte populations in the Central Immune System vs. Surface Immune System?
- Central Immune System
- tendancy toward TH1
- complement mediation
- IgG, IgA1, IgA2, IgM
- Surface Immune System
- tendancy toward TH2
- agglutination antibodies
- mucosal Ab’s: IgA1, IgA2, IgE, IgM, IgG
What immune tissues participate in gut immunity?
- Intraepithelial Barrier
- Lamina propria
- Peyer’s Patch
- Mesenteric lymph nodes
What are the seven immune strategies employed to defend the host from invading pathogens?
- Block entry into the organism (most pathogens)
- Block entry into the cell (bacteria, viruses)
- Prohibit spreading (most pathogens)
- Direct killing (most pathogens)
- Kill infected host cell (virus, intracellular bacteria, protozoa)
- Expulsion (multicellular parasites)
- Nutrient deprivations (bacteria, protozoa)
What is the importance of immune tolerance in the gastrointestinal tract?
- Significant role to Treg cells to suppress inflammatory responses.
- Treg’s are an important contributor to immune tolerance
- Importance = lymphocytes may become hyperactive and amount immflammatory responses to previously tolerated particles
- imbalances of commensal bacteria may initiate aberrant inflammation
- e.g. Celiac disease, Crohn’s, Ulcerative colitis
What are the three parts of host defenses to parasites?
- Exterior barrier that relies predominately on cornified epithelia (Skin) to provide a wall to microbial invasion and utilizing IgE and IgG to label non-self material
- Interstitial spaces in the body utilizing IgM (circulatory only) and IgG (circulatory and interstitial spaces)
- Mucosal boundaries using fluids (saliva, tears, and mucous) to flush material and polymeric IgA to label non-self material.
What does the Intraepithelial Barrier refer to?
refers to the epithelium of the small intestine; site for effector T cells and expansion of memory/effector T cell populations
What is the lamina propria? Why is it important in the immunological status of the GI system?
- the connective tissue of the gut mucosal, restricted to stroma above the muscularis mucosae
- Reservoir to 70-80% total lymphocytes
What are the Peyer’s Patches?
- the inductive site for the mucosal immune system, site for B2 lymphocyte development , class switching and the production of secretory IgA
- note antigen is delivered by a specialized epithelial cell, M cells, to professional antigen presenting cells to prime naïve T cells
- there are no afferent lymphatic
What happens in the Mesenteric Lymph Nodes?
nodes receive afferent lymphatic drainage, site for B2 cell development and maturation of IgA, IgE and IgG producing plasma cells.
What is the primary site for antigen entry in the GI system?
Gut-Associated Lymphoid Tissue
What is αEβ7? Why is it important?
- member of the integrin family and is expressed almost exclusively by cells of the T lymphocyte lineage in mucosal tissues
- The chief ligand for αEβ7 is E-cadherin, an adhesion molecule (CAM) found on epithelial cells
- important for T cell homing to the intestinal sites
What extracellular signals in the GI set off the PAMP, PRR (pattern recognition receptor), and transcription factor that lead to Nausea, Fever, & Aches?
- PAMP => LPS, viral proteins, Beta-defensin 2
- PRR => TLR4
- TF => NF-KB
What are four Significant
Pathogen Recognition Receptors in the GI system?
- TLR2 is highly expressed on epithelial cells in the proximal colon, but decreases toward the distal colon. (Gram-positive bacteria, Lipoteichoic acid)
- TLR4 and CD14 is expressed at higher levels in the colon compared to the small intestine. (Gram-negative bacteria, Lipopolysaccharide)
- NOD2 is highly expressed by epithelial cells in the ileum, predominately by Paneth cells. (Muramyl dipeptide and ssRNA)
What is the distribution of lymphoid tissues in the GI system?
- Peyer’s Patchs begin to take form by 11 weeks gestation by appearance of CD4+ DC, and B and T cell regions by 19 weeks gestation
- germinal centers do not appear until after birth
- The PPs appear predominately in the distal ileum containing between 5-200 lymphoid aggregates
- The number of PPs varies with age
- approximately 50 by the beginning of the third trimester, to 100 at birth, rising to 250 in late adolescence, then decreasing to 10 in late years (>70 yrs).
- Other lymphocyte formations appear after birth
- relative density changes in response to inflammatory challenges.
- Isolated Lymphoid Follicle density increases distally through the gut
- 1 ILF per 269 villi in the jejunum, 1 ILF per 28 villi in the ileum,
How does the GI system block entry of a pathogen into the organism (I)?
- Epithelial and mechanical barriers
- Tight junctions (< 2 kDa)
- Trefoil factors (rapid repair of perforations)
- Apical surface of enterocyte forms a selective barrier
- Dense coating of absorptive microvilli
- Layer of Filamentous brush border glycocalyx
- Cilia-mediated expulsion
- Mucins (MUC)
- Product of Goblet Cells
- Neutralizing Antibodies
- Natural Antibodies (IgM and IgG from B1 cells)
- IgA
- Anti-microbial peptides (AMP)
- Leukocytes and Paneth cells produce α-defensins
- Enzymes
- Lysozyme and phospholipase A2 are secreted by Paneth cells
